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Polymicrobial endocarditis is uncommon, and polymicrobial endocarditis in combination with Coxiella burnetii is very rare. We herein describe an extremely rare case of polymicrobial bivalvular endocarditis due to coinfection with Enterococcus faecalis and Coxiella burnetii in a 62-year-old male patient, and extensively review the relevant medical literature. To the best of our knowledge, only three similar cases have been previously reported. Q fever is a worldwide endemic bacterial zoonosis, but it and its most common chronic complication, endocarditis, are still underestimated and underdiagnosed worldwide. This situation reflects the paucity of reported cases of polymicrobial endocarditis in combination with Coxiella burnetii. Clinical presentation of Q fever endocarditis is highly nonspecific, and diagnosis may be delayed or missed, leading to severe and potentially fatal disease. Our case and the previously reported similar cases emphasize the need for further evaluation of infective endocarditis due to Coxiella burnetii, in all cases of culture-negative endocarditis, and in prolonged oligo-symptomatic inflammatory syndrome, particularly in the presence of valvular heart disease. This approach should be applied even when typical pathogens are isolated, especially in endemic areas of Q fever, and with atypical presentation. [ABSTRACT FROM AUTHOR]

A retrospective descriptive study included patients admitted with severe burns over the course of 10 years (2008–2018). Across all patients, there were 39 different species of bacteria, with 23 species being Gram-negative and 16 being Gram-positive bacteria, with also five different species of fungi cultured. Pseudomonas aeruginosa was the most commonly isolated organism, with 57.45% of patients having a positive culture. There was a significant difference in the number of P. aeruginosa isolated from patients that acquired their burns at work, in a garden, inside a vehicle, in a garage or in a public place. In patients that were positive for P. aeruginosa, the number of operations was higher (2.4) and the length of stay was significantly increased (80.1 days). Patients that suffered from substance abuse demonstrated significantly higher numbers of isolated P. aeruginosa (14.8%). Patients that suffered from both mental health illness and substance abuse demonstrated significantly higher numbers of P. aeruginosa isolated (18.5%). In the P. aeruginosa-negative group, there were significantly fewer patients that had been involved in a clothing fire. Furthermore, in the P. aeruginosa-negative patient cohort, the mortality rate was significantly higher (p = 0.002). Since the incidence of P. aeruginosa was also associated with a decreased mortality rate, it may be that patients admitted to hospital for shorter periods of time were less likely to be colonised with P. aeruginosa. This study demonstrates novel factors that may increase the incidence of P. aeruginosa isolated from burn patients. [ABSTRACT FROM AUTHOR]

Proteus mirabilis is a common uropathogen and a leading cause of catheter-associated urinary tract infections (CAUTIs), which are often polymicrobial. Through a genome-wide screen, we previously identified two [NiFe] hydrogenases as candidate fitness factors for P. mirabilis CAUTI: a Hyb-type Group 1c H2-uptake hydrogenase and a Hyf-type Group 4a H2-producing hydrogenase. In this study, we disrupted one gene of each system (hyfE and hybC) and also generated a double mutant to examine the contribution of flexible H2 metabolism to P. mirabilis growth and fitness in vitro and during experimental CAUTI. Since P. mirabilis is typically present as part of a polymicrobial community in the urinary tract, we also examined the impact of two common co-colonization partners, Providencia stuartii and Enterococcus faecalis, on the expression and contribution of each hydrogenase to fitness. Our data demonstrate that neither system alone is critical for P. mirabilis growth in vitro or fitness during experimental CAUTI. However, perturbation of flexible H2 metabolism in the ∆hybC∆hyfE double mutant decreased P. mirabilis fitness in vitro and during infection. The Hyf system alone contributed to the generation of proton motive force and swarming motility, but only during anaerobic conditions. Unexpectedly, both systems contributed to benzyl viologen reduction in TYET medium, and disruption of either system increased expression of the other. We further demonstrate that polymicrobial interactions with P. stuartii and E. faecalis alter the expression of Hyb and Hyf in vitro as well as the contribution of each system to P. mirabilis fitness during CAUTI. [ABSTRACT FROM AUTHOR]

The checkerboard assay is a well-established tool used to determine the antimicrobial effects of two compounds in combination. Usually, data collected from the checkerboard assay use visible turbidity and optical density as a readout. While helpful in traditional checkerboard assays, these measurements become less useful in a polymicrobial context as they do not enable assessment of the drug effects on the individual members of the community. The methodology described herein allows for the determination of cell viability through selective and differential plating of each individual species in a community while retaining much of the high-throughput nature of a turbidity-based analysis and requiring no specialized equipment. This methodology further improves turbidity-based measurements by providing a distinction between bacteriostatic versus bactericidal concentrations of antibiotics. Herein, we use this method to demonstrate that the clinically used antibiotic combination of ceftazidime and gentamicin works synergistically against Pseudomonas aeruginosa in monoculture but antagonistically in a polymicrobial culture also containing Acinetobacter baumannii, Staphylococcus aureus, and Enterococcus faecalis, highlighting the fundamental importance of this methodology in improving clinical practices. We propose that this method could be implemented in clinical microbiology laboratories with minimal impact on the overall time for diagnosis. [ABSTRACT FROM AUTHOR]

VAP due to multidrug-resistant (MDR) bacteria is a frequent infection among patients in ICUs. Patient characteristics and mortality in mono- and polybacterial cases of VAP may differ. A single-centre, retrospective 3-year study was conducted in the four ICUs of a Lithuanian referral university hospital, aiming to compare both the clinical features and the 60-day ICU all-cause mortality of monobacterial and polybacterial MDR Klebsiella spp. VAP episodes. Of the 86 MDR Klebsiella spp. VAP episodes analyzed, 50 (58.1%) were polybacterial. The 60-day mortality was higher (p < 0.05) in polybacterial episodes: overall (50.0 vs. 27.8%), in the sub-group with less-severe disease (SOFA < 8) at VAP onset (45.5 vs. 15.0%), even with appropriate treatment (41.7 vs. 12.5%), and the sub-group of extended drug-resistant (XDR) Klebsiella spp. (46.4 vs. 17.6%). The ICU mortality (44.0 vs. 22.5%) was also higher in the polybacterial episodes. The monobacterial MDR Klebsiella spp. VAP was associated (p < 0.05) with prior hospitalization (61.1 vs. 40.0%), diabetes mellitus (30.6 vs. 5.8%), obesity (30.6 vs. 4.7%), prior antibiotic therapy (77.8 vs. 52.0%), prior treatment with cephalosporins (66.7 vs. 36.0%), and SOFA cardiovascular ≥ 3 (44.4 vs. 10.0%) at VAP onset. Patients with polybacterial VAP were more likely (p < 0.05) to be comatose (22.2 vs. 52.0%) and had a higher SAPS II score (median [IQR] 45.0 [35.25–51.1] vs. 50.0 [40.5–60.75]) at VAP onset. Polybacterial MDR Klebsiella spp. VAP had distinct demographic and clinical characteristics compared to monobacterial, and was associated with poorer outcomes. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to explore the clinical value of metagenomic next-generation sequencing (mNGS) in the diagnosis of polymicrobial periprosthetic joint infection (PJI). Methods: Patients with complete data who underwent surgery at our hospital between July 2017 and January 2021 for suspected periprosthetic joint infection (PJI), according to the 2018 ICE diagnostic criteria, were enrolled, and all patients underwent microbial culture and mNGS detection, which were performed on the BGISEQ-500 platform. Microbial cultures were performed on two samples of synovial fluid, six samples of tissue, and two samples of prosthetic sonicate fluid for each patient. The mNGS was performed on 10 tissues, 64 synovial fluid samples, and 17 prosthetic sonicate fluid samples. The results of mNGS testing were based on the interpretation of mNGS results in the previous literature and the assertions of microbiologists and orthopedic surgeons. The diagnostic efficacy of mNGS in polymicrobial PJI was assessed by comparing the results of conventional microbial cultures and mNGS. Results: A total of 91 patients were finally enrolled in this study. The sensitivity, specificity, and accuracy of conventional culture for the diagnosis of PJI were 71.0%, 95.4%, and 76.9%, respectively. The sensitivity, specificity, and accuracy of mNGS for the diagnosis of PJI were 91.3%, 86.3%, and 90.1%, respectively. The sensitivity, specificity, and accuracy of conventional culture for the diagnosis of polymicrobial PJI were 57.1%, 100%, and 91.3%, respectively. mNGS had a sensitivity, specificity, and accuracy of 85.7%, 60.0%, and 65.2%, respectively, for the diagnosis of polymicrobial PJI. Conclusions: mNGS can improve the diagnosis efficiency of polymicrobial PJI, and the combination of culture and mNGS is a promising method to diagnose polymicrobial PJI. [ABSTRACT FROM AUTHOR]

Edwardsiella ictaluri and Flavobacterium covae are pervasive bacterial pathogens associated with significant losses in catfish aquaculture. Bacterial coinfections have the potential to increase outbreak severity and can worsen on-farm mortality. A preliminary assessment of in vivo bacterial coinfection with E. ictaluri (S97-773) and F. covae (ALG-00-530) was conducted using juvenile channel catfish (Ictalurus punctatus). Catfish were divided into five treatment groups: (1) mock control; (2) E. ictaluri full dose (immersion; 5.4 × 105 CFU mL−1); (3) F. covae full dose (immersion; 3.6 × 106 CFU mL−1); (4) E. ictaluri half dose (immersion; 2.7 × 105 CFU mL−1) followed by half dose F. covae (immersion; 1.8 × 106 CFU mL−1); and (5) F. covae half dose followed by half dose E. ictaluri. In the coinfection challenges, the second inoculum was delivered 48 h after the initial exposure. At 21 days post-challenge (DPC), the single dose E. ictaluri infection yielded a cumulative percent mortality (CPM) of 90.0 ± 4.1%, compared with 13.3 ± 5.9% in the F. covae group. Mortality patterns in coinfection challenges mimicked the single dose E. ictaluri challenge, with CPM of 93.3 ± 5.4% for fish initially challenged with E. ictaluri followed by F. covae, and 93.3 ± 2.7% for fish exposed to F. covae and subsequently challenged with E. ictaluri. Despite similarities in the final CPM within the coinfection groups, the onset of peak mortality was delayed in fish exposed to F. covae first but was congruent with mortality trends in the E. ictaluri challenge. Catfish exposed to E. ictaluri in both the single and coinfected treatments displayed increased serum lysozyme activity at 4-DPC (p < 0.001). Three pro-inflammatory cytokines (il8, tnfα, il1β) were evaluated for gene expression, revealing an increase in expression at 7-DPC in all E. ictaluri exposed treatments (p < 0.05). These data enhance our understanding of the dynamics of E. ictaluri and F. covae coinfections in US farm-raised catfish. [ABSTRACT FROM AUTHOR]

Understanding chronic wound infection is key for successful treatment and requires accurate laboratory models. We describe a modified biofilm flow device that effectively mimics the chronic wound environment, including simulated wound fluid, a collagen-based 3D biofilm matrix, and a five-species mixture of clinically relevant bacteria (Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, and Citrobacter freundii). Mixed biofilms were cultured for between 3 and 14 days with consistent numbers of bacteria that exhibited reduced metabolic activity, which increased with a high dose of glucose. S. aureus was recovered from biofilms as a small colony variant, but as a normal colony variant if P. aeruginosa was excluded from the system. Bacteria within the biofilm did not co-aggregate but formed discrete, species-specific clusters. Biofilms demonstrated differential tolerance to the topical antimicrobials Neosporin and HOCl, consistent with protection due to the biofilm lifestyle. The characteristics exhibited within this model match those of real-world wound biofilms, reflecting the clinical scenario and yielding a powerful in vitro tool that is versatile, inexpensive, and pivotal for understanding chronic wound infection. [ABSTRACT FROM AUTHOR]

Biofilms are population of cells growing in a coordinated manner and exhibiting resistance towards hostile environments. The infections associated with biofilms are difficult to control owing to the chronicity of infections and the emergence of antibiotic resistance. Most microbial infections are contributed by polymicrobial or mixed species interactions, such as those observed in chronic wound infections, otitis media, dental caries, and cystic fibrosis. This review focuses on the polymicrobial interactions among bacterial-bacterial, bacterial-fungal, and fungal-fungal aggregations based on in vitro and in vivo models and different therapeutic interventions available for polymicrobial biofilms. Deciphering the mechanisms of polymicrobial interactions and microbial diversity in chronic infections is very helpful in anti-microbial research. Together, we have discussed the role of metagenomic approaches in studying polymicrobial biofilms. The outstanding progress made in polymicrobial research, especially the model systems and application of metagenomics for detecting, preventing, and controlling infections, are reviewed. [ABSTRACT FROM AUTHOR]

Objective: To provide an evaluation of incidence and six-month mortality rates of polymicrobial Staphylococcus aureus bacteremia (p-SAB) in the United States (US). Methods: A retrospective population-based study of all incident adults with monomicrobial SAB (m-SAB) and p-SAB in Olmsted County, Minnesota (MN) from 1 January 2006, through 31 December 2020, was conducted. Demographics, clinical characteristics, in-hospital outcomes, and six-month survival were compared between groups. Results: Overall, 31 incident p-SAB cases occurred during the 15-year study period, corresponding to an overall age- and sex-standardized incidence rate of 1.9/100,000 person-years (95% CI, 1.3–2.6). One-third of p-SAB cases were due to MRSA, and almost one-half (15/31) were caused by Gram-positive bacteria. As compared to the 541 cases with incident m-SAB, p-SAB patients were more likely to have a catheter-related infection (p = 0.008) and less likely to be community-acquired cases (p = 0.027). The unadjusted risk of six-month mortality was greater in the p-SAB group (14/31, 45.2%) compared to the m-SAB group (144/541, 26.6%) (HR = 1.94, 95% CI = 1.12–3.36, p = 0.018). After adjusting for relevant covariates, this difference approached significance (HR = 1.93, 95% = CI 0.96–3.87, p = 0.064). Conclusions: To our knowledge, the current investigation represents the only US population-based study evaluating p-SAB patients. We found lower incidence rates for p-SAB than previously reported, with almost one-half of the cases caused by Gram-positive bacteria. Furthermore, these patients had poor survival compared to incident m-SAB cases. [ABSTRACT FROM AUTHOR]

Candida auris can persistently colonize human skin, alongside a diverse bacterial microbiome. In this study we aimed to investigate the efficacy of antiseptic activities on dual-species interkingdom biofilms containing staphylococci to determine if antiseptic tolerance was negatively impacted by dual-species biofilms. Chlorhexidine, povidone iodine, and hydrogen peroxide (H2O2), were able to significantly reduce biofilm viable cell counts following exposure at 2%, 10%, and 3%, respectively. Notably, H2O2-treated biofilms were able to significantly recover and considerably repopulate following treatment. Fortunately, inter-kingdom interactions in dual-species biofilms of C. auris and staphylococci did not increase the tolerance of C. auris against antiseptics in vitro. These data indicate mixed infections are manageable with chlorhexidine and povidone iodine, but caution should be exercised in the consideration of H2O2. [ABSTRACT FROM AUTHOR]

Multidrug-resistant A. baumannii (MDRAB) VAP has high morbidity and mortality, and the rates are constantly increasing globally. Mono- and polybacterial MDRAB VAP might differ, including outcomes. We conducted a single-center, retrospective (January 2014–December 2016) study in the four ICUs (12–18–24 beds each) of a reference Lithuanian university hospital, aiming to compare the clinical features and the 30-day mortality of monobacterial and polybacterial MDRAB VAP episodes. A total of 156 MDRAB VAP episodes were analyzed: 105 (67.5%) were monomicrobial. The 30-day mortality was higher (p < 0.05) in monobacterial episodes: overall (57.1 vs. 37.3%), subgroup with appropriate antibiotic therapy (50.7 vs. 23.5%), and subgroup of XDR A. baumannii (57.3 vs. 36.4%). Monobacterial MDRAB VAP was associated (p < 0.05) with Charlson comorbidity index ≥3 (67.6 vs. 47.1%), respiratory comorbidities (19.0 vs. 5.9%), obesity (27.6 vs. 9.8%), prior hospitalization (58.1 vs. 31.4%), prior antibiotic therapy (99.0 vs. 92.2%), sepsis (88.6 vs. 76.5%), septic shock (51.9 vs. 34.6%), severe hypoxemia (23.8 vs. 7.8%), higher leukocyte count on VAP onset (median [IQR] 11.6 [8.4–16.6] vs. 10.9 [7.3–13.4]), and RRT need during ICU stay (37.1 vs. 17.6%). Patients with polybacterial VAP had a higher frequency of decreased level of consciousness (p < 0.05) on ICU admission (29.4 vs. 14.3%) and on VAP onset (29.4 vs. 11.4%). We concluded that monobacterial MDRAB VAP had different demographic/clinical characteristics compared to polybacterial and carried worse outcomes. These important findings need to be validated in a larger, prospective study, and the management implications to be further investigated. [ABSTRACT FROM AUTHOR]

Most animal models of infection utilize planktonic bacteria as initial inocula. However, this may not accurately mimic scenarios where bacteria in the biofilm phenotype contaminate a site at the point of injury. We developed a modified CDC biofilm reactor in which biofilms can be grown on the surface of simulated fracture fixation plates. Multiple reactor runs were performed and demonstrated that monomicrobial biofilms of a clinical strain of methicillin-resistant Staphylococcus aureus, S. aureus ATCC 6538, and Pseudomonas aeruginosa ATCC 27853 consistently developed on fixation plates. We also identified a method by which to successfully grow polymicrobial biofilms of S. aureus ATCC 6538 and P. aeruginosa ATCC 27853 on fixation plates. This customized reactor can be used to grow biofilms on simulated fracture fixation plates that can be inoculated in animal models of biofilm implant-related infection that, for example, mimic open fracture scenarios. The reactor provides a method for growing biofilms that can be used as initial inocula and potentially improve the testing and development of antibiofilm technologies. [ABSTRACT FROM AUTHOR]

While Koch's Postulates have established rules for microbial pathogenesis that have been extremely beneficial for monomicrobial infections, new studies regarding polymicrobial pathogenesis defy these standards. The explosion of phylogenetic sequence data has revolutionized concepts of microbial interactions on and within the host. However, there remains a paucity of functional follow-up studies to delineate mechanisms driven by such interactions and how they shape health or disease. That said, one particular microbial pairing, the fungal opportunist Candida albicans and the bacterial pathogen Staphylococcus aureus, has received much attention over the last decade. Therefore, the objective of this review is to discuss the multi-faceted mechanisms employed by these two ubiquitous human pathogens during polymicrobial growth, including how they: establish and persist in inter-Kingdom biofilms, tolerate antimicrobial therapy, co-invade host tissue, exacerbate quorum sensing and staphylococcal toxin production, and elicit infectious synergism. Commentary regarding new challenges and remaining questions related to future discovery of this fascinating fungal-bacterial interaction is also provided. [ABSTRACT FROM AUTHOR]

Polymicrobial sepsis is difficult to diagnose and treat and causes significant morbidity and mortality, especially when fungi are involved. In vitro, synergism between Candida albicans and various bacterial species has been described for many years. Our laboratory has developed a murine model of polymicrobial intra-abdominal infection with Candida albicans and Staphylococcus aureus, demonstrating that polymicrobial infections cause high levels of mortality, while monoinfections do not. By contrast, closely related Candida dubliniensis does not cause synergistic lethality and rather provides protection against lethal polymicrobial infection. This protection is thought to be driven by a novel form of trained innate immunity mediated by myeloid-derived suppressor cells (MDSCs), which we are proposing to call "trained tolerogenic immunity". MDSC accumulation has been described in patients with sepsis, as well as in in vivo sepsis models. However, clinically, MDSCs are considered detrimental in sepsis, while their role in in vivo models differs depending on the sepsis model and timing. In this review, we will discuss the role of MDSCs in sepsis and infection and summarize our perspectives on their development and function in the spectrum of trained innate immune protection against fungal-bacterial sepsis. [ABSTRACT FROM AUTHOR]

Denture stomatitis (DS) is an inflammatory disease resulting from a polymicrobial biofilm perturbation at the denture surface–palatal mucosa interface. Recommendations made by dental health care professionals often lack clarity for appropriate denture cleaning. This study investigated the efficacy of brushing with off-the-shelf denture cleanser (DC) tablets (Poligrip®) vs. two toothpastes (Colgate® and Crest®) in alleviating the viable microorganisms (bacteria and fungi) in an in vitro denture biofilm model. Biofilms were grown on poly(methyl)methacrylate (PMMA) discs, then treated daily for 7 days with mechanical disruption (brushing), plus Poligrip® DC, Colgate® or Crest® toothpastes. Weekly treatment with Poligrip® DC on day 7 only was compared to daily modalities. All treatment parameters were processed to determine viable colony forming units for bacteria and fungi using the Miles and Misra technique, and imaged by confocal laser scanning microscopy (CLSM). Brushing with daily DC therapy was the most effective treatment in reducing the viable biofilm over 7 days of treatment. Brushing only was ineffective in controlling the viable bioburden, which was confirmed by CLSM imaging. This data indicates that regular cleansing of PMMA with DC was best for polymicrobial biofilms. [ABSTRACT FROM AUTHOR]

Here, we describe the validation of a new phenotypic culture-based AtbFinder method for rapid selection of antibiotics in vitro using specimens with mono- and polybacterial infections. AtbFinder, which can be applied to any type of non-blood tissue, does not require isolation of pure bacterial cultures. The method uses a novel TGV medium that allows more rapid bacterial growth of Gram-positive and Gram-negative monoisolates compared with that achieved with conventional laboratory media, demonstrating overall sensitivity, specificity, PPV, NPV values of 99.6%, 98.1%, 98.5%, and 99.4%, respectively, after 4 h. For polymicrobial infections, AtbFinder utilized a novel paradigm of the population response to antibiotics, enabling bacterial growth in the form of a mixed microbial community and selecting antibiotics targeting not only the principal pathogen, but also those bacteria that support their growth. TGV medium allowed culturing of a more diverse set of bacteria from polymicrobial biospecimens, compared with that achieved with the standard media, and enabled, within 4 h, accurate selection of the antibiotics that completely eliminated all cultivatable bacteria from clinical samples. In conclusion, the AtbFinder system may be a valuable tool in improving antibiotic selection, and enabling targeted empirical therapy and accurate antibiotic replacement, which is especially important in high-risk patients. [ABSTRACT FROM AUTHOR]

In recent years, the scientific community has focused on the development of new antibiotics to address the difficulties linked to biofilm-forming microorganisms and drug-resistant infections. In this respect, synthetic antimicrobial peptides (AMPs) are particularly regarded for their therapeutic potential against a broad spectrum of pathogens. In this work, the antimicrobial and antibiofilm activities of the peptide WMR-K towards single and dual species cultures of Candida albicans and Klebsiella pneumoniae were investigated. We found minimum inhibitory concentration (MIC) values for WMR-K of 10 µM for K. pneumoniae and of 200 µM for C. albicans. Furthermore, sub-MIC concentrations of peptide showed an in vitro inhibition of biofilm formation of mono and polymicrobial systems and also a good biofilm eradication even if higher concentrations of it are needed. In order to provide additional evidence for the effect of the examined peptide, a study of changes in extracellular metabolites excreted and/or uptaken from the culture medium (metabolomic footprinting) in the poly-microbial association of C. albicans and K. pneumoniae in presence and absence of WMR-K was performed. Comparing to the untreated dual species biofilm culture, the metabolomic profile of the WMR-K treated culture appears significantly altered. The differentially expressed compounds are mainly related to the primary metabolic pathways, including amino acids, trehalose, pyruvic acid, glycerol and vitamin B6. [ABSTRACT FROM AUTHOR]

With the development of next generation sequencing technologies in recent years, it has been demonstrated that many human infectious processes, including chronic wounds, cystic fibrosis, and otitis media, are associated with a polymicrobial burden. Research has also demonstrated that polymicrobial infections tend to be associated with treatment failure and worse patient prognoses. Despite the importance of the polymicrobial nature of many infection states, the current clinical standard for determining antimicrobial susceptibility in the clinical laboratory is exclusively performed on unimicrobial suspensions. There is a growing body of research demonstrating that microorganisms in a polymicrobial environment can synergize their activities associated with a variety of outcomes, including changes to their antimicrobial susceptibility through both resistance and tolerance mechanisms. This review highlights the current body of work describing polymicrobial synergism, both inter- and intra-kingdom, impacting antimicrobial susceptibility. Given the importance of polymicrobial synergism in the clinical environment, a new system of determining antimicrobial susceptibility from polymicrobial infections may significantly impact patient treatment and outcomes. [ABSTRACT FROM AUTHOR]

The immunocompromised airways are susceptible to infections caused by a range of pathogens which increases the opportunity for polymicrobial interactions to occur. Pseudomonas aeruginosa and Staphylococcus aureus are the predominant causes of pulmonary infection for individuals with respiratory disorders such as cystic fibrosis (CF). The spore-forming fungus Aspergillus fumigatus, is most frequently isolated with P. aeruginosa, and co-infection results in poor outcomes for patients. It is therefore clinically important to understand how these pathogens interact with each other and how such interactions may contribute to disease progression so that appropriate therapeutic strategies may be developed. Despite its persistence in the airways throughout the life of a patient, A. fumigatus rarely becomes the dominant pathogen. In vitro interaction studies have revealed remarkable insights into the molecular mechanisms that drive agonistic and antagonistic interactions that occur between A. fumigatus and pulmonary bacterial pathogens such as P. aeruginosa. Crucially, these studies demonstrate that although bacteria may predominate in a competitive environment, A. fumigatus has the capacity to persist and contribute to disease. [ABSTRACT FROM AUTHOR]

Fungal and bacterial species interact with each other within polymicrobial biofilm communities in various niches of the human body. Interactions between these species can greatly affect human health and disease. Diseases caused by polymicrobial biofilms pose a major challenge in clinical settings because of their enhanced virulence and increased drug tolerance. Therefore, different approaches are being explored to treat fungal–bacterial biofilm infections. This review focuses on the main mechanisms involved in polymicrobial drug tolerance and the implications of the polymicrobial nature for the therapeutic treatment by highlighting clinically relevant fungal–bacterial interactions. Furthermore, innovative treatment strategies which specifically target polymicrobial biofilms are discussed. [ABSTRACT FROM AUTHOR]

Background: Existing standardized biofilm assays focus on simple mono-species or bacterial-only models. Incorporating Candida albicans into complex biofilm models can offer a more appropriate and relevant polymicrobial biofilm for the development of oral health products. Aims: This study aimed to assess the importance of interkingdom interactions in polymicrobial oral biofilm systems with or without C. albicans, and test how these models respond to oral therapeutic challenges in vitro. Materials and Methods: Polymicrobial biofilms (two models containing 5 and 10 bacterial species, respectively) were created in parallel in the presence and absence of C. albicans and challenged using clinically relevant antimicrobials. The metabolic profiles and biomasses of these complex biofilms were estimated using resazurin dye and crystal violet stain, respectively. Quantitative PCR was utilized to assess compositional changes in microbial load. Additional assays, for measurements of pH and lactate, were included to monitor fluctuations in virulence "biomarkers." Results: An increased level of metabolic activity and biomass in the presence of C. albicans was observed. Bacterial load was increased by more than a factor of 10 in the presence of C. albicans. Assays showed inclusion of C. albicans impacted the biofilm virulence profiles. C. albicans did not affect the biofilms' responses to the short-term incubations with different treatments. Conclusions: The interkingdom biofilms described herein are structurally robust and exhibit all the hallmarks of a reproducible model. To our knowledge, these data are the first to test the hypothesis that yeasts may act as potential "keystone" components of oral biofilms. [ABSTRACT FROM AUTHOR]

Indwelling urinary catheters are common in health care settings and can lead to catheter-associated urinary tract infection (CAUTI). Long-term catheterization causes polymicrobial colonization of the catheter and urine, for which the clinical significance is poorly understood. Through prospective assessment of catheter urine colonization, we identified Enterococcus faecalis and Proteus mirabilis as the most prevalent and persistent co-colonizers. Clinical isolates of both species successfully co-colonized in a murine model of CAUTI, and they were observed to co-localize on catheter biofilms during infection. We further demonstrate that P. mirabilis preferentially adheres to E. faecalis during biofilm formation, and that contact-dependent interactions between E. faecalis and P. mirabilis facilitate establishment of a robust biofilm architecture that enhances antimicrobial resistance for both species. E. faecalis may therefore act as a pioneer species on urinary catheters, establishing an ideal surface for persistent colonization by more traditional pathogens such as P. mirabilis. [ABSTRACT FROM AUTHOR]

Fungi and bacteria encounter each other in various niches of the human body. There, they interact directly with one another or indirectly via the host response. In both cases, interactions can affect host health and disease. In the present review, we summarized current knowledge on fungal-bacterial interactions during their commensal and pathogenic lifestyle. We focus on distinct mucosal niches: the oral cavity, lung, gut, and vagina. In addition, we describe interactions during bloodstream and wound infections and the possible consequences for the human host. [ABSTRACT FROM AUTHOR]