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Candida tropicalis (C. tropicalis) is a zoonotic pathogen that is widespread in the environment and in recent years an increasing number of dairy cows have been infected with the fungus causing mastitis in cows.In this study, 37 milk samples from the udders of cows with clinical mastitis were collected from a dairy farm in Guangxi Province, China, from which C. tropicalis was isolated and identified, and then the isolated fungi were subjected to genome frame map sequencing, genome functional analysis as well as comparative genome analysis of the sequencing results, and combined with the virulence test of the fungi and drug sensitivity test of the fungi determined in infected mice, the resistance genes and pathogenicity of the fungi were Analysis of resistance genes and pathogenicity.Our study results revealed the isolation and characterisation of C. tropicalis from diseased cows, with a genome length of approximately 14.27 Mb. Functional annotation of the genome identified 4068 genes associated with C. tropicalis. The strain exhibited a chemoresistance mutation in the gene cyp51,a virulence-enhancing mutation in the gene VTC4, and mutations in genes linked to drug resistance. Pathogenicity tests demonstrated that C. tropicalis could induce damage to the internal organs of mice, leading to different levels of cyanosis in the abdominal cavity, white necrotic foci on the surface of internal organs, lung hemorrhage, and enlargement of the spleen and thymus.Histological sections also revealed varying degrees of hemorrhage and degenerative changes in the cells of different organs in the mice. Drug sensitivity tests showed that the fungus was highly sensitive to nystatin and ketoconazole, moderately sensitive to amphotericin B, and insensitive to antibiotics such as itraconazole, gentamicin, and penicillin. In conclusion, C. tropicalis isolated from dairy cows in the Guangxi region in this study was pathogenic and resistant to azoles such as itraconazole and fluconazole, and this study provides a theoretical basis for the further screening of novel resistance genes in C. tropicalis, as well as providing a certain reference for the drugs used for the treatment of fungal cow mastitis in this region., (© 2024. The Author(s).)

Rationale: Studies on Candida infections in the central nervous system, especially in infants and young children that did or did not have postoperative surgery, are rarely reported. Thus far, intrathecal (i.t.) amphotericin B (AmB) is not routinely recommended as a therapy for Candida meningitis. We report the first case of Candida meningitis in an infant who underwent abdominal surgery and was successfully treated with i.t. and intravenous (i.v.) AmB in the mainland of China., Patient Concerns: Candida meningitis was confirmed by culture and immunoserological tests in a 1-day-old girl after surgery. She was treated with fluconazole for 1 month, but the patient's symptoms showed no improvement., Diagnoses: After surgery, the infant started having recurrent attacks of fever, and laboratory tests of the cerebrospinal fluid (CSF) revealed antigens of Candida tropicalis. CSF tests revealed a high total protein level and a low glucose level. She was diagnosed with a secondary Candida meningitis., Interventions: After azole therapy failure, intrathecal and intravenous AmB therapy were used as rescue therapies., Outcomes: After nearly 2 months of AmB treatment, all repeat CSF cultures were negative, the infant was deemed stable and was discharged home, and she continued taking voriconazole orally as an outpatient., Lessons: The combination of i.t. and i.v. administration of AmB can provide a safe and effective alternative to managing this rare but severe disease., Competing Interests: The authors have no conflicts of interests., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Emergence of Candida tropicalis , which causes potential life-threatening invasive candidiasis, is often associated with colonization of medical devices as biofilm. Biofilm plays an important role in the virulence of the pathogen because of its complex structure, which provides resistance to conventional antimicrobials. In this study, the metabolic response of a clinical strain of C. tropicalis colonizing three distinct surfaces (polytetrafluoroethylene (PTFE), polystyrene, and polycarbonate) as well as the expression of virulence and stress related genes ( ALS3, Hsp21 , SAP1 , SAP2 , SAP3 , and CYR1 ), were explored. Our results showed that lesser biofilm was developed on PTFE compared to polystyrene and polycarbonate. GS-MS metabolic analysis identified a total of 36 metabolites in the intracellular extract of cells grown on polystyrene, polycarbonate, and PTFE, essentially belonging to central carbon metabolism, amino acids, and lipids metabolism. The metabolic analysis showed that saturated and unsaturated fatty acids are preferentially produced during biofilm development on polycarbonate, whereas trehalose and vitamin B6, known as cellular protectors against a variety of stressors, were characteristic of biofilm on PTFE. The results of the transcriptomic analysis consider the different degrees of colonization of the three substrates, being CYR1 , which encodes the component of signaling pathway of hyphal formation-cAMP-PKA, downregulated in PTFE biofilm compared to polycarbonate or polystyrene biofilms, while Hsp21 was upregulated in concomitance with the potential unfavorable conditions for biofilm formation on PTFE. Overall, this work provides new insights into the knowledge of C. tropicalis biofilm development on surfaces of medical relevance in the perspective of improving the management of Candida infections.

Background: Vulvovaginal candidiasis (VVC) is a common vaginitis in females. The commonly used diagnostic method, 10% potassium hydroxide (KOH) smear microscopy, makes it not very easy to recognize fungi., Methods: Vaginal secretions were collected from clinically suspected VVC patients and divided into four groups and examined using KOH, CFW (Calcofluor White), FB 85(fluorescent brightener 85), and culture. The data were statistically analyzed., Results: In total, 110 patients with suspected VVC were recruited. The positive rates of KOH, CFW, FB 85, and the culture method were 68.2%, 64.5%, 61.8%, and 77%, respectively. According to the McNemar test, there was no statistically significant difference between the KOH, CFW, and the FB 85 methods (p > 0.05). However, CFW had a shorter diagnosis time than the KOH method and had a statistically significant difference (p < 0.001). Moreover, CFW has the highest sensitivity, specificity, and accuracy. In morphological recognition, it was easier to recognize fungal structures with CFW and FB 85 than with the KOH., Conclusions: The fluorescent method is a good method for the diagnosis of VVC. And the fungi can be found more quickly. Similar to CFW, FB 85 is also a potential good fluorescent reagent for the diagnosis of VVC and has potential value for application in clinical fungal infection diseases., (© 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

NDT80-like family genes are highly conserved across a large group of fungi, but the functions of each Ndt80 protein are diverse and have evolved differently among yeasts and pathogens. The unique NDT80 gene in budding yeast is required for sexual reproduction, whereas three NDT80-like genes, namely, NDT80, REP1, and RON1, found in Candida albicans exhibit distinct functions. Notably, it was suggested that REP1, rather than RON1, is required for N-acetylglucosamine (GlcNAc) catabolism. Although Candida tropicalis, a widely dispersed fungal pathogen in tropical and subtropical areas, is closely related to Candida albicans, its phenotypic, pathogenic and environmental adaptation characteristics are remarkably divergent. In this study, we focused on the Ron1 transcription factor in C. tropicalis. Protein alignment showed that C. tropicalis Ron1 (CtRon1) shares 39.7% identity with C. albicans Ron1 (CaRon1). Compared to the wild-type strain, the C. tropicalis ron1Δ strains exhibited normal growth in different carbon sources and had similar expression levels of several GlcNAc catabolic genes during GlcNAc treatment. In contrast, C. tropicalis REP1 is responsible for GlcNAc catabolism and is involved in GlcNAc catabolic gene expressions, similar to C. albicans Rep1. However, REP1 deletion strains in C. tropicalis promote hyphal development in GlcNAc with low glucose content. Interestingly, CtRON1, but not CaRON1, deletion mutants exhibited significantly impaired hyphal growth and biofilm formation. As expected, CtRON1 was required for full virulence. Together, the results of this study showed divergent functions of CtRon1 compared to CaRon1; CtRon1 plays a key role in yeast-hyphal dimorphism, biofilm formation and virulence., Lay Abstract: In this study, we identified the role of RON1, an NDT80-like gene, in Candida tropicalis. Unlike the gene in Candida albicans, our studies showed that RON1 is a key regulator of hyphal formation, biofilm development and virulence but is dispensable for N-acetylglucosamine catabolism in C. tropicalis., (© The Author(s) 2020. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Candida tropicalis is a human pathogen that primarily infects the immunocompromised. Whereas the genome of one isolate, C. tropicalis MYA-3404, was originally sequenced in 2009, there have been no large-scale, multi-isolate studies of the genetic and phenotypic diversity of this species. Here, we used whole genome sequencing and phenotyping to characterize 77 isolates of C. tropicalis from clinical and environmental sources from a variety of locations. We show that most C. tropicalis isolates are diploids with approximately 2-6 heterozygous variants per kilobase. The genomes are relatively stable, with few aneuploidies. However, we identified one highly homozygous isolate and six isolates of C. tropicalis with much higher heterozygosity levels ranging from 36-49 heterozygous variants per kilobase. Our analyses show that the heterozygous isolates represent two different hybrid lineages, where the hybrids share one parent (A) with most other C. tropicalis isolates, but the second parent (B or C) differs by at least 4% at the genome level. Four of the sequenced isolates descend from an AB hybridization, and two from an AC hybridization. The hybrids are MTLa/α heterozygotes. Hybridization, or mating, between different parents is therefore common in the evolutionary history of C. tropicalis. The new hybrids were predominantly found in environmental niches, including from soil. Hybridization is therefore unlikely to be associated with virulence. In addition, we used genotype-phenotype correlation and CRISPR-Cas9 editing to identify a genome variant that results in the inability of one isolate to utilize certain branched-chain amino acids as a sole nitrogen source., Competing Interests: The authors have declared that no competing interests exist.

Nosocomial Candida colonization causes Systemic candidiasis in human with invasive infections in immunocompromised patients. Of all Candida spp., C. albicans is dominant in morbidity of all systemic candidiasis but C. tropicalis is phenomenal in mortality, virulence aspects and resistance development against antifungal drugs. The present study investigated the synergistic anti-virulent activity of myristic acid (MA) and palmitic acid (PA) against insidious dimorphic Candida spp. (C. albicans and C. tropicalis). In vitro and qPCR results revealed the mechanisms of MA-PA combination effectively inhibiting various virulence aspects such as biofilm, hyphal formation, secreted aspartyl proteases, lipases, ergosterol biosynthesis and drug effluxes. Further, in Danio rerio (Zebrafish), the MA-PA treatment increased the survival of animals and also the treated groups showed decreased level of fungal burden compared to the infected controls, after 3 rd day of post infection. Histopathology of vital organs and SEM analysis of skin revealed a drastic recovery and reduced the inflammation of both Candida spp. infections in MA-PA treated animals. In addition, MA-PA treatment reduced the haemolysin and increased the susceptibility of Candida spp. in human blood model. Hence, this study suggested the therapeutic utilization of MA-PA as synergistic combination for their anti-inflammatory potency against systemic candidiasis and candidemia., (Copyright © 2020. Published by Elsevier Masson SAS.)

Candida tropicalis is an emerging fungal pathogen associated with high mortality. We aimed to compare adherence capability of C. tropicalis to polystyrene and epithelial cell lines (HeLa and Vero), and determine whether adherent blastoconidia is cell-type specific. Blastoconidia adhesion to epithelial cells and polystyrene were determined by crystal violet assay. The percentage of epithelial cells with adhered blastoconidia and the number of adhered blastoconidia per cell line were determined by light microscopy. The correlation between adhesion surfaces was assessed by Pearson's correlation coefficient. The adhesiveness of C. tropicalis to polystyrene was greater than that observed for ephitelial cells. High correlation values (r 2 0.9999222, p 0.007941) were found for the adhesion capability between biotic and polystyrene surface for isolates 100.10 (obtained from blood) and 335.07 (obtained from tracheal secretion). The number of adherent blastoconidia per HeLa cell was greater in comparison to that observed for Vero cells (P<0.05). Further, high correlation (r 2 1, p 0.0001) was found for the adhesion ability between HeLa cells and Vero cells. The results suggest a correlation of C. tropicalis adhesion capability among different surfaces, and that the adhesion to epithelial cells is specific to the cell type., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Updated information on the epidemiology of candidemia, particularly during severe socioeconomic events, is important for proper management of these infections. A systematic literature review on candidemia in Greece and a retrospective surveillance study were conducted in a tertiary university hospital during the years of the recent financial crisis (2009 to 2018) in order to assess changes in incidence rates, patient characteristics, species distribution, antifungal susceptibilities, and drug consumption. The average annual incidence of 429 candidemic episodes was 2.03/10,000 bed days, with 9.88 in adult intensive care units (ICUs), 1.74 in surgical wards, and 1.81 in internal medicine wards, where a significant increase was observed (1.15, 1.85, and 2.23/10,000 bed days in 2009 to 2011, 2012 to 2014, and 2015 to 2018, respectively; P  = 0.004). Candida albicans was the most common species (41%), followed by Candida parapsilosis species complex [SC] (37%), Candida glabrata SC (11%), Candida tropicalis (7%), Candida krusei (1%), and other rare Candida spp. (3%). Mixed infections were found in 20/429 (4.7%) cases, while 33 (7%) cases were due to non- Candida spp. Overall, 44/311 (14%) isolates were resistant/non-wild type (WT) to the nine antifungals tested, with 23/113 (20%) C. parapsilosis SC and 2/34 (6%) C. glabrata SC isolates being resistant to fluconazole (1 panechinocandin and 2 panazole resistant). All isolates were susceptible/WT to amphotericin B and flucytosine. While the overall consumption of antifungals diminished ( P  = 0.02), with a mean of 17.93 defined daily doses (DDD)/100 bed days, increased micafungin use was correlated with the rise in C. parapsilosis SC ( P  = 0.04). A significant increase of candidemia in internal medicine wards and of C. parapsilosis SC infections was found during the years of financial crisis. Although resistance rates remain low (<14%), fluconazole-resistant C. parapsilosis SC and multidrug-resistant C. glabrata SC isolates are of major concern., (Copyright © 2020 American Society for Microbiology.)

Rationale: The emphysematous prostatic abscess is a rare but potentially life-threatening clinical condition. The early diagnosis is difficult due to nonspecific symptoms., Patient Concerns: A 72-year-old man with poorly controlled diabetes mellitus was admitted to hospital because of dysuria and acute urine retention. He had a refractory fever after admission., Diagnoses: The diagnosis of emphysematous prostatic abscess was confirmed by culture of catheterized urine and pelvic CT., Interventions: We tried to give antimicrobial treatment and control of blood glucose at first, but the infection could not be controlled by antibiotic therapy and control of blood glucose. TRUS-guided aspiration was performed, but obviously not adequate for abscess drainage and the abscess progressed. TUR was then performed and the infection was gradually controlled., Outcomes: Pelvic CT scan 1 month after discharge showed complete resolution of the EPA., Lessons: Given the poor conservative treatment effect of emphysematous prostatic abscesses, CT or TRUS should be performed in the patients with suspected diagnosis. Early and appropriate drainage with proper antibiotic therapy is important to achieve a favorable outcome.

We aim to assess intra- and interspecies differences in the virulence of Candida spp. strains causing candidemia using the invertebrate Galleria mellonella model. We studied 739 Candida spp. isolates (C. albicans [n = 373], C. parapsilosis [n = 203], C. glabrata [n = 92], C. tropicalis [n = 53], and C. krusei [n = 18]) collected from patients with candidemia admitted to Gregorio Marañon Hospital (Madrid, Spain). Species-specific infecting inocula (yeast cells/larva) were adjusted (5 × 105 [C. albicans, and C. tropicalis], 2 × 106-5 × 106 [C. parapsilosis, C. glabrata, and C. krusei]) and used to infect 10 larvae per isolate; percentage of survival and median survival per isolate were calculated. According to the interquartile range of the median survival, isolates with a median survival under P25 were classified as of high-virulence and isolates with a median survival over P75 as of low virulence. The median survival of larvae infected with different species was variable: C. albicans (n = 2 days, IQR <1-3 days), C. tropicalis (n = 2 days, IQR 1.5-4 days), C. parapsilosis (n = 2 days, IQR 2-3.5 days), C. glabrata (n = 3 days, IQR 2-3 days), and C. krusei (n = 7 days, 6.5->8 days) (P < .001). Differences in virulence among species were validated by histological examination (day +1 post-infection) in the larvae infected by the isolates of each virulence category and species. Virulence-related gene expression in C. albicans isolates did not reach statistical significance. We report species-specific virulence patterns of Candida spp. and show that isolates within a given species have different degrees of virulence in the animal model., (© The Author(s) 2019. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Candidiasis affects a wide variety of immunocompromised and medically compromised patients. Candida albicans , a major human fungal pathogen, accounts for about 50% of all cases, while the remainder are caused by the less pathogenic non- albicans Candida species (NACS). These species are believed to be less pathogenic, in part, because they do not filament as readily or robustly as C. albicans , although definitive evidence is lacking. To address this question, we used strains for two NACS, Candida tropicalis and Candida parapsilosis , which were genetically engineered to constitutively express the key transcriptional regulator UME6 and drive strong filamentation both in vitro and during infection in vivo Unexpectedly, both strains showed a dramatic reduction in organ fungal burden in response to UME6 expression. Consistent with these findings, we observed that a C. tropicalis hyperfilamentous mutant was significantly reduced and a filamentation-defective mutant was slightly increased for organ fungal burden. Comprehensive immune profiling generally did not reveal any significant changes in the host response to UME6 expression in the NACS that could explain the increased clearance of infection. Interestingly, whole-genome transcriptional profiling indicated that while genes important for filamentation were induced by UME6 expression in C. tropicalis and C. parapsilosis , other genes involved in a variety of processes important for pathogenesis were strongly downregulated. These findings suggest that there are fundamental evolutionary differences in the relationship between morphology and pathogenicity among Candida species and that NACS do not necessarily possess the same virulence properties as C. albicans IMPORTANCE Many immunocompromised individuals, including HIV/AIDS and cancer patients, are susceptible to candidiasis. About half of all cases are caused by the major fungal pathogen Candida albicans , whereas the remainder are due to less pathogenic non- albicans Candida species (NACS). Generation of filamentous cells represents a major virulence property of C. albicans , and the NACS are believed to be less pathogenic, in part, because they do not filament as well as C. albicans does. To address this question, we determined the pathogenicity of two NACS strains that have been genetically engineered to promote filamentation during infection. Surprisingly, these strains showed a dramatic reduction in pathogenicity. The host immune response did not appear to be affected. However, unlike C. albicans , filamentation of the NACS was associated with downregulation of several genes important for pathogenicity processes. Our results suggest that there are fundamental evolutionary differences in the relationship between filamentation and pathogenesis in NACS compared to C. albicans ., (Copyright © 2019 Banerjee et al.)

Candidemia has been considered a persistent public health problem with great impact on hospital costs and high mortality. We aimed to evaluate the epidemiology and prognostic factors of candidemia in a tertiary hospital in Northeast Brazil from January 2011 to December 2016. Demographic and clinical data of patients were retrospectively obtained from medical records and antifungal susceptibility profiling was performed using the broth microdilution method. A total of 68 episodes of candidemia were evaluated. We found an average incidence of 2.23 episodes /1000 admissions and a 30-day mortality rate of 55.9%. The most prevalent species were Candida albicans (35.3%), Candida tropicalis (27.4%), Candida parapsilosis (21.6%) and Candida glabrata (11.8%). Higher mortality rates were observed in cases of candidemia due to C. albicans (61.1%) and C. glabrata (100%), especially when compared to C. parapsilosis (27.3%). Univariate analysis revealed some variables which significantly increased the probability of death: older age (P = 0.022; odds ratio [OR] = 1.041), severe sepsis (P < 0.001; OR = 8.571), septic shock (P = 0.035; OR = 3.792), hypotension (P = 0.003; OR = 9.120), neutrophilia (P = 0.046; OR = 3.080), thrombocytopenia (P = 0.002; OR = 6.800), mechanical ventilation (P = 0.009; OR = 8.167) and greater number of surgeries (P = 0.037; OR = 1.920). Multivariate analysis showed that older age (P = 0.040; OR = 1.055), severe sepsis (P = 0.009; OR = 9.872) and hypotension (P = 0.031; OR = 21.042) were independently associated with worse prognosis. There was no resistance to amphotericin B, micafungin or itraconazole and a low rate of resistance to fluconazole (5.1%). However, 20.5% of the Candida isolates were susceptible dose-dependent (SDD) to fluconazole and 7.7% to itraconazole. In conclusion, our results could assist in the adoption of strategies to stratify patients at higher risk for developing candidemia and worse prognosis, in addition to improve antifungal management., Competing Interests: The authors have declared that no competing interests exist.

Candida tropicalis is a pathogenic yeast with worldwide recognition as the second or third more frequently isolated species in Latin America, for both superficial and systemic infections. Because of its high prevalence, and growing clinical interest, it is essential to understand genetic variability patterns of this important Candida species in the tropics. Besides belonging to the human normal microbiota, C. tropicalis may be found in other warm blood animals and in the environment, including water and sand of beaches. The aims of the present study were to evaluate genotypic and phenotypic variability of 62 isolates of C. tropicalis obtained from the coastal environment in Northeast Brazil using microsatellite and MALDI-TOF/MS comparisons. There was a relatively low correspondence between these typing techniques employed. Therefore, further studies are needed to consolidate the use of MALDI-TOF/MS as a yeast typing tool. Nevertheless, the two methods employed demonstrated the heterogeneity of C. tropicalis in a coastal environment. We also found relative maintenance of the population structure within the same season, which may reinforce the idea that this species presents the potential to remain in the environment for a long period of time. In addition, highly related strains were found within different geographic points of collection, demonstrating that this strain may be dispersed at long distances, probably influenced by anthropogenic actions and driven by the sea tides and wind., (Copyright © 2018. Published by Elsevier Ltd.)

Background: Adhesion, biofilm formation, yeast-hyphal transition, secretion of enzymes, and hemolytic activity are all considered important factors in Candida tropicalis infection. However, DNA sequence data for this pathogen are limited. In this study, the polymorphism and heterogeneity of genes agglutinin-like sequences (ALS)2, Lipase (LIP)1, LIP4, and secretory aspartyl proteinase tropicalis (SAPT)1-4 as well as the relationship between phenotype and genotype were analyzed., Methods: This study started in August 2013, and ended in July 2017. The complete length of ALS2, LIP1, LIP4, and SAPT1-4 of 68 clinical C. tropicalis isolates was sequenced. Single nucleotide polymorphisms (SNPs) as well as insertions and deletions (indels) were identified within these genes. In addition, phenotypic characteristics of the virulent factors, including adhesion and the secretion of aspartyl proteinases and phospholipases, were determined., Results: There were 73, 24, 17, 16, 13, and 180 SNPs in the genes LIP1, LIP4, SAPT1, SAPT2, SAPT3, and SAPT4, respectively. Furthermore, 209 SNPs were identified in total for the gene ALS2. Interestingly, large fragment deletions and insertions were also found in ALS2. Isolate FXCT 01 obtained from blood had deletions on all 4 sites and showed the lowest adhesion ability on the polymethylpentene surface. In addition, isolates with deletions in the regions 1697 to 1925 and 2073 to 2272 bp displayed relatively low abilities for adhesion and biofilm formation, and this phenotype correlated with the deletions found in ALS2. LIP1, SAPT4, and ALS2 displayed great heterogeneity among the isolates. Large deletions found in gene ALS2 appeared to be associated with the low ability of adhesion and biofilm formation of C. tropicalis., Conclusion: This study might be useful for deeper explorations of gene function and studying the virulent mechanisms of C. tropicalis.

Candida tropicalis isolates often display reduced but persistent growth (trailing) over a broad fluconazole concentration range during EUCAST susceptibility testing. Whereas weak trailing (<25% of the positive growth control) is common and found not to impair fluconazole efficacy, we investigated if more pronounced trailing impacted treatment efficacy. Fluconazole efficacy against two weakly (≤25% growth), two moderately (26% to 50% growth), and one heavily (>70% growth) trailing resistant isolate and one resistant (100% growth) isolate were investigated in vitro and in vivo (in a Galleria mellonella survival model and two nonlethal murine models). CDR1 expression levels and ERG11 sequences were characterized. The survival in fluconazole-treated G. mellonella was inversely correlated with the degree of trailing (71% to 9% survival in treatment groups). In mice, resistant and heavily trailing isolates responded poorly to fluconazole treatment. CDR1 expression was significantly higher in trailing and resistant isolates than in wild-type isolates (1.4-fold to 10-fold higher). All isolates exhibited ERG11 wild-type alleles. Heavily trailing isolates were less responsive to fluconazole in all in vivo models, indicating an impact on fluconazole efficacy. CDR1 upregulation may have contributed to the observed differences. Moderately trailing isolates responded less well to fluconazole in larvae only. This confirms clinical data suggesting fluconazole is effective against infections with such isolates in less severely ill patients and supports the current 50% growth endpoint for susceptibility testing. However, it is still unclear if the gradual loss of efficacy observed for moderately trailing isolates in the larva model may be a reason for concern in selected vulnerable patient populations., (Copyright © 2018 American Society for Microbiology.)

The human fungal pathogen Candida albicans is the major etiological agent of vulvovaginal candidiasis (VVC). Despite this fact, other non- albicans Candida (NAC) species have frequently been reported, as well. Despite their presence in the vaginal environment, little is known about their capacities to elicit immune responses classically associated with C. albicans -mediated immunopathology, including neutrophil recruitment and proinflammatory cytokine signaling. Therefore, using a combination of in vitro and in vivo approaches, we undertook a comparative analysis to determine whether a representative panel of NAC species could colonize, induce immunopathological markers, or cause damage at the vaginal mucosa. Using a murine model of VVC, C. albicans was found to induce robust immunopathology (neutrophils and interleukin 1β [IL-1β]) and elicit mucosal damage. However, all the NAC species tested (including C. dubliniensis , C. tropicalis , C. parapsilosis , C. krusei , C. glabrata , and C. auris ) induced significantly less damage and neutrophil recruitment than C. albicans , despite achieving similar early colonization levels. These results largely correlated with a notable lack of ability by the NAC species (including C. dubliniensis and C. tropicalis ) to form hyphae both in vitro and in vivo Furthermore, both C. dubliniensis and C. tropicalis induced significantly less expression of the ECE1 gene encoding candidalysin, a key fungal virulence determinant driving VVC immunopathology. In order to determine the relative capacities of these species to elicit inflammasome-dependent IL-1β release, both wild-type and NLRP3 -/- THP-1 cells were challenged in vitro While most species tested elicited only modest amounts of IL-1β, challenge with C. albicans led to significantly elevated levels that were largely NLRP3 dependent. Collectively, our findings demonstrate that although NAC species are increasingly reported as causative agents of VVC, C. albicans appears to be exceedingly vaginopathogenic, exhibiting robust immunopathology, hypha formation, and candidalysin expression. Thus, this study provides mechanistic insight into why C. albicans is overwhelmingly the major pathogen reported during VVC., (Copyright © 2018 American Society for Microbiology.)

Candida tropicalis is an opportunistic fungal pathogen responsible for mucosal and systemic infections. The cell wall is the initial contact point between a fungal cell and the host immune system, and mannoproteins are important components that play key roles when interacting with host cells. In Candida albicans, mannans are modified by mannosyl-phosphate moieties, named phosphomannans, which can work as molecular scaffolds to synthesize β1,2-mannooligosaccharides, and MNN4 is a positive regulator of the phosphomannosylation pathway. Here, we showed that C. tropicalis also displays phosphomannans on the cell surface, but the amount of this cell wall component varies depending on the fungal strain. We also identified a functional ortholog of CaMNN4 in C. tropicalis. Disruption of this gene caused depletion of phosphomannan content. The C. tropicalis mnn4Δ did not show defects in the ability to stimulate cytokine production by human mononuclear cells but displayed virulence attenuation in an insect model of candidiasis. When the mnn4Δ-macrophage interaction was analyzed, results showed that presence of cell wall phosphomannan was critical for C. tropicalis phagocytosis. Finally, our results strongly suggest a differential role for phosphomannans during phagocytosis of C. albicans and C. tropicalis.

Fungal infection in severely burned patients is a serious problem due to various factors, such as the extensive application of antibiotics. In this study, we report on the course of severely burned patients with Candida tropicalis burn wound sepsis. Five such cases were reviewed. The patients were treated with itraconazole intravenously and simultaneous antibiotics to prevent bacterial infections. In addition, dermabrasion was used to excise the eschar and the wound surface was covered immediately with dermatoplasty. Meanwhile, the skin necrosis related to the fungal infection was removed. The wound surfaces of all five patients were healed well and the parameters of laboratory examination went back to normal. We assume that prompt diagnosis and timely treatment including extensive debridement of necrosis, antifungal drugs, and antibiotics were the key points leading to favourable outcome., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

To evaluate the pathophysiology of catheter-associated candiduria, the bladders of female mice were infected with Candida tropicalis. One group was implanted with a catheter fragment with preformed biofilm by cystotomy technique, while another group received, in separate, a sterile catheter fragment and a correspondent yeast suspension. The bladder tissues were examined by histopathology and the quantity of colony forming units was evaluated. All the animals presented inflammation and the presence of C. tropicalis was observed in the tissue within 72 h of the introduction of biofilm, while 75% of the mice remained infected after 144 h. However, only 50% of animals from the group infected with C. tropicalis in suspension (planktonic yeasts), exhibited such signs of infection over time. The cystotomy technique is therefore viable in mice, and is an effective model for evaluating the pathogenesis of candiduria from catheter biofilms. The model revealed the potential of C. tropicalis infectivity and demonstrated more effective evasion of the host response in biofilm form than the planktonic yeast., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The increased incidence of severe disseminated infections caused by the opportunistic yeast-like fungi Candida spp. highlights the urgent need for research into the major virulence factors of these pathogens-extracellular aspartic proteinases of the candidapepsin and yapsin families. Classically, these enzymes were considered to be generally destructive factors that damage host tissues and provide nutrients for pathogen propagation. However, in recent decades, novel and more specific functions have been suggested for extracellular candidal proteinases. These include contributions to cell wall maintenance and remodeling, the formation of polymicrobial biofilms, adhesion to external protective barriers of the host, the deregulation of host proteolytic cascades (such as the complement system, blood coagulation and the kallikrein-kinin system), a dysregulated host proteinase-inhibitor balance, the inactivation of host antimicrobial peptides, evasion of immune responses and the induction of inflammatory mediator release from host cells. Only a few of these activities recognized in Candida albicans candidapepsins have been also confirmed in other Candida species, and characterization of Candida glabrata yapsins remains limited., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Metagenomics uses nucleic acid sequencing to characterize species diversity in different niches such as environmental biomes or the human microbiome. Most studies have used 16S rRNA amplicon sequencing to identify bacteria. However, the decreasing cost of sequencing has resulted in a gradual shift away from amplicon analyses and towards shotgun metagenomic sequencing. Shotgun metagenomic data can be used to identify a wide range of species, but have rarely been applied to fungal identification. Here, we develop a sequence classification pipeline, FindFungi, and use it to identify fungal sequences in public metagenome datasets. We focus primarily on animal metagenomes, especially those from pig and mouse microbiomes. We identified fungi in 39 of 70 datasets comprising 71 fungal species. At least 11 pathogenic species with zoonotic potential were identified, including Candida tropicalis. We identified Pseudogymnoascus species from 13 Antarctic soil samples initially analyzed for the presence of bacteria capable of degrading diesel oil. We also show that Candida tropicalis and Candida loboi are likely the same species. In addition, we identify several examples where contaminating DNA was erroneously included in fungal genome assemblies.

Candida tropicalis is one of the most important human fungal pathogens causing superficial infections in locations such as the oral mucosa and genital tract, as well as systemic infections with high mortality. In its sister species Candida albicans, the cyclic AMP/protein kinase A (cAMP/PKA) pathway regulates fungal adhesion and dimorphism, both of which correlate closely with virulence. CaTpk1 and CaTpk2, the catalytic subunits of PKA, not only share redundant functions in hyphal growth, adhesion, and biofilm formation, but also have distinct roles in stress responses and pathogenesis, respectively. However, studies on PKA in the emerging fungal pathogen C. tropicalis are limited. Our results suggest that Tpk1 is involved in cell wall integrity and drug tolerance. The tpk2/tpk2 mutants, which have no protein kinase A activity, have reduced hyphal growth and adhesion. In addition, the tpk1/tpk1 tpk2/tpk2 double deletion mutant demonstrated delayed growth and impaired hyphal formation. In a murine model of systemic infection, both TPK1 and TPK2 were required for full virulence. We further found that EFG1 and HWP1 expression is regulated by PKA, while BCR1, FLO8, GAL4, and RIM101 are upregulated in the tpk1/tpk1 tpk2/tpk2 mutant. This study demonstrates that Tpk1 is involved in drug tolerance and cell wall integrity, while Tpk2 serves as a key regulator in dimorphism and adhesion. Both Tpk1 and Tpk2 are required for growth and full virulence in C. tropicalis.

Background: Studies have shown that radiation from radiotherapy increases the yeast colonization of patients. However it is not clear, if such radiation alters the yeast itself. The aim of the present study was therefore to report the direct impact of gamma radiation on Candida tropicalis., Methods: C. tropicalis was obtained from a patient with a carcinoma, a suspension of this yeast containing 2.0 × 10 3 colony forming units per milliliter was prepared. It was submitted to gamma radiation dosage similar to that used in the treatment of head and neck cancer. After a cumulative dose of 7200 cGy some virulence attributes of C. tropicalis, including macro and micromorphological characteristics, adhesion and biofilm abilities, murine experimental infection and phagocytosis resistance were evaluated on irradiated and non-irradiated yeasts., Results: After irradiation the colony morphology of the yeast was altered from a ring format to a smooth appearance in most colonies. Scanning electron microscopy revealed notable differences in the structures of both these colonies and the yeast cells, with the loss of pseudohyphae following irradiation and an increase in extracellular matrix production. The adherence and biofilm production of the yeast was greater following irradiation, both in terms of the number of yeasts and total biomass production on several abiotic surfaces and TR146 cells. The phagocytic index of the irradiated yeasts was not statistically different; however, the presence of cellular debris was detected in the kidneys of infected animals. Mice infected with irradiated yeasts developed an infection at the site of the yeast inoculation, although systemic infection was unchanged., Conclusions: Our findings show for the first time that C. tropicalis, one of the most important yeasts from colonization, which cause fatal candidemia in cancer patients, is affected by gamma irradiation, with changes to its virulence profile.

Aim: To evaluate if radiation used in radiotherapy can cause changes in the virulence potential of Candida tropicalis ATCC 750., Materials & Methods: C. tropicalis was exposed in vitro to identical dose and scheme of irradiation would be used in patients with head and neck cancer. Some virulence parameters were analyzed before and after irradiation., Results: Colony morphologies were irreversibly affected by irradiation. Increase in growth rate, filamentation, adhesion on cell lines and phagocytosis process were also observed. Overall the irradiated C. tropicalis cells became more efficient at causing systemic infection in mice., Conclusion: γ-radiation induced important changes in C. tropicalis increasing its virulence profile, which could directly affect the relationship between yeasts and hosts.

Objective: Candida species are part of the commensal microflora in many anatomical sites of the human body; however, breach in the integrity of the body part and impaired immunity of the host can lead to invasive candidiasis. A number of virulence determinants could contribute towards its pathogenicity. Thus we attempted to evaluate the in vitro expression of different virulence factors among clinical isolates of Candida species and assayed their susceptibility patterns against a range of antifungal agents., Result: Of the total of 71 isolates we obtained, 48 (67.6%) were Candida albicans, 11 (15.49%) Candida tropicalis, 09 (12.67%) Candida glabrata and 03 (4.22%) were Candida krusei. Proteinase, phospholipase and esterase production could be revealed amongst 43 (60.56%), 44 (61.97%) and 49 (69.01%) isolates respectively. None of the isolates showed DNAase activity. Fifty-five (77.39%) isolates were biofilm producers, and 53 (74.6%) exhibited high cell surface hydrophobicity.

Aim: To investigate the species distribution and antifungal susceptibility profiles of yeast isolates causing invasive infections across Beijing., Materials & Methods: A total of 1201 yeast isolates recovered from blood and other sterile body fluids were correctly identified by matrix-assisted laser desorption/ionization TOF MS supplemented by DNA sequencing. Antifungal susceptibility testing was performed according to the Clinical and Laboratory Standards Institute broth microdilution method., Results: Candida (95.5%) remained the most common yeast species isolated; Candida albicans (38.8%) and Candida parapsilosis (22.6%) were the leading species of candidemia. Azole resistances were mainly observed in Candida glabrata and Candida tropicalis isolates., Conclusion: This study outlined the epidemiologic data of invasive yeast infections and highlighted the need for continuous monitoring of azole resistances among C. glabrata and C. tropicalis isolates in Beijing.

Objective: We investigated the diversity and drug susceptibility of pathogenic yeasts on fruit surfaces., Method: Fruits were purchased from supermarkets and washed with buffer. The pellets were re-suspended in medium after centrifugation. The cell suspensions were plated onto CHROMagar Candida medium. Yeasts were identified by ribosomal DNA sequencing and their drug susceptibilities were determined by broth microdilution assay., Results: Of 184 isolates, comprised of 55 species, from 22 different types of fruits, 29 species, including Candida famata, Candida fermentati, Candida guilliermondii, Candida intermedia, Candida krusei, Candida orthopsilosis, Candida parapsilosis, Candida pelliculosa, Candida tropicalis, and others have been reported to cause diseases in humans. In addition to C. krusei, intrinsically resistant to fluconazole, all Rhodotorula and Rhodosporidium species were resistant to fluconazole. One each of C. tropicalis isolate was belonged to diploid sequence type (DST)149 and DST225, genotypes also detected in isolates from humans. Furthermore, the DST225 isolate was less susceptible to azole drugs. The susceptibilities to azole drugs for clinical and agricultural usage were associated to each other., Conclusion: It is important to be aware of the existence of pathogenic yeasts, especially drug-resistant ones, on the fruit surfaces, a potential route for pathogenic yeasts to be transmitted to humans., (Copyright © 2017. Published by Elsevier Ltd.)

In this study, we present a rare case of fatal breakthrough Candida tropicalis infection in a patient with acute lymphoblastic leukemia (ALL) while on posaconazole prophylaxis. Then, we explore the mechanisms underlying azole resistance by focusing on enhanced efflux pumps and changes in the azole target enzyme Erg11p, which was encoded by the ERG11 gene. Our study demonstrates that Y132C substitution of Erg11p combined with MDR1 overexpression may be the pan-azole resistance mechanisms in Candida tropicalis ., (Copyright © 2017 You et al.)

In some pathogens, trehalose biosynthesis is induced in response to stress as a protection mechanism. This pathway is an attractive target for antimicrobials as neither the enzymes, Tps1, and Tps2, nor is trehalose present in humans. Accumulation of T6P in Candida albicans, achieved by deletion of TPS2, resulted in strong reduction of fungal virulence. In this work, the effect of T6P on Tps1 activity was evaluated. Saccharomyces cerevisiae, C. albicans, and Candida tropicalis were used as experimental models. As expected, a heat stress induced both trehalose accumulation and increased Tps1 activity. However, the addition of 125 μM T6P to extracts obtained from stressed cells totally abolished or reduced in 50 and 60 % the induction of Tps1 activity in S. cerevisiae, C. tropicalis, and C. albicans, respectively. According to our results, T6P is an uncompetitive inhibitor of S. cerevisiae Tps1. This kind of inhibitor is able to decrease the rate of reaction to zero at increased concentrations. Based on the similarities found in sequence and function between Tps1 of S. cerevisiae and some pathogens and on the inhibitory effect of T6P on Tps1 activity observed in vitro, novel drugs can be developed for the treatment of infectious diseases caused by organisms whose infectivity and survival on the host depend on trehalose.

Recently, the proportion of Candida tropicalis in clinical isolates has significantly increased. Some C. tropicalis strains colonize the skin or mucosal surfaces as commensals; others trigger invasive infection. To date, the pathogenicity of C. tropicalis has not been thoroughly researched. This study reports several virulence factors, including biofilm and hyphae formation, proteinase, phospholipase, lipase and hemolytic activity, in 52 clinical isolates of C. tropicalis collected from five hospitals in four provinces of China. Some C. tropicalis tended to produce more hyphae than others in the same circumstance. Six C. tropicalis strains with different morphologies were injected into mice via the tail vein, and the survival proportions and fungal burdens of the strains were evaluated. Hyphal production by C. tropicalis was associated with stronger virulence. RNA sequencing revealed that C. tropicalis with more hyphae up-regulated several genes involved in morphological differentiation and oxidative response, including IF2, Atx1, and Sod2. It appears that hyphal formation plays a vital role in the pathogenicity of C. tropicalis, and interacts with the oxidative stress response to strengthen the organism's virulence., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

Objective: The main goal of this study was to investigate the role of pH on Candida tropicalis virulence determinants, namely the ability to form biofilms and to colonize/invade reconstituted human vaginal epithelia., Methods: Biofilm formation was evaluated by enumeration of cultivable cells, total biomass quantification and structural analysis by scanning electron microscopy and confocal laser scanning microscopy. Candida tropicalis human vaginal epithelium colonization and invasiveness were examined qualitatively by epifluorescence microscopy and quantitatively by a novel quantitative real-time PCR protocol for Candida quantification in tissues., Results: The results revealed that environmental pH influences C. tropicalis biofilm formation as well as the colonization and potential to invade human epithelium with intensification at neutral and alkaline conditions compared to acidic conditions., Conclusions: For the first time, we have demonstrated that C. tropicalis biofilm formation and invasion is highly influenced by environmental pH., (© Crown copyright 2016.)

In the Asia-Pacific region, Candida albicans is the predominant Candida species causing invasive candidiasis/candidemia in Australia, Japan, Korea, Hong Kong, Malaysia, Singapore and Thailand whereas C. tropicalis is the most frequently encountered Candida species in Pakistan and India. Invasive isolates of C. albicans, C. parapsilosis complex and C. tropicalis remain highly susceptible to fluconazole (>90% susceptible). Fluconazole resistance (6.8-15%), isolates with the non-wild-type phenotype for itraconazole susceptibility (3.9-10%) and voriconazole (5-17.8%), and echinocandin resistance (2.1-2.2% in anidulafungin and 2.2% in micafungin) among invasive C. glabrata complex isolates are increasing in prevalence. Moreover, not all isolates of C. tropicalis have been shown to be susceptible to fluconazole (nonsusceptible rate, 5.7-11.6% in China) or voriconazole (nonsusceptible rate, 5.7-9.6% in China).

Phenotypic plasticity, the ability to switch between different morphological types, plays critical roles in environmental adaptation, leading to infections, and allowing for sexual reproduction in pathogenic Candida species. Candida tropicalis, which is both an emerging human fungal pathogen and an environmental fungus, can switch between two heritable cell types termed white and opaque. In this study, we report the discovery of a novel phenotype in C. tropicalis, named the gray phenotype. Similar to Candida albicans and Candida dubliniensis, white, gray, and opaque cell types of C. tropicalis also form a tristable switching system, where gray cells are relatively small and elongated. In C. tropicalis, gray cells exhibit intermediate levels of mating competency and virulence in a mouse systemic infection model compared to the white and opaque cell types, express a set of cell type-enriched genes, and exhibit both common and species-specific biological features. The key regulators of white-opaque transitions, Wor1 and Efg1, are not required for the gray phenotype. A comparative study of the gray phenotypes in C. tropicalis, C. albicans, and C. dubliniensis provides clues to explain the virulence properties and niche preferences of C. tropicalis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

A high intracellular concentration of potassium (200-300 mmol/L) is essential for many yeast cell functions, such as the regulation of cell volume and pH, maintenance of membrane potential, and enzyme activation. Thus, cells use high-affinity specific transporters and expend a lot of energy to acquire the necessary amount of potassium from their environment. In Candida genomes, genes encoding 3 types of putative potassium uptake systems were identified: Trk uniporters, Hak symporters, and Acu ATPases. Tests of the tolerance and sensitivity of C. albicans, C. dubliniensis, C. glabrata, C. krusei, C. parapsilosis, and C. tropicalis to various concentrations of potassium showed significant differences among the species, and these differences were partly dependent on external pH. The species most tolerant to potassium-limiting conditions were C. albicans and C. krusei, while C. parapsilosis tolerated the highest KCl concentrations. Also, the morphology of cells changed with the amount of potassium available, with C. krusei and C. tropicalis being the most influenced. Taken together, our results confirm potassium uptake and accumulation as important factors for Candida cell growth and suggest that the sole (and thus probably indispensable) Trk1 potassium uptake system in C. krusei and C. glabrata may serve as a target for the development of new antifungal drugs.

According to epidemiological data, Candida tropicalis has been related to urinary tract infections and haematological malignancy. Several virulence factors seem to be responsible for C. tropicalis infections, for example: their ability to adhere and to form biofilms onto different indwelling medical devices; their capacity to adhere, invade and damage host human tissues due to enzymes production such as proteinases. The main aim of this work was to study the behaviour of C. tropicalis biofilms of different ages (24-120 h) formed in artificial urine (AU) and their ability to express aspartyl proteinase (SAPT) genes. The reference strain C. tropicalis ATCC 750 and two C. tropicalis isolates from urine were used. Biofilms were evaluated in terms of culturable cells by colony-forming units enumeration; total biofilm biomass was evaluated using the crystal violet staining method; metabolic activity was evaluated by XTT assay; and SAPT gene expression was determined by real-time PCR. All strains of C. tropicalis were able to form biofilms in AU, although with differences between strains. Candida tropicalis biofilms showed a decrease in terms of the number of culturable cells from 48 to 72 h. Generally, SAPT3 was highly expressed. C. tropicalis strains assayed were able to form biofilms in the presence of AU although in a strain- and time-dependent way, and SAPT genes are expressed during C. tropicalis biofilm formation.

The yeast-filament transition is essential for the virulence of a variety of fungi that are pathogenic to humans. N-acetylglucosamine (GlcNAc) is a potent inducer of filamentation in Candida albicans and thermally dimorphic fungi such as Histoplasma capsulatum and Blastomyces dermatitidis. However, GlcNAc suppresses rather than promotes filamentation in Candida tropicalis, a fungal species that is closely related to C. albicans. Despite the intensive study in C. albicans, the regulatory mechanism of filamentation is poorly understood. In this study, we demonstrate that the cAMP signaling pathway plays a central role in the regulation of filamentation in C. tropicalis. By screening an overexpression library of 156 transcription factors, we have identified approximately 40 regulators of filamentous growth. Although most of the regulators (e.g., Tec1, Gat2, Nrg1, Sfl1, Sfl2 and Ash1) demonstrate a conserved role in the regulation of filamentation, similar to their homologues in C. albicans or Saccharomyces cerevisiae, a number of transcription factors (e.g., Wor1, Bcr1, Stp4, Efh1, Csr1 and Zcf17) play a specific role in C. tropicalis. Our findings indicate that multiple interconnected signaling pathways are involved in the regulation of filamentation in C. tropicalis. These mechanisms have conserved and divergent features among different Candida species., (© 2015 John Wiley & Sons Ltd.)

Objective: To determine the in vitro production of virulence factors for Candida (C.) tropicalis, including aspartyl proteinases, phospholipases and hemolytic activities, describe the regulation of virulence factors varying with time in C. tropicalis, and analyze the differences in aspartyl proteinases and hemolytic activities of C. tropicalis isolated from anatomically distinct sites., Methods: A total of 64 C. tropicalis strains were spot-inoculated onto bovine albumin agar, egg yolk agar and sheep blood agar plates, respectively. Then the plates were incubated for 24, 48 and 72 hour at 37 °C, respectively. The aspartyl proteinases, phospholipase and hemolytic activities were determined at each time point, respectively., Results: All the C. tropiclais isolates showed positive aspartyl proteinases and hemolytic activities at each time point, but no phospholipases activity was detected in C. tropicalis. On comparison of aspartyl proteinases and hemolytic activities at different time points, aspartyl proteinases activity at 48 and 72 hour was higher than that at 24 hour. During 72 hour, hemolytic activity of C. tropicalis increased. No statistical significant differences in aspartyl proteinases and hemolytic activities of C. tropicalis were observed among different infection sites (P=0.368 and 0.985)., Conclusion: The C. tropicalis clinical isolates in China have aspartyl proteinases activity, hemolytic activity, but have no phospholipase activity.

Defining the epidemiology of and risk factors for candidaemia is necessary to guide empirical treatment. The objectives of this study were to determine the ranking of Candida among positive blood cultures, to define the epidemiology of candidaemia and to investigate patient characteristics and their relationship with C. albicans vs. non-albicans Candida (NAC) candidaemia. Candidaemia episodes between January 2001 and December 2010 were evaluated retrospectively. Patient characteristics were compared across Candida species. Candida ranked as the fifth most frequently isolated pathogen. Among 381 candidaemia episodes, 58.3% were due to C. albicans, followed by C. parapsilosis (15.2%), C. tropicalis (13.4%) and C. glabrata (6.8%). No statistically significant difference was observed in the distribution of C. albicans vs. NAC (P = 0.432). Patients with NAC had significantly higher rates of haematological disorders (P < 0.001) and neutropenia (P = 0.003), and were older (P = 0.024) than patients with C. albicans, whereas patients with urinary catheters had higher rates of C. albicans (P = 0.007). On species basis, C. tropicalis was more frequently isolated from patients with haematological disorders (P < 0.001) and neutropenia (P = 0.008). Patients with urinary catheters were less likely to have C. parapsilosis (P = 0.043). C. glabrata was most prevalent among patients with solid organ tumours (P = 0.038), but not evident in patients with haematological disorders. Local epidemiological features and risk factors may have important implications for the management of candidaemia., (© 2015 Blackwell Verlag GmbH.)

In vitro studies to fourteen previously synthesized chromone-tetrazoles and four novel fluorine-containing analogs were conducted against pathogenic protozoan (Entamoeba histolytica), pathogenic bacteria (Pseudomonas aeruginosa, and Staphylococcus aureus), and human fungal pathogens (Sporothrix schenckii, Candida albicans, and Candida tropicalis), which have become in a serious health problem, mainly in tropical countries.

Despite therapeutic advances candidiasis remains a common fungal infection most frequently caused by C. albicans and may occur as vulvovaginal candidiasis or thrush, a mucocutaneous candidiasis. Candidiasis frequently occurs in newborns, in immune-deficient people like AIDS patients, and in people being treated with broad spectrum antibiotics. It is mainly due to C. albicans while other species such as C. tropicalis, C. glabrata, C. parapsilosis and C. krusei are increasingly isolated. OTC antifungal dosage forms such as creams and gels can be used for effective treatment of local candidiasis. Whereas, for preventing spread of the disease to deeper vital organs, candidiasis antifungal chemotherapy is preferred. Use of probiotics and development of novel vaccines is an advanced approach for the prevention of candidiasis. Present review summarizes the diagnosis, current status and challenges in the treatment and prevention of candidiasis with prime focus on host defense against candidiasis, advancements in diagnosis, probiotics role and recent progress in the development of vaccines against candidiasis.

Candida tropicalis, a species closely related to Candida albicans, is an emerging fungal pathogen associated with high mortality rates of 40 to 70%. Like C. albicans and Candida dubliniensis, C. tropicalis is able to form germ tubes, pseudohyphae, and hyphae, but the genes involved in hyphal growth machinery and virulence remain unclear in C. tropicalis. Recently, echinocandin- and azole-resistant C. tropicalis isolates have frequently been isolated from various patients around the world, making treatment difficult. However, studies of the C. tropicalis genes involved in drug tolerance are limited. Here, we investigated the roles of calcineurin and its potential target, Crz1, for core stress responses and pathogenesis in C. tropicalis. We demonstrate that calcineurin and Crz1 are required for hyphal growth, micafungin tolerance, and virulence in a murine systemic infection model, while calcineurin but not Crz1 is essential for tolerance of azoles, caspofungin, anidulafungin, and cell wall-perturbing agents, suggesting that calcineurin has both Crz1-dependent and -independent functions in C. tropicalis. In addition, we found that calcineurin and Crz1 have opposite roles in controlling calcium tolerance. Calcineurin serves as a negative regulator, while Crz1 plays a positive role for calcium tolerance in C. tropicalis., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

The objective of the present was to evaluate the influence of local anesthetics protargol, miramistin, chlorohexidine, and photodynamic therapy (PDT) on the polyresistant strain of Candida tropicalis isolated from a sick child presenting with fungal adenoiditis. In vitro experiments were designed to estimate the inactivation potential of the Candida tropicalis blastospore suspension (5.10⁷ CFU/ml) following the preliminary incubation with a 5 mcmol/l methylene blue solution. A Kreolka FDT apparatus operated at the 680 nm wavelength was employed as the source of radiation in a broad power and time ranges. Simultaneously, experiments were carried out to determine the minimum concentration of the protargol, miramistin, and chlorohexidine solutions inhibiting the growth of the same fungal strain. The minimum growth inhibitory concentrations of these solutions were found to be 0.1%, 0.005%, and 0.005% respectively. The photodynamic therapy using the minimal inhibitory dose of 150 J with a 5 min exposition and an output power of 0.5 W completely suppressed the growth of the Candida tropicalis colonies in the presence of methylene blue as the photosensitizer.

Although Candida tropicalis has become an increasingly important human pathogen, little is known regarding its potential to cause disease. In this study we evaluated the phenotypic switching ability of C. tropicalis and analyzed the effect of switching on biological properties related to virulence factors. We demonstrated that C. tropicalis switched spontaneously, reversibly and at high frequency (10(-1) to 10(-3)) when grown on yeast extract-peptone-D-glucose (YPD) agar medium. Phenotypic switching in five clinical isolates of C. tropicalis resulted in colonies exhibiting the following morphologies: crepe, rough, crater, irregular center, mycelial and diffuse. The majority of the variant colonies were associated with higher percentages of filamentous growth relative to their parental unswitched isolates. Significant differences (P < 0.05) in the production of hemolytic factor were found between most of the switched variants and their respective parental counterparts. Variant colonies exhibiting the crepe (derived from isolates 49.07 and 100.10) and rough phenotype (derived from isolate 49.07) had higher biofilm formation than their parental counterparts exhibiting a smooth dome surface (P < 0.05). Our data revealed that switching was correlated with changes in the in vitro minimum inhibitory concentrations (MICs) of a subset of the switched variants phenotypes to itraconazole. While the MIC to itraconazole was higher for crepe variant compared with its parental isolate 49.07, the rough variant of 100.10 had a lower MIC to this antifungal agent. The presented data support the role of phenotypic switching in promoting changes in phenotypic expression of putative virulence traits and itraconazole susceptibility of clinical isolates of C. tropicalis.

Background: According to data from the China Hospital Invasive Fungal Surveillance Net (CHIF-NET) 2010, Candida tropicalis (C. tropicalis) is the third most common pathogen causing invasive candidiasis. Moreover, the majority of fluconazole-resistant C. tropicalis isolates were from a single hospital. Therefore, a molecular epidemiological survey is necessary to investigate the genetic relatedness of C. tropicalis isolates in China., Methods: In this study, 48 C. tropicalis isolates causing invasive fungal infections from four tertiary hospitals in China were studied. All the isolates were identified by sequencing the internal transcribed spacer region. Antifungal susceptibility to triazoles, amphotericin B, and caspofungin was determined by the Clinical and Laboratory Standards Institute standard broth microdilution method. Multilocus sequence typing (MLST) was performed, and phylogenetic analysis was further performed by the eBURST and maximum parsimony (MP) methods to characterize the genetic relatedness of isolates., Results: MLST discriminated 40 diploid sequence types (DSTs) among 48 isolates, including 36 novel DSTs, and the XYR1 gene showed the highest discriminatory power. The DSTs obtained from this study were compared with those of previously reported C. tropicalis isolates, and there was poor type alignment with regional strains. Nine groups and 11 singletons were identified by eBURST, whereas two groups and 10 subgroups were clustered by MP analysis. Generally, there were no obvious correlations between clonal clusters generated and the specimen source or hospital origin. Seven fluconazole-resistant isolates were confirmed and assigned to three distinguishable branches., Conclusions: The results suggested diverse origins of invasive C. tropicalis isolates in China. Although most invasive C. tropicalis strains in the mainland of China were clustered with previously characterized Asian isolates, major C. tropicalis clusters identified in this study were genetically distinct from those of other geographic regions.

Although Candida tropicalis is a frequent cause of invasive fungal diseases, its interaction with the host remains poorly studied. Galleria mellonella is a Lepidoptera model which offers a useful tool to study virulence of different microorganisms and drug efficacy. In this work we investigated the virulence of C. tropicalis in G. mellonella at different temperatures and the efficacy of antifungal drugs in this infection model. When larvae were infected with yeast inocula suspensions of different concentrations (4 × 10(6), 2 × 10(6), 10(6) and 5 × 10(5) cells/larva), we observed a dose-dependent effect on the killing of the insect (50% survival ranging from 1.4 ± 0.8 to 8.8 ± 1.2 days with the higher and lower inocula, respectively). Candida tropicalis killed G. mellonella larvae at both 30°C and 37°C, although at 37°C the virulence was more evident. Haemocytes phagocytosed C. tropicalis cells after 2 hours of infection, although the phagocytosis rate was lower when compared with other fungal pathogens, such as Cryptococcus neoformans. Moreover, the haemocyte density in the haemolymph decreased during infection and the yeast formed pseudohyphae in G. mellonella. The efficacy of amphotericin B, caspofungin, fluconazole and voriconazole was tested at different concentrations, and a protective effect was observed with all the drugs at concentrations equivalent to therapeutic dose. Fungal burden increased in infected larvae during time of infection and amphotericin B and fluconazole reduced the number of colony-forming units in the worms. Moreover, antifungal treatment was associated with the presence of cell aggregates around infected areas. We conclude that G. mellonella offers a simple and feasible model to study C. tropicalis virulence and drug efficacy.

There have recently been significant increases in the prevalence of systemic invasive fungal infections. However, the number of antifungal drugs on the market is limited in comparison to the number of available antibacterial drugs. This fact, coupled with the increased frequency of cross-resistance, makes it necessary to develop new therapeutic strategies. Combination drug therapies have become one of the most widely used and effective strategies to alleviate this problem. Amiodarone (AMD) is classically used for the treatment of atrial fibrillation and is the drug of choice for patients with arrhythmia. Recent studies have shown broad antifungal activity of the drug when administered in combination with fluconazole (FLC). In the present study, we induced resistance to fluconazole in six strains of Candida tropicalis and evaluated potential synergism between fluconazole and amiodarone. The evaluation of drug interaction was determined by calculating the fractional inhibitory concentration and by performing flow cytometry. We conclude that amiodarone, when administered in combination with fluconazole, exhibits activity against strains of C. tropicalis that are resistant to fluconazole, which most likely occurs via changes in the integrity of the yeast cell membrane and the generation of oxidative stress, mitochondrial dysfunction, and DNA damage that could lead to cell death by apoptosis.

Candida tropicalis is considered the first or the second non-Candida albicans Candida (NCAC) species most frequently isolated from candidosis, mainly in patients admitted in intensive care units (ICUs), especially with cancer, requiring prolonged catheterization, or receiving broad-spectrum antibiotics. The proportion of candiduria and candidemia caused by C. tropicalis varies widely with geographical area and patient group. Actually, in certain countries, C. tropicalis is more prevalent, even compared with C. albicans or other NCAC species. Although prophylactic treatments with fluconazole cause a decrease in the frequency of candidosis caused by C. tropicalis, it is increasingly showing a moderate level of fluconazole resistance. The propensity of C. tropicalis for dissemination and the high mortality associated with its infections might be strongly related to the potential of virulence factors exhibited by this species, such as adhesion to different host surfaces, biofilm formation, infection and dissemination, and enzymes secretion. Therefore, the aim of this review is to outline the present knowledge on all the above-mentioned C. tropicalis virulence traits.

The intestinal microflora, typically equated with bacteria, influences diseases such as obesity and inflammatory bowel disease. Here, we show that the mammalian gut contains a rich fungal community that interacts with the immune system through the innate immune receptor Dectin-1. Mice lacking Dectin-1 exhibited increased susceptibility to chemically induced colitis, which was the result of altered responses to indigenous fungi. In humans, we identified a polymorphism in the gene for Dectin-1 (CLEC7A) that is strongly linked to a severe form of ulcerative colitis. Together, our findings reveal a eukaryotic fungal community in the gut (the "mycobiome") that coexists with bacteria and substantially expands the repertoire of organisms interacting with the intestinal immune system to influence health and disease.