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Vaginal colonization by fungi may elicit genital inflammation and enhance the risk of adverse reproductive health outcomes, such as HIV acquisition. Cross-sectional studies have linked fungi with an absence of bacterial vaginosis (BV), but it is unclear whether shifts in vaginal bacteria alter the abundance of vaginal fungi. Vaginal swabs collected following topical metronidazole treatment for BV during the phase 2b, placebo-controlled trial of LACTIN-V, a Lactobacillus crispatus-based live biotherapeutic, were assayed with semi-quantitative PCR for the relative quantitation of fungi and key bacterial species and multiplex immunoassay for immune factors. Vaginal fungi increased immediately following metronidazole treatment for BV (adjusted P = 0.0006), with most of this increase attributable to Candida albicans. Vaginal fungi were independently linked to elevated levels of the proinflammatory cytokine interleukin (IL) 17A, although this association did not remain significant after correcting for multiple comparisons. Fungal relative abundance by semi-quantitative PCR returned to baseline levels within 1 month of metronidazole treatment and was not affected by LACTIN-V or placebo administration. Fungal abundance was positively associated with Lactobacillus species, negatively associated with BV-associated bacteria, and positively associated with a variety of proinflammatory cytokines and chemokines, including IL-17A, during and after study product administration. Antibiotic treatment for BV resulted in a transient expanded abundance of vaginal fungi in a subset of women which was unaffected by subsequent administration of LACTIN-V. Vaginal fungi were positively associated with Lactobacillus species and IL-17A and negatively associated with BV-associated bacteria; these associations were most pronounced in the longer-term outcomes.IMPORTANCEVaginal colonization by fungi can enhance the risk of adverse reproductive health outcomes and HIV acquisition, potentially by eliciting genital mucosal inflammation. We show that standard antibiotic treatment for bacterial vaginosis (BV) results in a transient increase in the absolute abundance of vaginal fungi, most of which was identified as Candida albicans. Vaginal fungi were positively associated with proinflammatory immune factors and negatively associated with BV-associated bacteria. These findings improve our understanding of how shifts in the bacterial composition of the vaginal microbiota may enhance proliferation by proinflammatory vaginal fungi, which may have important implications for risk of adverse reproductive health outcomes among women.

Rezafungin is a long-acting, intravenously administered echinocandin for the treatment of candidemia and invasive candidiasis (IC). Non-inferiority of rezafungin vs caspofungin for the treatment of adults with candidemia and/or IC was demonstrated in the Phase 3 ReSTORE study based on the primary endpoints of day 14 global cure and 30-day all-cause mortality. Here, an analysis of ReSTORE data evaluating efficacy outcomes by baseline Candida species is described. Susceptibility testing was performed for Candida species using the Clinical and Laboratory Standards Institute reference broth microdilution method. There were 93 patients in the modified intent-to-treat population who received rezafungin; 94 received caspofungin. Baseline Candida species distribution was similar in the two treatment groups; C. albicans (occurring in 41.9% and 42.6% of patients in the rezafungin and caspofungin groups, respectively), C. glabrata (25.8% and 26.6%), and C. tropicalis (21.5% and 18.1%) were the most common pathogens. Rates of global cure and mycological eradication at day 14 and day 30 all-cause mortality by Candida species were comparable in the rezafungin and caspofungin treatment groups and did not appear to be impacted by minimal inhibitory concentration (MIC) values for either rezafungin or caspofungin. Two patients had baseline isolates with non-susceptible MIC values (both in the rezafungin group: one non-susceptible to rezafungin and one to caspofungin, classified as intermediate); both were candidemia-only patients in whom rezafungin treatment was successful based on the day 30 all-cause mortality endpoint. This analysis of ReSTORE demonstrated the efficacy of rezafungin for candidemia and IC in patients infected with a variety of Candida species.

Candida auris has become a serious threat to public health. The mechanisms of how this fungal pathogen adapts to the mammalian host are poorly understood. Here we report the rapid evolution of an adaptive C. auris multicellular aggregative morphology in the murine host during systemic infection. C. auris aggregative cells accumulate in the brain and exhibit obvious advantages over the single-celled yeast-form cells during systemic infection. Genetic mutations, specifically de novo point mutations in genes associated with cell division or budding processes, underlie the rapid evolution of this aggregative phenotype. Most mutated C. auris genes are associated with the regulation of cell wall integrity, cytokinesis, cytoskeletal properties, and cellular polarization. Moreover, the multicellular aggregates are notably more recalcitrant to the host antimicrobial peptides LL-37 and PACAP relative to the single-celled yeast-form cells. Overall, to survive in the host, C. auris can rapidly evolve a multicellular aggregative morphology via genetic mutations.

Long-term antibiotic treatment results in the increasing resistance of bacteria to antimicrobials drugs, so it is necessary to search for effective alternatives to prevent and treat pathogens that cause diseases. This study is aimed for biological synthesis of silver Carthamus nanoparticles (Ag-Carth-NPs) to combat microbial biofilm formation and Pseudomonas aeruginosa virulence genes. Ag-Carth-NPs are synthesized using Carthamus tenuis aqueous extract as environmentally friendly method has no harmful effect on environment. General factorial design is used to optimize Ag-Carth-NPs synthesis using three variables in three levels are Carthamus extract concentration, silver nitrate concentration and gamma radiation doses. Analysis of response data indicates gamma radiation has a significant effect on Ag-Carth-NPs production. Ag-Carth-NPs have sharp peak at λ max 425 nm, small and spherical particles with size 20.0 ± 1.22 nm, high stability up to 240 day with zeta potential around − 43 ± 0.12 mV, face centered cubic crystalline structure and FT-IR spectroscopy shows peak around 620 cm−1 that corresponding to AgNPs that stabilized by C. tenuis extract functional moiety. The antibacterial activity of Ag-Carth-NPs against pathogenic bacteria and fungi was determined using well diffusion method. The MIC values of Ag-Carth-NPs were (6.25, 6.25, 3.126, 25, 12.5, 12.5, 25 and 12.5 µg/ml), MBC values were (12.5, 12.5, 6.25, 50, 25, 25, 50 and 25 µg/ml) and biofilm inhibition% were (62.12, 68.25, 90.12, 69.51, 70.61, 71.12, 75.51 and 77.71%) against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus, Staphylococcus epidermidis, Candida tropicalis and Candida albicans respectively. Ag-Carth-NPs has bactericidal efficacy and significantly reduced the swarming, swimming motility, pyocyanin and protease production of P. aeruginosa. Furthermore, P. aeruginosa ToxA gene expression was significantly down regulated by 81.5%, while exoU reduced by 78.1%, where lasR gene expression reduction was 68%, while the reduction in exoU was 66% and 60.1% decrease in lasB gene expression after treatment with Ag-Carth-NPs. This activity is attributed to effect of Ag-Carth-NPs on cell membrane integrity, down regulation of virulence gene expression, and induction of general and oxidative stress in P. aeruginosa. Ag-Carth-NPs have no significant cytotoxic effects on normal human cell (Hfb4) but have IC50 at 5.6µg/mL against of HepG-2 cells. Limitations of the study include studies with low risks of silver nanoparticles for in vitro antimicrobial effects and its toxicity. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer, primarily driven by high-risk human papillomavirus (HR-HPV) infection, ranks as the second most common cancer globally. Understanding combined infections' role, including Cervical fungi, is crucial in cervical carcinogenesis. This study aims to explore the potential correlation between HR-HPV, cervical fungi, and cervical cancer, while adjusting for various factors. Methods: The study population comprised patients undergoing colposcopy and conization due to abnormal cervical screening results. Clinical data including age, gravidity, HPV (human papillomavirus) genotypes, cervical pathology, and p16/Ki67 expression were extracted. Cervical TCT (ThinPrep Pap Test) and HPV testing are utilized for screening cervical lesions, with fungal presence suggested by TCT results. 5,528 participants were included in this study. Statistical analyses investigated associations between HPV/fungi co-infection and cervical lesions, employing multinomial logistic regression and interaction analysis. Results: Co-infection with fungi and HPV may decrease the risk of cervical lesions compared to HPV infection alone. In the co-infection group, compared with HPV infection alone, the risk of low-grade squamous intraepithelial lesions (LSIL) was reduced by 27% (OR = 0.73, 95% CI: 0.59-0.90), the risk of high-grade squamous intraepithelial lesions (HSIL) was reduced by 35% (OR = 0.65, 95% CI: 0.51-0.82), and the risk of cervical cancer was reduced by 43% (OR = 0.57, 95% CI: 0.35-0.92). The interaction analysis revealed a negative interaction between fungal and HPV infections in the development of cervical cancer (RERI = lesions compared to HPV infection alone, indicating a novel clinical interaction. Lower p16 positivity in co-infection hints at a protective mechanism, urging further exploration. [ABSTRACT FROM AUTHOR]

Introduction: Translation is a fundamental process of life. In eukaryotes, the elongation step of translation is highly conserved and is driven by eukaryotic translation elongation factors (eEF)1A and eEF2. A significant variation of the elongation is the activity of eukaryotic elongation factor (eEF) 3 in Saccharomyces cerevisiae encoded by the gene yeast elongation factor (YEF3) with orthologs in all fungal species, a few algae, and some protists. In S. cerevisiae, YEF3 is an essential gene and eEF3 plays a critical role in translation elongation, as it promotes binding of the ternary complex acylated-Transfer RNA (tRNA)--eEF1A--Guanosine-5'-triphosphate (GTP) to the aminoacyl (A) site of the ribosome, the release of uncharged tRNAs after peptide translocation, and ribosome recycling. Even though YEF3 was discovered more than 40 years ago, eEF3 has been characterized almost exclusively in S. cerevisiae. Methods: We undertook an in vivo genetic approach to assess the functional conservation of eEF3 across phylogenetically distant fungal species. Results: We found that eEF3 from Zygosaccharomyces rouxii and Candida glabrata (both belonging to phylum Ascomycota), Ustilago maydis (phylum Basidiomycota), and Gonapodya prolifera (phylum Monoblepharomycota), but not Aspergillus nidulans (phylum Ascomycota), supported the growth of S. cerevisiae lacking the endogenous YEF3 gene. We also proved that eEF3 is an essential gene in the ascomycetes C. glabrata and A. nidulans. Discussion: Given that most existing knowledge on fungal translation has only been obtained from S. cerevisiae, our findings beyond this organism showed variability in the elongation process in Fungi. We also proved that eEF3 is essential in pathogenic fungi, opening the possibility of using eEF3 as a target to fight candidiasis. [ABSTRACT FROM AUTHOR]

Our understanding of the spread of yeasts in natural ecosystems remains somewhat limited. The recent momentum of yeast ecology research has unveiled novel habitats and vectors that, alongside human activities, impact yeast communities in their natural environments. Yeasts, as non-airborne microorganisms, rely on animal vectors, predominantly insects. However, the overlooked actor in this interplay is the environmental matrix, a player potentially influencing yeast populations and their vectors. This study aims to delve deeper into the intricate, multi-layered connections between yeast populations and ecosystems, focusing on the interactions between the attributes of the environmental matrix, arthropod diversity, and the mycobiota within a renowned yeast-inhabited framework: the vineyard. To investigate these relationships, we sampled both invertebrate and yeast diversity in six organic and conventional vineyards described in terms of management and landscape composition. We identified 80 different invertebrate taxa and isolated 170 yeast strains belonging to 18 species. Notably, new species-specific yeast-insect associations were observed, including the exclusive association between Candida orthopsilosis and Hymenoptera and between Metschnikowia pulcherrima and Coleoptera. These newly identified potential associations provide valuable insights into insect and yeast physiology, hence holding the promise of enhancing our understanding of yeast and arthropod ecology and their collective impact on overall ecosystem health. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is globally recognized as a significant health concern, with diabetic foot (DF) identified as a severe long-term complication that can lead to tissue death or amputation. The discovery of the impact of mycobiota, a diverse group of multicellular eukaryotes in the gut microbiome, on the onset of endocrine disorders holds great significance. Therefore, this research aimed to examine variations in fungal mycobiome and identify potential biomarkers for T2DM and T2DM-DF. Fecal and blood samples were collected from 33 individuals with T2DM, 32 individuals with T2DM-DF, and 32 healthy individuals without any health conditions (HC). Blood samples were used for laboratory parameters analysis, while total DNA was extracted from fecal samples and sequenced using Illumina 18s rRNA. Bioinformatics tools were employed to analyze fungal abundance and diversity, revealing differentially expressed fungal species and signature fungi that distinguished between T2DM, T2DM-DF, and HC groups. Firstly, significant alterations in some laboratory parameters were observed among the three groups, which also differed between T2DM and T2DM-DF. The diversity of gut fungi in T2DM and T2DM-DF significantly differed from that of the HC group; however, more pronounced changes were observed in T2DM-DF. Additionally, two significantly altered phyla, Ascomycota and Basidiomycota, were identified with higher Ascomycota abundance but lower Basidiomycota abundance in both the T2DM and T2DM-DF compared to the HC group. Furthermore, the top 15 fungi showing significant changes at the species level included a notable decrease in Rhodotorula_mucilaginosa abundance in patients with T2DM compared to HC and a substantial increase in unclassified_g_Candida abundance specifically seen only among patients with T2DM-DF, but not among those diagnosed with T2DM or HC. Thirdly, KEGG was employed to analyze enzyme expression across the three groups, revealing a more pronounced alteration in gut fungal function within T2DM-DF compared to T2DM. Subsequently, to accurately identify signature fungi in each group, a random forest was utilized to rank the top 15 significant fungi. Notably, 11 fungi were identified as potential biomarkers for distinguishing T2DM or T2DM-DF from HC, while eight fungi could discriminate between T2DM and T2DM-DF. Furthermore, receiver operating characteristic curve (ROC) analysis demonstrated enhanced accuracy of predicted outcomes. These findings suggest that changes in fungal mycobiome are closely associated with the progression and complications of T2DM and DF, offering promising prospects for diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Azole resistance in the pathogenic yeast Candida glabrata is a serious clinical complication and increasing in frequency. The majority of resistant organisms have been found to contain a substitution mutation in the Zn2Cys6 zinc cluster-containing transcription factor Pdr1. These mutations typically lead to this factor driving high, constitutive expression of target genes like the ATP-binding cassette transporter-encoding gene CDR1. Overexpression of Cdr1 is required for the observed elevated fluconazole resistance exhibited by strains containing one of these hyperactive PDR1 alleles. While the identity of hyperactive PDR1 alleles has been extensively documented, the mechanisms underlying how these gain-of-function (GOF) forms of Pdr1 lead to elevated target gene transcription are not well understood. We have used a tandem affinity purification-tagged form of Pdr1 to identify coactivator proteins that biochemically purify with the wild-type and 2 different GOF forms of Pdr1. Three coactivator proteins were found to associate with Pdr1: the SWI/SNF complex Snf2 chromatin remodeling protein and 2 different components of the SAGA complex, Spt7 and Ngg1. We found that deletion mutants lacking either SNF2 or SPT7 exhibited growth defects, even in the absence of fluconazole challenge. To overcome these issues, we employed a conditional degradation system to acutely deplete these coactivators and determined that loss of either coactivator complex, SWI/SNF or SAGA, caused defects in Pdr1-dependent transcription. A double degron strain that could be depleted for both SWI/SNF and SAGA exhibited a profound defect in PDR1 autoregulation, revealing that these complexes work together to ensure high-level Pdr1-dependent gene transcription. [ABSTRACT FROM AUTHOR]

• The most susceptible pathogens tested were Candida glabrata and C. tropicalis. • The n-hexane fraction had the highest antimicrobial activity (0.06 – 0.25 mg/mL). • Cidal effects against C. glabrata (of 0.06 mg/mL hexane fraction, at 5 mins). • Major active compounds include methyl linolenate, n-hexadecanoic acid and phytol. • Time-kill results were favorably comparative to the antifungal Nystatin. Species of the genus Leonotis (Lamiaceae) are commonly used in Africa as traditional herbal remedies for various ailments such as bronchial illness, epilepsy, stomach aches, and skin diseases. Most of these species are found in South Africa, and Leonotis ocymifolia (Burm.f.) Iwarsson (klipdagga) is one of them. The recorded medicinal uses of L. ocymifolia include treating diabetes, hypertension, anemia, nerve weakness, high blood pressure, poor blood circulation, rheumatism, snakebites, eczema, and several skin infections among others. Little is known about the antimicrobial activity. Therefore, this study aimed to investigate the antimicrobial potential of L. ocymifolia by reviewing the ethnomedicinal importance and antimicrobial potential (Minimum Inhibitory Concentration, Minimum bactericidal concentration, and Time-kill assessment) as well as the toxicity of L. ocymifolia 's extracts (DCM: Meth) and fractions (ethyl acetate, hexane, and butanol) against six bacteria and four Candida species. The results demonstrated that all the Candida pathogens tested were susceptible to the extracts, with moderate to noteworthy activity. The n -hexane fraction exhibited the highest antimicrobial activity against all tested pathogens, with mean MIC values between 0.06 – 0.25 mg/mL. Moderate activity was observed for the extracts against the bacteria tested, except for Klebsiella pneumoniae , where noteworthy activity (MIC value of 0.13 mg/mL) was found for the n -butanol fraction. A cidal effect on C. glabrata was recorded by the n -butanol fraction at 1xMIC (0.13 mg/mL) after 30 min of contact time and after 60 min at 1/2xMIC which is better than the positive control (Nystatin) where the cidal effect was only recorded after 4 h of contact time at 0.13 mg/mL. The hexane fraction was subjected to chemical analysis (gas chromatography-mass spectrometry) because of the noteworthy anticandidal activity. Nineteen compounds were identified with major compounds including methyl linolenate (33.31 %), n -hexadecanoic acid (21.32 %), phytol (21.35 %), and octadecenoic acid methyl ester (4.87 %). Leonotis ocymifolia has demonstrated promising antimicrobial properties, particularly against Candida species where the cidal effects link to the possible traditional use for Candida -acquired skin infections. The findings of this study, as determined by the brine shrimp lethality assay, indicate that usage of this plant extract poses minimal risk. [ABSTRACT FROM AUTHOR]

Oral fungal infections pose a threat to human health and increase the economic burden of oral diseases by prolonging and complicating treatment. A cost-effective strategy is to try to prevent these infections from happening in the first place. With this purpose, biomaterials with antifungal properties are a crucial element to overcome fungal infections in the oral cavity. In this review, we go through different kinds of biomaterials and coatings that can be used to functionalize them. We also review their potential as a therapeutic approach in addition to prophylaxis, by going through traditional and alternative antifungal compounds, e.g., essential oils, that could be incorporated in them, to enhance their efficacy against fungal pathogens. We aim to highlight the potential of these technologies and propose questions that need to be addressed in prospective research. Finally, we intend to concatenate the key aspects and technologies on the use of biomaterials in oral health, to create an easy to find summary of the current state-of-the-art for researchers in the field. [ABSTRACT FROM AUTHOR]

Candida species is one of the pathogenic fungi of the eye responsible for keratitis that frequently causes vision impairment and blindness. Effective treatment requires long-term use of antifungal drugs, which is opposed by the defensive mechanisms of the eye and inadequate corneal penetration. The objective of this study was to develop a carrier for prolonged ocular application of fluconazole (FLZ) to treat keratitis. FLZ was encapsulated into chitosan fibrous matrices (F1–F4) using different chitosan concentrations (0.02, 0.1, 0.5, and 1%w/v, respectively) by freeze-drying as a single-step technique. Studying the morphology and surface properties of the inserts revealed a porous matrix with fibrous features with a large surface area. Thermal stability and chemical compatibility were confirmed by DSC/TGA/DTA and FT-IR, respectively. Loading capacity (LC) and entrapment efficiency (EE) were determined. According to the in vitro release study, F4 (0.11 mg mg−1 LC and 87.53% EE) was selected as the optimum insert because it had the most sustained release, with 15.85% burst release followed by 75.62% release within 12 h. Ex vivo corneal permeation study revealed a 1.2-fold increase in FLZ permeation from F4 compared to FLZ aqueous solution. Also, in the in vivo pharmacokinetic study in rabbits, F4 increased the AUC0-8 of FLZ by 9.3-fold and its concentration in aqueous humor was maintained above the MIC through the experimentation time. Studies on cytotoxicity (MTT assay) provide evidence for the safety and biocompatibility of F4. Therefore, the freeze-dried FLZ-loaded chitosan fibrous insert could be a promising candidate for treating ocular keratitis. [ABSTRACT FROM AUTHOR]

Methanol is a promising feedstock for biomanufacturing, but the efficiency of methanol-based bioprocesses is limited by the low rate of methanol utilization pathways and methanol toxicity. Yeast diversity is an attractive biological resource to develop efficient bioprocesses since any effort with strain improvement is more deserving if applied to innate robust strains with relevant catabolic and biosynthetic potential. The present study is in line with such rational and describes the isolation and molecular identification of seven isolates of the methylotrophic species Candida boidinii from waters derived from the traditional curation of olives, in different years, and from contaminated superficial soil near fuel stations. The yeast microbiota from those habitats was also characterized. The four C. boidinii isolates obtained from the curation of olives' water exhibited significantly higher maximum specific growth rates (range 0.15–0.19 h−1), compared with the three isolates obtained from the fuel contaminated soils (range 0.05–0.06 h−1) when grown on methanol as the sole C-source (1% (v/v), in shake flasks, at 30°C). The isolates exhibit significant robustness towards methanol toxicity that increases as the cultivation temperature decreases from 30°C to 25°C. The better methanol-based growth performance exhibited by C. boidinii isolates from olives´ soaking waters could not be essentially attributed to higher methanol tolerance. These methanol-efficient catabolizing isolates are proposed as a promising platform to develop methanol-based bioprocesses. [ABSTRACT FROM AUTHOR]

Introduction: Klebsiella pneumoniae (K. pneumoniae) is the most common pathogen causing hospital respiratory tract infection and epidemic. Gold standard procedures of microscopic examination and biochemical identification are widely used in clinical diagnosis with disadvantages of low sensitivity, time-consuming and sophisticated equipment requiring. An efficient, nucleic acid amplification-based sensitive and specific on-site identification of K. pneumoniae in clinical is necessary to facilitate clinical medication and disease control. Methods: We developed a closed dumbbell mediated isothermal amplification (CDA) assay for the rapid and sensitive detection of conserved rcsA gene in K. pneumoniae by real-time fluorescence monitoring and end-point colorimetric judgement. We designed and selected a pair of inner primers of CDA to detect K. pneumoniae. Then outer and loop primers were designed and verified to accelerate CDA reaction to achieve more efficient detection of K. pneumoniae. Results: The results showed the detection limit of CDA assay was 1.2x10-5 ng/μL (approximately 1 copy of the target gene) within 60 min, which was 100-fold more sensitive than real-time quantitative PCR (qPCR). Several pathogen genomic DNAs (Staphylococcus aureus, Shigella sonnei, Vibrio parahaemolyticus, Escherichia coli, Candida glabrata, Candida tropicalis, Candida parapsilosis, Candida albicans, Streptococcus agalactiae, Rickettsia, Listeria monocytogenes, Pseudomonas aeruginosa, Klebsiella oxytoca, and Klebsiella aerogenes) were used to evaluate the sensitivity and specificity of the established K. pneumoniae CDA assay. Total 224 batches of samples from other strains tested were negative and 296 batches of extracted K. pneumoniae DNA samples were positive by the developed CDA amplification approach, revealing high specificity and specificity of the diagnostic assay. In addition, the results of real-time fluorescence amplification of the K. pneumoniae CDA were in consistent with those of end-point colorimetric results. Discussion: The established real-time fluorescence and visual CDA assays of K. pneumoniae with merits of rapid, sensitive and specificity could be helpful for on-site diagnosis and clinical screening in rural areas. [ABSTRACT FROM AUTHOR]

Sugarcane smut, caused by the fungus Sporisorium scitamineum (Sydow), significantly affects sugarcane crops worldwide. Infected plants develop whip-like structures known as sori. Significant variations in these whip lengths are commonly observed, but the physiological and molecular differences causing these morphological differences remain poorly documented. To address this, we employed conventional microbe isolation, metagenomic, and metabolomic techniques to investigate smut-infected sugarcane stems and whips of varying lengths. Metagenomics analysis revealed a diverse fungal community in the sugarcane whips, with Sporisorium and Fusarium genera notably present (>1%) in long whips. Isolation techniques confirmed these findings. Ultra-performance liquid chromatography analysis (UHPLC-MS/MS) showed high levels of gibberellin hormones (GA3, GA1, GA4, GA8, and GA7) in long whips, with GA4 and GA7 found exclusively in long whips and stems. Among the prominent genera present within long whips, Fusarium was solely positively correlated with these gibberellin (GA) hormones, with the exception of GA8, which was positively correlated with Sporisorium. KEGG enrichment analysis linked these hormones to pathways like diterpenoid biosynthesis and plant hormone signal transduction. These findings suggest that Fusarium may influence GA production leading to whip elongation. Our study reveals fungal dynamics and gibberellin responses in sugarcane smut whips. Future research will explore the related molecular gibberellin synthesis mechanisms. [ABSTRACT FROM AUTHOR]

Noncovalent interactions associated with the enzyme, enzyme-substrate complexes, and transition states have profound influences on varying the biocatalytical activity and enantioselectivity. The recent rediscovery of halogen bonds incorporating in biocatalysis has induced our motivation on introducing halogen substituents into the substrate for improving the enzyme performance. By selecting Candida antarctica lipase B (CALB)-catalyzed kinetic hydrolysis (or butanolysis) of trans-2-(p-halophenyl)cyclopropyl 1,2,4-triazolide in methyl tert-butyl ether (MTBE) as the model reaction system, (R, R)-2-(p-halophenyl)cyclopropane-1-carboxylic acid (or ester) of high-optical purity that acts as the key building block for synthesizing the corresponding (1 R, 2S)-2-(p-halophenyl)cyclopropylamine derivatives was obtainable. The thermodynamic and kinetic analysis was then employed for elucidating effects of the halogen substituent and acyl acceptor on enhancing the noncovalent interactions of the rate-limiting tetrahedral intermediate and hence CALB activity and enantioselectivity. A putative model was moreover proposed for interpreting the possible hydrogen and halogen bonding involving the halogen substituent in turning the noncovalent interactions. [ABSTRACT FROM AUTHOR]

Emerging and uncommon Candida species have been reported as an increasing cause of invasive Candida infections (ICI). We aim to systematize the global epidemiology associated with emergent uncommon Candida species responsible for invasive infections in adult patients. A systematic review (from 1 January 2001 to 28 February 2023) regarding epidemiological, clinical, and microbiological data associated to invasive Candida infections by uncommon Candida spp. were collected. In total, 1567 publications were identified, and 36 were selected according to inclusion criteria (45 cases). The chosen studies covered: C. auris (n = 21), C. haemulonii (n = 6), C. fermentati (n = 4), C. kefyr (n = 4), C. norvegensis (n = 3), C. nivariensis (n = 3), C. bracarensis (n = 1), C. duobushaemulonii (n = 1), C. blankii (n = 1), and C. khanbhai (n = 1). Over the recent years, there has been an increase in the number of invasive infections caused by uncommon Candida spp. Asia and Europe are the continents with the most reported cases. The challenges in strain identification and antifungal susceptibility interpretation were significant. The absence of clinical breakpoints for the susceptibility profile determination for uncommon Candida spp. makes interpretation and treatment options a clinical challenge. It is crucial that we focus on new and accessible microbiology techniques to make fast and accurate diagnostics and treatments. [ABSTRACT FROM AUTHOR]

Cyclodextrins, commonly used as excipients in antifungal formulations to improve the physicochemical properties and availability of the host molecules, have not been systematically studied for their effects and bioactivity without a complex active substance. This paper evaluates the effects of various cyclodextrins on the physiology of the test organism Candida boidinii. The research examines their impact on yeast growth, viability, biofilm formation and morphological changes. Native ACD, BCD, randomly methylated α- and β-CD and quaternary ammonium α-CD and β-CD were investigated in the 0.5–12.5 mM concentration range in both static and dynamic systems. The study revealed that certain cyclodextrins exhibited notable antifungal effects (up to ~69%) in dynamic systems; however, the biofilm formation was enhanced in static systems. The magnitude of these effects was influenced by several variables, including the size of the internal cavity, the concentration and structure of the cyclodextrins, and the contact time. Furthermore, the study found that CDs exhibited distinct effects in both static and dynamic systems, potentially related to their tendency to form aggregates. The findings suggest that cyclodextrins may have the potential to act as antifungal agents or growth promoters, depending on their structure and surrounding environments. [ABSTRACT FROM AUTHOR]

Fungal pathogens have a major, yet greatly underappreciated, impact on global human health, infecting billions and killing more than 3.75 million individuals each year. Over the past few decades, the discovery of novel antifungals for therapeutic development has been limited, with only three main antifungal classes available to treat systemic fungal infections: polyenes, azoles, and echinocandins. Fortunately, the deployment of interdisciplinary approaches for antifungal discovery is yielding breakthroughs in drug development that have not been seen in decades. Improvements to current antifungals, discovery of novel compound combinations, structure-guided approaches, and functional genomic screening to identify novel cellular targets are all important in expanding the antifungal armamentarium. Pathogenic fungi are an increasing public health concern. The emergence of antifungal resistance coupled with the scarce antifungal arsenal highlights the need for novel therapeutics. Fortunately, the past few years have witnessed breakthroughs in antifungal development. Here, we discuss pivotal interdisciplinary approaches for the discovery of novel compounds with efficacy against diverse fungal pathogens. We highlight breakthroughs in improving current antifungal scaffolds, as well as the utility of compound combinations to extend the lifespan of antifungals. Finally, we describe efforts to refine candidate chemical scaffolds by leveraging structure-guided approaches, and the use of functional genomics to expand our knowledge of druggable antifungal targets. Overall, we emphasize the importance of interdisciplinary collaborations in the endeavor to develop innovative antifungal strategies. [ABSTRACT FROM AUTHOR]

Background and Objectives: Fungal burn wound infections (FBWIs) are one of the most disastrous complications in burn patients. The present study investigated the incidence and the species distribution of fungal agents isolated from burn lesions and reviewed the feautures, underlying conditions, and outcomes of patients. Materials and Methods: The wounds were swabbed and cultured on Sabouraud Dextrose Agar with chloramphenicol medium. Fungal identification was performed using internal transcribed spacer (ITS) and beta-tubulin sequencing. Results: A total of 380 swab specimens were obtained. Of these, 101 patients (26.75 %) were positive in culture. Among the 101 positive cases, most isolates were from males (n= 68, 67.33%) and most of them were over 30 years old. Flame (n=38, 37.63%) was the predominant cause of burns, and previous history of ICU admission (n=35, 34.66%), presence of central venous catheter (n=25, 24.75%), and diabetes mellitus (n=17, 16.83%) were the main underlying conditions. Candida parapsilosis complex (n=36, 35.64%), and Pichia kudriavzevii (C. krusei) (n=8, 7.92%) represent the most commonly isolated species Also, 2 out of 101 patients (2%) died. Conclusion: In the present study, non-albicans Candida species were much higher frequent than C. albicans with most cases associated with Candida parapsilosis complex. [ABSTRACT FROM AUTHOR]

Oral candidiasis is a common problem among immunocompetent patients. The frequent resistance of Candida strains to popular antimycotics makes it necessary to look for alternative methods of treatment. The authors conducted a systematic review following the PRISMA 2020 guidelines. The objective of this review was to determine if curcumin-mediated blue light could be considered as an alternative treatment for oral candidiasis. PubMed, Google Scholar, and Cochrane Library databases were searched using a combination of the following keywords: (Candida OR candidiasis oral OR candidiasis oral OR denture stomatitis) AND (curcumin OR photodynamic therapy OR apt OR photodynamic antimicrobial chemotherapy OR PACT OR photodynamic inactivation OR PDI). The review included in vitro laboratory studies with Candida spp., in vivo animal studies, and randomized control trials (RCTs) involving patients with oral candidiasis or prosthetic stomatitis, published only in English. The method of elimination of Candida species in the studies was curcumin-mediated aPDT. A total of 757 studies were identified. Following the analysis of the titles and abstracts of the studies, only 42 studies were selected for in-depth screening, after which 26 were included in this study. All studies evaluated the antifungal efficacy of curcumin-mediated aPDT against C. albicans and non-albicans Candida. In studies conducted with planktonic cells solutions, seven studies demonstrated complete elimination of Candida spp. cells. The remaining studies demonstrated only partial elimination. In all cases, experiments on single-species yeast biofilms demonstrated partial, statistically significant inhibition of cell growth and reduction in biofilm mass. In vivo, curcumin-mediated aPDT has shown good antifungal activity against oral candidiasis also in an animal model. However, its clinical efficacy as a potent therapeutic strategy for oral candidiasis requires few further RCTs. [ABSTRACT FROM AUTHOR]

Knowledge about voice prosthesis microbial colonization is vital in laryngectomized patients' quality of life (QoL). Herein, we aimed to explore the relationship between oral microbial patterns, demographic variables and voice prosthesis performance. Thirty laryngectomy patients were assessed for microbial colonization in their voice prostheses and oral cavities. Factors like age, proton pump inhibitor (PPI) usage, and alcohol consumption were considered. Participants' average age was 74.20 ± 7.31 years, with a majority on PPIs. Staphylococcus aureus was the most common bacterium in prostheses (53 %), followed by Pseudomonas aeruginosa (27 %). Candida albicans was the primary fungal colonizer (67 %). A statistically significant moderate correlation was found between fungal species before and after oral rinsing (p = 0.035, Phi=0.588, Cramer's V = 0.416). Voice prosthesis and oral cavity microbiota profiles showed significant concordance (kappa=0.315, p < 0.004). Among subgroup analyses, bacterial patterns of colonization did not significantly influence VHI (p = 0.9555), VrQoL (p = 0.6610), or SF-36 (p = 0.509) scores. Conversely, fungal patterns of VP colonization significantly impacted subjective voice scores, with Candida krusei demonstrating better VHI (35.25 ± 3.63 vs. 44.54 ± 6.33; p = 0.008), VrQoL (7.13 ± 1.69 vs. 10.73 ± 2.00; p = 0.001), and SF-36 (69.36 ± 7.09 vs. 76.50 ± 7.73; p = 0.051) scores compared to C. albicans. There was a significant correlation between the oral microbiota and voice prosthesis colonization. These insights can inform improved care strategies for voice prostheses, enhancing patient outcomes. [ABSTRACT FROM AUTHOR]

To understand retina specialists' attitudes and practice patterns for screening for and managing Candida endophthalmitis and any impact of the COVID-19 pandemic on these practice patterns. A survey was developed on Survey Monkey and distributed to ASRS regular members via email in April 2021. The survey had 231 respondents, of whom 169 (73%) performed inpatient consultations. Ninety percent responded that they do not recommend routinely screening asymptomatic patients with candidemia. For unresponsive patients with candidemia that lack visible signs of endophthalmitis, 65% did not recommend routine screening. However, 85% reported their affiliated hospitals did not have a policy to defer such screening consultations; this proportion did not significantly change when asked if a policy was implemented in response to the COVID-19 pandemic. For patients with a dilated examination without signs of endophthalmitis, 89% surveyed recommended continuing systemic antifungals and reconsult PRN, while the remainder recommended repeat examinations until off antifungals. For initial management of Candida endophthalmitis, 55% indicated systemic antifungals only; 43% indicated systemic antifungals with tap & inject, and 2% indicated systemic antifungals with vitrectomy and intravitreal antifungals. A discordance exists between the prevailing opinion among retina specialists against routine Candida endophthalmitis screening and hospital consultation policies, which were not significantly impacted by the COVID-19 pandemic. In cases of diagnosed endogenous endophthalmitis, slightly more than half of surveyed retina specialists would not initiate additional treatment beyond systemic antifungals while just under half surveyed recommended initial tap and inject in addition to systemic antifungals. [ABSTRACT FROM AUTHOR]

Candida endophthalmitis is a severe complication of candidemia. Currently, the recommended treatment of fungal endophthalmitis is a combination of intravitreal and systemic antifungal drugs, and in some cases vitrectomy is also required. Intravitreal therapies that are commonly used are amphotericin B and voriconazole, although recently the use of intravitreal caspofungin has been described in a few case reports. However, clinical experience with intravitreal caspofungin is still limited. We report a case of bilateral candida tropicalis endophthalmitis, initially managed with repeated 100 μg/0.1 ml caspofungin intravitreal injections and posteriorly treated with pars plana vitrectomy in both eyes. Intravitreal caspofungin could be a safe intravitreal alternative to habitual antimycotic drugs in cases with resistant candida endophthalmitis.Abbreviations: Intensive Care Unit (ICU); Best-Corrected Visual Acuity (BCVA) [ABSTRACT FROM AUTHOR]

Clavispora lusitaniae has been isolated from different substrates, such as soil, water, fruit, vegetables, plants, and the gastrointestinal tract of animals and humans. However, its importance lies in being isolated from in invasive infections, particularly in pediatric patients with hematologic malignancies. It is an emerging nosocomial pathogen commonly associated with fatal prognosis in immunocompromised hosts. C. lusitaniae has attracted attention in the last decade because of resistance to amphotericin B, 5- flucytosine, and fluconazole. The adaptations of this yeast to the human host may contribute to its pathogenicity. Further study will be needed to understand C. lusitaniae 's ability as a potential pathogen. This mini-review highlights the importance of the growing number of invasive disease cases caused by this yeast. • Clavispora lusitaniae has been isolated from the environment and human microbiota. • C. lusitaniae produces invasive infections in immunosuppressed patients. • C. lusitaniae antifungal resistance is associated to treatment failure. • C. lusitaniae should be considered an emerging health threat. [ABSTRACT FROM AUTHOR]

Purpose: Candida auris, an emerging multidrug-resistant yeast, has been reported worldwide. In Italy, the first case was reported in 2019. We describe the first case of C. auris, imported from Greece, in Milan, using whole genome sequencing to characterise mutations associated with antifungal resistance. Case presentation: On October 2022 an 80-year-old Italian man was hospitalised in Greece. In the absence of clinical improvement, the patient was transferred to our hospital, in Italy, where blood culture resulted positive for C. auris. Despite therapy, the patient died of septic shock. In a phylogenetic analysis the genome was assigned to Clade I with strains from Kenya, United Arab Emirates and India. D1/D2 region resulted identical to a Greek strain, as for many other strains from different World regions, highlighting the diffusion of this strain. Conclusion: Importation of C. auris from abroad has been previously described. We report the first case of C. auris imported into Italy from Greece, according to phylogenetic analysis. This case reinforces the need for monitoring critically ill hospitalised patients also for fungi and addresses the need for the standardisation of susceptibility testing and strategies for diagnosis and therapy. [ABSTRACT FROM AUTHOR]

Green nanotechnology is one of the most expanding fields that provides numerous novel nanoparticle drug formulations with enhanced bioactivity performance. This study aims to synthesize mesoporous metal organic framework (ZIF-8) phytofabricated with the herb Allium sativum (As) as an indicator system for its antibacterial and antifungal impact. The successful synthesis of ZIF-8 as nanocomposite was characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and scanning coupled with energy-dispersive X-ray spectroscopy and transmission electron microscopy (SEM–EDX and TEM) that showed the textural retainment of ZIF-8 on composite formation with A. sativum. The nanocomposite, A. sativum extract, and ZIF-8 were subjected to antimicrobial assays against Shigella flexneri, Candida albicans, and Candida parapsilosis. The comparative results indicated the potential action of nanocomposite against the bacteria and both the Candida sps; however, the antifungal action against the Candida sps was more effective than the bacterium S. flexneri. The findings suggest that plants, being an important component of ecosystems, could be further explored for the novel drug discovery using green nanotechnology to enhance their impact on the drug-resistant pathogens. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to determine the antifungal activity of olive leaf extract (OLE) and the synergistic effect of standard antifungal therapy and OLE against clinical oral Candida species' isolates. Materials and Method: The susceptibility of 60 clinical isolates of the Candida species (36 C. albicans, 16 C. krusei, 5 C. glabrata and 3 C. tropicalis) was tested with four concentrations of OLE (60 µg/µL, 120 µg/µL, 240 µg/µL and 333 µg/µL) and the synergistic effect of standard antifungal therapy and OLE (miconazole (MIC) + 333 µg/µL OLE and nystatin (NYS) + 333 µg/µL OLE). The antimicrobial activity was tested using the disk diffusion method. Results: All concentrations (60 µg/µL, 120 µg/µL, 240 µg/µL and 333 µg/µL) of OLE showed a statistically significant effect on all Candida species compared to the control (DMSO) except for the lowest concentration (60 µg/µL) tested on C. glabrata. There was a dose-dependent effect of OLE on tested samples. Concentrations of 240 µg/µL and 333 µg/µL showed statistically significant higher antifungal activity compared to the lowest concentration of 60 µg/µL. No statistically significant synergistic effect of OLE and standard antifungal therapy was found compared with standard therapy alone. Conclusions: The results of this study present the significant antimicrobial effect of OLE against all tested Candida species except for the lowest concentration on C. glabrata. Increasing the concentration of OLE also increases its effect on Candida species. This indicates the possible potential effect of OLE in the treatment of Candida-related oral diseases. [ABSTRACT FROM AUTHOR]

Fungal keratitis is a rare yet severe infection of the cornea. Fungal species distribution depends on the climate and socioeconomic status and can show regional variation. This retrospective single-center study was conducted at a tertiary eye care center and the collaborating Institute of Medical Microbiology in Switzerland. On investigating all fungal-positive corneal scrapings and contact lens assessments of patients with keratitis from January 2012 to December 2023, 206 patients were identified, of which 113 (54.9%) were female. The median age was 38 (IQR 29.8, [18–93]), and 154 (74.8%) applied contact lenses. The most commonly found pathogen was Candida spp., followed by Fusarium spp. Molds were 1.8 times more common than yeasts. Linear regression showed no significant increase or decrease in the infection rate over time (p = 0.5). In addition, 10 patients (4.9%) were found to have coinfections with Acanthamoeba, 11 (5.3%) with HSV-1, none with HSV-2, and 4 (1.9%) with VZV. This study provides a long-term overview of fungal-positive corneal scrapings and contact lens specimens of patients with fungal keratitis. Based on our results, coinfections with Acanthamoeba, HSV, and VZV are frequent, especially in patients wearing contact lenses. Thus, wearing contact lenses may facilitate coinfection in fungal keratitis. [ABSTRACT FROM AUTHOR]

Probiotics are living microbes that provide benefits to the host. The growing data on health promotion, following probiotics administration, increased interest among researchers and pharmaceutical companies. Infections of the lower genital tract in females, caused by a wide range of pathogens, represent one of the main areas for the use of probiotics and postbiotics. Vulvovaginal candidiasis (VVC) affects 75% of women of reproductive age at least once during their lifetime, with 5–8% developing the recurrent form (RVVC). The disease is triggered by the overgrowth of Candida on the vaginal mucosa. Here, in order to establish its probiotic potential in the context of VVC, we evaluated the anti-fungal effects of the spore-producing Bacillus coagulans LMG S-24828 against C. albicans and C. parapsilosis as well as its beneficial effects in counteracting Candida vaginal infection in vitro. Our results show that both live B. coagulans and its Cell-Free Supernatant (CFS) exerted antifungal activity against both fungi. Moreover, live B. coagulans reduced hyphal formation, inhibited C. albicans adhesion to vaginal epithelial cells, showed co-aggregation capacity, and exerted a protective effect on vaginal epithelial cells infected with C. albicans. These data suggest that B. coagulans LMG S-24828 may provide benefits in the context of Candida vaginal infections. [ABSTRACT FROM AUTHOR]

Invasive candidiasis and candidemia remain a significant public health concern. The European Confederation of Medical Mycology (ECMM) conducted three pan-European multicentre studies from 1997 to 2022 to investigate various aspects of invasive Candida infections. These studies revealed shifting trends in Candida species distribution, with an increase of non-albicans Candida species as causative pathogens, increasing rates of antifungal resistance, and persistently high mortality rates. Despite advancements in antifungal treatment, the persistently high mortality rate and increasing drug resistance, as well as limited drug access in low-income countries, underscore the need for continued research and development in the treatment of Candida infections. This review aims to summarize the findings of the three completed ECMM Candida studies and emphasize the importance of continued research efforts. Additionally, it introduces the upcoming ECMM Candida IV study, which will focus on assessing candidemia caused by non-albicans Candida species, including Candida auris, investigating antifungal resistance and tolerance, and evaluating novel treatment modalities on a global scale. [ABSTRACT FROM AUTHOR]

This article presents a case study of a 59-year-old female diabetic patient who developed an invasive vesical Candida infection causing ureteric obstruction. Fungal balls in the urinary bladder are rare and typically associated with diabetes. The patient underwent surgical resection of the fungal mass and received systemic antifungal therapy. Prompt management resulted in a rapid recovery, and the patient has remained infection-free. The article emphasizes the importance of a multidisciplinary approach involving urologists, infectious disease physicians, and microbiologists in the treatment of invasive Candida infections. [Extracted from the article]

Background: NETs, a unique neutrophil immune mechanism, are vital in defending against microbial invasions. Understanding the mechanisms of coinfection by Candida albicans and Staphylococcus aureus, which often leads to higher mortality and poorer prognosis, is crucial for studying infection progression. Methods: In our study, we established a mouse model of subcutaneous infection to characterize the inflammation induced by co-infection. By purifying and extracting NETs to interact with microorganisms, we delve into the differences in their interactions with various microbial species. Additionally, we investigated the differences in NETs production by neutrophils in response to single or mixed microorganisms through the interaction between neutrophils and these microorganisms. Furthermore, we analyzed the gene expression differences during co-infection using transcriptomics. Results: In vivo, C. albicans infections tend to aggregate, while S. aureus infections aremore diffuse. In cases of co-infection, S. aureus adheres to and wraps C. albicans. NETs exhibit strong killing capability against C. albicans butweaker efficacy against S. aureus. When NETs interact with mixed microorganisms, they preferentially target and kill the outer layer of S. aureus. In the early stages, neutrophils primarily rely on phagocytosis to kill S. aureus, but as the bacteria accumulate, they stimulate neutrophils to produce NETs. Interestingly, in the presence of neutrophils, S. aureus promotes the proliferation and hyphal growth of C. albicans. Conclusion: Our research has showed substantial differences in the progression of co-infections compared to single-microbial infections, thereby providing scientific evidence for NETs as potential therapeutic targets in the treatment of co-infections. [ABSTRACT FROM AUTHOR]

Sclerotinia rot is a serious disease that occurs on Zephyranthes candida. A thorough understanding of the pathogenic fungal species and understanding the biological characteristics are important for controlling sclerotinia. Fungal strains were isolated from the diseased leaves of Z. candida through tissue isolation. Koch's hypothesis screened pathogenic strains by pathogenicity of healthy leaves, including re-isolation and identification. A multigene phylogenetic tree was constructed by extracting genomic DNA from pathogenic strains and measuring the nucleotide sequences at four sites, including the internal transcribed spacer (ITS), RNA polymerase II second largest subunit (RPB2), glyceraldehyde-3-phosphate dehydrogenase (G3PDH), and heat shock protein 60 (HSP60). Morphological characteristics of the fungal structures were evaluated through microscopic analysis. The growth of pathogens was observed and recorded under different pH, different temperatures, different carbon sources and different nitrogen sources to clarify their biological characteristics. Representative strains D7, D13, X4, and X15 infected Z. candida and caused sclerotinia rot. At the beginning of the culture, white flocculent fungal hyphae appeared on the potato dextrose agar (PDA) medium, and black spherical to irregular-shaped sclerotia appeared at the edge of the colony after 7 days. The diameter of the sclerotia was 2.4-8.6 mm and 0.4-0.9 mm, respectively. One sclerotium was able to germinate from 1 to 5 apothecia. Ascus were cylindrical or spindle-shaped, with a size of 110.0-120.0 x 9.2-11.6 μm. One ascus contained eight colorless, oval ascospores, with a size of 8.4-12.0 x 4.5-5.5 μm. Based on the phylogenetic tree constructed with the gene sequences for ITS, G3PDH, HSP60, and RPB2, D7 and D13 shared 99% homology with sclerotinia sclerotiorum, whereas X4 and X15 shared 99% homology with sclerotinia minor. S. sclerotiorum growth was more suitable when the culture temperature was 15°C-25°C, pH 5.0, carbon source was maltose and nitrogen source was yeast powder. S. minor growth was more suitable when the culture temperature was 15°C, pH 5.0, the carbon source was glucose, and the nitrogen source was yeast powder. The results identified the pathogens as S. sclerotiorum and S. minor. To the best of our knowledge, this is the first report of S. sclerotiorum and S. minor causing sclerotinia rot on Z. candida. We herein aimed to identify the causal agent of sclerotinia rot of Z. candida in China based on morphological characteristics, molecular identification, and pathogenicity tests. Performed the experiments on the biological characteristics, to understand the law of disease occurrence. We also evaluated methods for the effective control of this disease. Our findings provide support for further studies on the pathogenesis mechanism of sclerotinia rot. [ABSTRACT FROM AUTHOR]

Tragopogon coelesyriacus is a pharmacotherapeutic herbaceous plant belonging to the Asteraceae family and consumed as a vegetable. Here, the methanolic and water extracts of T. coelesyriacus were obtained from its aboveground parts (stem, leaves, and flowers), and the phytochemical potentials were investigated by LC‐HRMS (liquid chromatography–high resolution mass spectrometry) analysis for the first time. The antibacterial, antifungal, and anticarcinogenic activities of T. coelesyriacus extracts were investigated using experimental and in silico methods. T. coelesyriacus methanol extract revealed remarkable inhibitory activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumonia (MICs = 0.83, 1.67, and 1.67 mg/mL, respectively) compared to Escherichia coli and Enterobacter aerogenes (MIC = 53.3 mg/mL). Inhibitory effects of T. coelesyriacus methanolic extracts were also observed in all Candida species tested, with the highest inhibition on Candida krusei (MIC = 0.83 mg/mL), whereas no inhibitory effect was identified from the water extract. Additionally, both T. coelesyriacus methanolic (IC50 = 86 μg/mL) and water (IC50 = 92 μg/mL) extracts revealed significant selective anticarcinogenic effects on AR42J pancreatic cancer cells. HeLa and MDA‐MB‐231 cells were, however, more resilient to methanol and water extract, respectively. In silico analyses further elucidated the noteworthy antibacterial potential of keracyanin chloride on S. aureus MurB enzyme and the remarkable inhibitory potential of naringin on FYN kinase specific for pancreatic cancer (AR42J) development. In conclusion, T. coelesyriacus phytochemicals with antibacterial, antifungal, and anticancer properties were revealed for the first time, and molecular docking studies on potential targets confirmed good agreement with experimental findings. Therefore, the current studies on T. coelesyriacus provide the basis for investigating new pharmaceutical potentials of other Tragopogon members. [ABSTRACT FROM AUTHOR]

Introduction: Candida auris is a recently discovered yeast with a multi-drug resistant profile associated with high mortality rates. The rapid identification of Candida auris in hospital settings is crucial to allow appropriate therapeutic and rapid implementation of infection management measures. The aim of this study was to develop a lateral flow immunoassay (LFIA) for the rapid identification of Candida auris. Methods: Highly specific monoclonal antibodies were obtained by immunizing mice with membrane proteins from Candida auris which were then used to develop a LFIA whose performance was assessed by testing 12 strains of Candida auris and 37 strains of other Candida species. Isolates were grown on either Sabouraud dextrose, CHROMagarTM Candida Plus or HardyCHROM™ Candida + auris agar plates. The strains were also cultured on salt sabouraud-dextrose with chloramphenicol or a commercially available Salt-Sabouraud Dulcitol Broth with chloramphenicol and gentamicin, and processed using a simple centrifugation protocol to recover a pellet. Finally, the colonies or yeast extract were transferred to the LFIA to determine the specificity and sensitivity of the assay. Results: The LFIA reached 100% specificity and sensitivity from solid agar plates. For both enrichment broths, some Candida non-auris species were able to grow, but the LFIA remained 100% specific. The use of a dextrose-based sabouraud broth resulted in earlier identification with the LFIA, with most of the Candida auris strains detected at 24 h. Conclusion: The developed LFIA prototype represents a powerful tool to fight the emerging threat of Candida auris. Clinical validation represents the next step. [ABSTRACT FROM AUTHOR]

Background Primary antifungal prophylaxis with mold-active azoles is used to prevent invasive fungal infections in patients with high-risk hematological disorders; however, breakthrough infections occur, and the reasons for treatment failure are still not fully understood. To help inform clinical decisions, we sought to define microbiological, clinical, and pharmacological characteristics of proven and probable breakthrough invasive fungal infections (bIFIs) in patients with high-risk hematological disorders receiving voriconazole or posaconazole prophylaxis. Methods We performed a systematic review of the literature following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search strategy was last conducted on 19 April 2023. Results We assessed 5293 studies for eligibility, and 300 were selected for data extraction. These studies described 1076 cases of bIFIs occurring under voriconazole (42.5%) or posaconazole (57.5%). The most commonly found pathogens were Aspergillus (40%), Mucorales (20%), Candida (18%), and Fusarium (9%) species. Mucorales were more frequent among voriconazole-emerging cases, whereas Aspergillus and Fusarium were more prevalent among posaconazole-emerging cases. Definitive, putative, or probable antifungal resistance was found in 31% of cases. Therapeutic drug monitoring showed subtherapeutic azole concentration in 32 of 90 (36%) cases. Infection-related mortality was reported in 117 cases and reached 35%. Conclusions In our systemic review, the most common bIFIs were aspergillosis, mucormycosis, candidiasis, and fusariosis. Antifungal resistance explains only a minority of cases. Subtherapeutic prophylaxis was frequent but rarely reported. Prospective studies are needed to better understand these infections and to establish optimal management. [ABSTRACT FROM AUTHOR]

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Filamentous cell growth is a vital property of fungal pathogens. The mechanisms of filamentation in the emerging multidrug-resistant fungal pathogen Candida auris are poorly understood. Here, we show that exposure of C. auris to glycerol triggers a rod-like filamentation-competent (RL-FC) phenotype, which forms elongated filamentous cells after a prolonged culture period. Whole-genome sequencing analysis reveals that all RL-FC isolates harbor a mutation in the C2H2 zinc finger transcription factor-encoding gene GFC1 (Gfc1 variants). Deletion of GFC1 leads to an RL-FC phenotype similar to that observed in Gfc1 variants. We further demonstrate that GFC1 mutation causes enhanced fatty acid β-oxidation metabolism and thereby promotes RL-FC/filamentous growth. This regulation is achieved through a Multiple Carbon source Utilizer (Mcu1)-dependent mechanism. Interestingly, both the evolved RL-FC isolates and the gfc1Δ mutant exhibit an enhanced ability to colonize the skin. Our results reveal that glycerol-mediated GFC1 mutations are beneficial during C. auris skin colonization and infection. Author summary: Candida auris is an emerging multidrug-resistant fungal pathogen that has rapidly spread worldwide in the past decade. This fungus can manifest filamentous morphology under certain conditions, such as passage through a mammalian host. Here, we demonstrate that exposure of C. auris to glycerol triggers a rod-like filamentation-competent (RL-FC) phenotype, resulting in elongated filamentous cells post a prolonged cultivation. Whole-genome sequencing analysis indicates that mutation of a C2H2 zinc finger transcription factor-encoding gene GFC1 is responsible for the generation of RL-FC/filamentous phenotype and enhances ability of skin colonization. We further substantiate that Multiple Carbon source Utilizer (Mcu1)-mediated fatty acid β-oxidation metabolism contributes to Gfc1-suppressed filamentous growth. Our findings link a single gene mutation to metabolic adaptation and acquisition of filamentous competence in C. auris, shedding light on how adaptive traits emerge in pathogens to enhance colonization and infection of the host. [ABSTRACT FROM AUTHOR]

Candida auris is an emerging pathogenic yeast that has been categorized as a global public health threat and a critical priority among fungal pathogens. Despite this, the immune response against C. auris infection is still not well understood. Hosts fight Candida infections through the immune system that recognizes pathogen-associated molecular patterns such as β-glucan, mannan, and chitin on the fungal cell wall. In this study, levels of β-glucan and mannan exposures in C. auris grown under different physiologically relevant stimuli were quantified by flow cytometry-based analysis. Lactate, hypoxia, and sublethal concentration of fluconazole trigger a decrease in surface β-glucan while low pH triggers an increase in β-glucan. There is no inverse pattern between exposure levels of β-glucan and mannan in the cell wall architecture among the three clades. To determine the effect of cell wall remodeling on the immune response, a phagocytosis assay was performed, followed by quantification of released cytokines by ELISA. Lactate-induced decrease in β-glucan leads to reduced uptake of C. auris by PMA-differentiated THP-1 and RAW 264.7 macrophages. Furthermore, reduced production of CCL3/MIP-1⍺ but not TNF-⍺ and IL-10 were observed. An in vivo infection analysis using silkworms reveals that a reduction in β-glucan triggers an increase in the virulence of C. auris. This study demonstrates that β-glucan alteration occurs in C. auris and serves as an escape mechanism from immune cells leading to increased virulence. [ABSTRACT FROM AUTHOR]

Fungal infections are incurring high risks in a range from superficial mucosal discomforts (such as oropharyngeal candidiasis and vulvovaginal candidiasis) to disseminated life-threatening diseases (such as invasive pulmonary aspergillosis and cryptococcal meningitis) and becoming a global health problem in especially immunodeficient population. The major obstacle to conquer fungal harassment lies in the presence of increasing resistance to conventional antifungal agents used in newly clinically isolated strains. Although recombinant cytokines and mono-/poly-clonal antibodies are added into antifungal armamentarium, more effective antimycotic drugs are exceedingly demanded. It is comforting that the development of fungal vaccines and adjuvants opens up a window to brighten the prospective way in the diagnosis, prevention and treatment of fungal assaults. In this review, we focus on the progression of several major fungal vaccines devised for the control of Candida spp., Aspergillus spp., Cryptococcus spp., Coccidioides spp., Paracoccidioides spp., Blastomyces spp., Histoplasma spp., Pneumocystis spp. as well as the adjuvants adopted. We then expound the interaction between fungal vaccines/adjuvants and host innate (macrophages, dendritic cells, neutrophils), humoral (IgG, IgM and IgA) and cellular (Th1, Th2, Th17 and Tc17) immune responses which generally experience immune recognition of pattern recognition receptors, activation of immune cells, and clearance of invaded fungi. Furthermore, we anticipate an in-depth understanding of immunomodulatory properties of univalent and multivalent vaccines against diverse opportunistic fungi, providing helpful information in the design of novel fungal vaccines and adjuvants. [ABSTRACT FROM AUTHOR]

Background: Bacterial aggregation has been shown to occur in synovial fluid which are resistant to high concentrations of antibiotics. Yet the propensity of Candida spp. to form aggregates is unknown. Objective: To assess the ability of numerous Candida spp. to form synovial fluid aggregates and the clinical ramifications of the aggregates. Methods: Nine different Candidal prosthetic joint infection clinical isolates were evaluated for their ability to form aggregates at static and dynamic conditions and their resistance to high concentrations of amphotericin. Furthermore, the ability of tissue plasminogen activator (TPA) to disrupt the aggregates and enhance amphotericin activity was assessed. Results: The results show that all species of Candida spp. evaluated formed aggregates in synovial fluid under dynamic conditions that were resistant to amphotericin. Yet no aggregates formed in tryptic soy broth under any conditions or in synovial fluid under static conditions. As well, when TPA was combined with amphotericin there was a statistically significant decrease (p <.005) in the amount of colony forming units per mL for all Candidal species evaluated. Interestingly, for Candida krusei there was no colony forming units observed after exposure to TPA and amphotericin. Conclusion: Our findings suggest that Candidal species form synovial fluid aggregates that are resistant to high dose amphotericin similar to those that occur with bacteria. However, the varying ability of the different Candida spp. to form hyphae and pseudohyphae compared to yeast cells may have direct impacts on the hardiness of the aggregates and thereby have clinical ramifications with respect to treatment durations. [ABSTRACT FROM AUTHOR]

Background: Candida auris, a multidrug‐resistant fungal pathogen, has received considerable attention owing to its recent surge, especially in South America, which coincides with the ongoing global COVID‐19 pandemic. Understanding the clinical and microbiological characteristics of outbreaks is crucial for their effective management and control. Objective: This retrospective observational study aimed to characterize a C. auris outbreak at a Peruvian referral hospital between January 2021 and July 2023. Methods: Data were collected from hospitalized patients with positive C. auris culture results. Microbiological data and antifungal susceptibility test results were analysed. Additionally, infection prevention and control measures have been described. Statistical analysis was used to compare the characteristics between the infected and colonized patients. Results: Thirty‐three patients were identified, mostly male (66.7%), with a median age of 53 years. Among them, 18 (54.5%) were colonized, and 15 (45.5%) were infected. Fungemia was the predominant presentation (80%), with notable cases of fungemia in tuberculosis patients with long‐stay devices for parenteral anti‐tuberculosis therapy. Seventy‐five percent of the isolates exhibited fluconazole resistance. Echinocandins were the primary treatment, preventing fungemia recurrence within 30 days. Infected patients had significantly longer hospital stays than colonized patients (100 vs. 45 days; p =.023). Hospital mortality rates were 46.7% and 25% in the infected and fungemia patients, respectively. Simultaneous outbreaks of multidrug‐resistant bacteria were documented. Conclusions: This study underscores the severity of a C. auris outbreak at a referral hospital in Peru, highlighting its significant impact on patient outcomes and healthcare resources. The high prevalence of fluconazole‐resistant isolates, leading to prolonged hospital stay and high mortality rates, particularly in cases of fungemia, underscores the critical need for effective infection prevention and control strategies. [ABSTRACT FROM AUTHOR]

Background: Candida vulturna is an emerging pathogen belonging to the Metshnikowiaceae family together with Candida auris and Candida haemulonii species complex. Some strains of this species were reported to be resistant to several antifungal agents. Objectives: This study aims to address identification difficulties, evaluate antiungal susceptibilities and explore the molecular mechanisms of azole resistance of Candida vulturna. Methods: We studied five C. vulturna clinical strains isolated in three Colombian cities. Identification was performed by phenotypical, proteomic and molecular methods. Antifungal susceptibility testing was performed following CLSI protocol. Its ERG11 genes were sequenced and a substitution was encountered in azole resistant isolates. To confirm the role of this substitution in the resistance phenotype, Saccharomyces cerevisiae strains with a chimeric ERG11 gene were created. Results: Discrepancies in identification methods are highlighted. Sequencing confirmed the identification as C. vulturna. Antifungal susceptibility varied among strains, with four strains exhibiting reduced susceptibility to azoles and amphotericin B. ERG11 sequencing showed a point mutation (producing a P135S substitution) that was associated with the azole‐resistant phenotype. Conclusions: This study contributes to the understanding of C. vulturna's identification challenges, its susceptibility patterns, and sheds light on its molecular mechanisms of azole resistance. [ABSTRACT FROM AUTHOR]

Background: Candidemia is a diverse condition and associated with a broad spectrum of clinical presentation. As mortality is high, timely diagnosis of candidemia and start of correct therapeutic treatment are essential. Objectives: To investigate characteristics and factors influencing outcomes for patients with candidemia in a Swedish setting. Method: All positive blood cultures for any Candida species in Östergötland County from 2012 to 2016 were screened. Medical records of patients fulfilling all inclusion criteria and no exclusion criteria were retrospectively reviewed to obtain data on risk factors, diagnostic and therapeutic procedures and at what wards candidemia was diagnosed. Univariate logistic regression and multivariable regression analysis were used to obtain odds ratio to determine risk factors for 30‐day all‐cause mortality associated with candidemia. A p‐value <.05 was considered statistically significant. Results: Of all analysed risk factors, increasing age, renal failure with haemodialysis, immunosuppressant treatment, and severity of the infection (i.e. if septic shock was present) were significantly associated with 30‐day mortality in univariate analysis (p <.05). Removal of a central venous catheter or an infectious diseases consultant was associated with a significantly lower odds ratio for death at 30 days (p <.05). With multivariable analysis, age, time to start of treatment and infectious disease consultant remained significant (p <.05). Conclusion: In conclusion, this study provides an update of the epidemiology and outcomes of candidemia in a Swedish setting, highlighting that patients with candidemia are present at various departments and indicates the importance of an infectious disease consultant when candidemia is present. [ABSTRACT FROM AUTHOR]

Although advances in the management of pediatric neoplasms have profoundly improved infectious disease outcomes, invasive fungal diseases (IFDs) remain a major cause of morbidity and mortality in children and adolescents with high-risk hematological malignancies. A retrospective study was conducted in the Pediatric Hematology–Oncology Department of the University General Hospital of Heraklion for 2013–2022 to estimate the prevalence and describe the clinical and epidemiological characteristics of IFDs for pediatric and adolescent patients with neoplasia. Demographic, clinical, and laboratory parameters were analyzed to identify risk factors for the development of IFD. The overall prevalence of IFDs was estimated to be 7.8% (12/154 patients) throughout the study. The mean age at IFD diagnosis was 9.8 years (SD 6.4 years). The most common IFD was possible/probable invasive pulmonary aspergillosis (IPA; in ≈50%), followed by candidemia/invasive candidiasis (in 44%). Candida parapsilosis was the most prevalent Candida species (4/6 events). Of interest, the majority (75%) of IFDs were breakthrough infections. Patients with increased risk for IFDs were those who were colonized by fungi in sites other than the oral cavity, hospitalized in the intensive care unit for >7 days, received >7 different antimicrobials in the last 3 months, or had severe neutropenia for >44 days. Two children out of a total of 12 with IFD died due to refractory disease or relapse (16.7%). More detailed and prospective epidemiological studies on fungal infections in pediatric patients with hematological or solid neoplasms can contribute to the optimization of prevention and treatment. [ABSTRACT FROM AUTHOR]

The occurrence of non-albicans species within the genus Candida poses a major challenge in the clinical setting. Clavispora lusitaniae, formerly known as Candida lusitaniae, has gained attention due to its potential multidrug resistance, particularly to amphotericin B (AmB). While intrinsic resistance to AmB is rare, secondary resistance may develop during treatment due to phenotypic rearrangement and the reorganization of the cell wall. Although there is evidence of genetic variability within C. lusitaniae, comprehensive genomic studies are lacking. This study examines the physiological differences within Candida species and focuses on the medical implications of this. Using two case reports, significant physiological and resistance differences between two strains of C. lusitaniae are demonstrated, highlighting the need for further research into genetic variability. While one strain showed higher resistance to antifungal drugs and slower growth compared to Strain 2, both strains showed minimal beta-D-glucan production, suggesting alternative pathogenic mechanisms. The study underlines the importance of understanding microbial adaptation and selection mechanisms, especially in the clinical setting, to effectively combat emerging drug resistance. Furthermore, research is needed to clarify the complex interplay between environmental causes, physiological traits, and the mechanisms of drug resistance in C. lusitaniae. [ABSTRACT FROM AUTHOR]

In this study, yeasts from the gut of O. barnabita larvae were isolated and molecularly identified. It is worth noting that this research provides the first analysis of the gut yeast community in O. barnabita larvae in Lithuania, which is a significant contribution to the field. Two hermit-like L3-praepupa instars were collected from a decaying oak log in Lithuania. The isolation, morphology, biochemistry, and physiology of the yeast isolates were characterized using standards commonly employed in yeast taxonomy studies. The isolates were identified by sequencing the large subunit (26S) rDNA (D1/D2 domain of the LSU). All gut compartments were colonized by the yeast. A total of 45 yeast strains were obtained from the gut of both O. barnabita larvae, with 23 strains originating from Larva 1, 16 strains from Larva 2, and 6 strains from the galleries. According to our identification results of the 45 yeast strains, most of the species were related to Ascomycota, with most of them belonging to the Saccharomycetales order. Yeasts of the genera Candida, Debaryomyces, Meyerozyma, Priceomyces, Schwanniomyces, Spencermartinsiella, Trichomonascus, and Blastobotrys were present in gut of O. barnabita larvae. Species of the Trichosporonales order represented the Basidiomycota phylum. [ABSTRACT FROM AUTHOR]

The present study was performed to determine if ingesting a blend of probiotics plus amylase would alter the abundance and diversity of gut microbiota in subjects consuming the blend over a 6-week period. 16S and ITS ribosomal RNA (rRNA) sequencing was performed on fecal samples provided by subjects who participated in a clinical study where they consumed either a probiotic amylase blend (Bifidobacterium breve 19bx, Lactobacillus acidophilus 16axg, Lacticaseibacillus rhamnosus 18fx, and Saccharomyces boulardii 16mxg, alpha amylase (500 SKB (Alpha-amylase-Dextrinizing Units)) or a placebo consisting of rice oligodextrin. The abundance and diversity of both bacterial and fungal organisms was assessed at baseline and following 6 weeks of probiotic amylase blend or placebo consumption. In the subjects consuming the probiotic blend, the abundance of Saccharomyces cerevisiae increased 200-fold, and its prevalence increased (~20% to ~60%) (p ≤ 0.05), whereas the potential pathogens Bacillus thuringiensis and Macrococcus caseolyticus decreased more than 150- and 175-fold, respectively, after probiotic-amylase blend consumption. We also evaluated the correlation between change in microbiota and clinical features reported following probiotic amylase consumption. Nine (9) species (seven bacterial and two fungal) were significantly (negatively or positively) associated with the change in 32 clinical features that were originally evaluated in the clinical study. Oral supplementation with the probiotic-amylase blend caused a marked increase in abundance of the beneficial yeast S. cerevisiae and concomitant modulation of gut-dwelling commensal bacterial organisms, providing the proof of concept that a beneficial commensal organism can re-align the gut microbiota. [ABSTRACT FROM AUTHOR]

Copper selenide nanoparticles (Cu2-x Se NPs) have received a lot of attention in recent decades due to their interesting properties and potential applications in various areas such as electronics, health, solar cells, etc. In this study, details of the synthesis and characterization of copper selenide nanoparticles modified with gum arabic (GA) are reported. Also, through transmission electronic microscopy (TEM) analysis, the transformation of the morphology and particle size of copper selenide nanoparticles in aqueous solution was studied. In addition, we present an antimicrobial study with different microorganisms such as Staphylococcus aureus (S. aureus), Escherichia coli (E. coli) and Candida albiacans (C. albicans). Copper selenide nanoparticles were characterized by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), differential scanning calorimetry analysis (DSC) and TEM. XRD confirmed the crystal-line structure of the nanoparticles such as cubic berzelanite with a particle size of 6 nm ± 0.5. FTIR and TGA corroborated the surface modification of copper selenide nanoparticles with gum arabic, and DSC suggested a change in the structural phase from cubic to hexagonal. TEM analysis demonstrated that the surface modification of the Cu2-x Se NPs stabilized the nanostructure of the particles, preventing changes in the morphology and particle size. The antimicrobial susceptibility analysis of copper selenide nanoparticles indicated that they have the ability to inhibit the microbial growth of Staphylococcus aureus, Escherichia coli and Candida albicans. [ABSTRACT FROM AUTHOR]