Fungal biofilm resistance

Fungal biofilm infections have become increasingly recognised as a significant clinical problem. One of the major reasons behind this is the impact that these have upon treatment, as antifungal therapy often fails and surgical intervention is required. This places a large financial burden on health care providers. This paper aims to illustrate the importance of fungal biofilms, particularly Candida albicans, and discusses some of the key fungal biofilm resistance mechanisms that include, extracellular matrix (ECM), efflux pump activity, persisters, cell density, overexpression of drug targets, stress responses, and the general physiology of the cell. The paper demonstrates the multifaceted nature of fungal biofilm resistance, which encompasses some of the newest data and ideas in the field

Tolerance of Pseudomonas aeruginosa in in vitro biofilms to high level peracetic acid disinfection

Biofilm has been suggested as a cause of disinfection failures in flexible endoscopes where no lapses in the decontamination procedure can be identified. To test this theory, the activity of peracetic acid (PAA), one of the commonly used disinfectants in the reprocessing of flexible endoscopes, was evaluated against both planktonic and sessile communities of Pseudomonas aeruginosa. To investigate the ability of P. aeruginosa biofilm to survive high level PAA disinfection. The susceptibility of planktonic cells of P. aeruginosa and biofilms 24, 48, 96 and 192 h old to PAA was evaluated by estimating their viability using resazurin viability and plate count methods. The biomass of the P. aeruginosa biofilms was also quantified using crystal violet assay. Planktonic cells of P. aeruginosa were treated with 5 - 30 ppm concentration of PAA in the presence of 3.0 g/L of Bovine serum albumin (BSA) for 5 min. Biofilms of P. aeruginosa were also treated with various PAA concentrations (100 - 3000 ppm) for 5 min. Planktonic cells of P. aeruginosa were eradicated by 20 ppm of PAA, whereas biofilms showed an age dependent tolerance to PAA, and 96 h old biofilm was only eradicated at PAA concentration of 2500 ppm. 96 h old P. aeruginosa biofilm survives 5 min treatment with 2000 ppm of PAA, which is the working concentration used in some endoscope washer disinfectors. This implies that disinfection failure of flexible endoscopes could occur when biofilms are allowed to build up in the lumens of endoscopes

Gaining insights from Candida biofilm heterogeneity: one size does not fit all

Despite their clinical significance and substantial human health burden, fungal infections remain relatively under-appreciated. The widespread overuse of antibiotics and the increasing requirement for indwelling medical devices provides an opportunistic potential for the overgrowth and colonization of pathogenic Candida species on both biological and inert substrates. Indeed, it is now widely recognized that biofilms are a highly important part of their virulence repertoire. Candida albicans is regarded as the primary fungal biofilm forming species, yet there is also increasing interest and growing body of evidence for non-Candida albicans species (NCAS) biofilms, and interkingdom biofilm interactions. C. albicans biofilms are heterogeneous structures by definition, existing as three-dimensional populations of yeast, pseudo-hyphae, and hyphae, embedded within a self-produced extracellular matrix. Classical molecular approaches, driven by extensive studies of laboratory strains and mutants, have enhanced our knowledge and understanding of how these complex communities develop, thrive, and cause host-mediated damage. Yet our clinical observations tell a different story, with differential patient responses potentially due to inherent biological heterogeneity from specific clinical isolates associated with their infections. This review explores some of the recent advances made in an attempt to explore the importance of working with clinical isolates, and what this has taught us

Implications of antimicrobial combinations in complex wound biofilms containing fungi

Diabetic foot ulcer treatment currently focuses on targeting bacterial biofilms, while dismissing fungi. To investigate this we used an in vitro biofilm model containing bacteria and fungi, reflective of the wound environment, to test the impact of antimicrobials. Here we showed that while mono-treatment approaches influenced biofilm composition it had no discernible effect on overall quantity. Only by combining bacterial and fungal specific antibiotics were we able to decrease the biofilm bioburden, irrespective of composition

Surface disinfection challenges for Candida auris: an in-vitro study

The emerging pathogenic multidrug-resistant yeast Candida auris is an important source of healthcare-associated infections and of growing global clinical concern. The ability of this organism to survive on surfaces and withstand environmental stressors creates a challenge for eradicating it from hospitals. A panel of C. auris clinical isolates was evaluated on different surface environments against the standard disinfectant sodium hypochlorite and high-level disinfectant peracetic acid. C. auris was shown to selectively tolerate clinically relevant concentrations of sodium hypochlorite and peracetic acid in a surface-dependent manner, which may explain its ability to successfully persist within the hospital environment

Imagine, Interrupt, Innovate: Internationalising Teaching and Learning Practice

Internationalisation of the curriculum is a key research area at the intersection of teaching and learning. Increasing numbers of international students in Australian schools and tertiary institutions necessitate the reconceptualisation of curriculum to incorporate global perspectives and develop intercultural competencies of both students and teachers. Accordingly, this research project identified key discipline areas at Avondale College of Higher Education in which to perform pedagogical intervention with an internationalisation focus. Three lecturers undertook action research in the areas of Primary Education, Business and Theology, resulting in the production of culturallyinformed perspectives, increased cross-cultural awareness and the identification of areas for future research and innovation

A Prospective Surveillance Study of Candidaemia : Epidemiology, Risk Factors, Antifungal Treatment and Outcome in Hospitalized Patients

Funding This work was supported by the Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377/Z/11/Z. Data collection was supported by a grant from Pfizer. GR was also supported by a research fellowship grant from Gilead Sciences. The collection of the isolates was funded by a Gilead Fellowship to GR. Acknowledgments We are grateful to microbiology colleagues throughout Scotland for submitting isolates. Antimicrobial sensitivity testing was performed by the Mycology Reference Laboratory, Public Health England, Bristol.Peer reviewedPublisher PD

Biofilms formed by Candida albicans bloodstream isolates display phenotypic and transcriptional heterogeneity that are associated with resistance and pathogenicity

Background: Candida albicans infections have become increasingly recognised as being biofilm related. Recent studies have shown that there is a relationship between biofilm formation and poor clinical outcomes in patients infected with biofilm proficient strains. Here we have investigated a panel of clinical isolates in an attempt to evaluate their phenotypic and transcriptional properties in an attempt to differentiate and define levels of biofilm formation.<p></p> Results: Biofilm formation was shown to be heterogeneous; with isolates being defined as either high or low biofilm formers (LBF and HBF) based on different biomass quantification. These categories could also be differentiated using a cell surface hydrophobicity assay with 24 h biofilms. HBF isolates were more resistance to amphotericin B (AMB) treatment than LBF, but not voriconazole (VRZ). In a Galleria mellonella model of infection HBF mortality was significantly increased in comparison to LBF. Histological analysis of the HBF showed hyphal elements intertwined indicative of the biofilm phenotype. Transcriptional analysis of 23 genes implicated in biofilm formation showed no significant differential expression profiles between LBF and HBF, except for Cdr1 at 4 and 24 h. Cluster analysis showed similar patterns of expression for different functional classes of genes, though correlation analysis of the 4 h biofilms with overall biomass at 24 h showed that 7 genes were correlated with high levels of biofilm, including Als3, Eap1, Cph1, Sap5, Plb1, Cdr1 and Zap1.<p></p> Conclusions: Our findings show that biofilm formation is variable amongst C. albicans isolates, and categorising isolates depending on this can be used to predict how pathogenic the isolate will behave clinically. We have shown that looking at individual genes in less informative than looking at multiple genes when trying to categorise isolates at LBF or HBF. These findings are important when developing biofilm-specific diagnostics as these could be used to predict how best to treat patients infected with C. albicans. Further studies are required to evaluate this clinically.<p></p&gt

Biofilm formation is a risk factor for mortality in patients with Candida albicans bloodstream infection-Scotland, 2012-2013

Acknowledgements This work was supported by the Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377/Z/11/Z. Data collection was supported by a grant from Pfizer. G. Ramage was also supported by a research fellowship grant from Gilead Sciences. We are grateful to microbiology colleagues throughout Scotland for submitting isolates.Peer reviewedPublisher PD

Virtual Delivery of Stress Management and Resiliency Training (SMART) During the COVID-19 Pandemic to Hematology/Oncology Fellows: A Pilot Study

Introduction: Medical trainees experience a high degree of stress that predisposes them to burnout. This pilot study tested a scalable approach to deliver a validated resilience program (Stress Management and Resiliency Training (SMART)) among Hematology/Oncology fellows at an academic medical center. Methods: This was a mixed-methods, prospective, single-arm clinical trial involving Hematology/Oncology fellows at Mayo Clinic in Rochester, MN, USA. Four one-hour training sessions were conducted virtually with 26 fellows. Stress, burnout, and emotional resilience were measured at baseline, three months, and six months post-intervention using the Perceived Stress Scale (PSS-10), Maslach Burnout Inventory (MBI-HSS), and Connor-Davidson Resilience Scale (CD-RISC2). Changes in mean scores were assessed using paired t-tests. Feasibility and acceptability data were obtained during a virtual focus group. Results: Statistically significant improvements in mean stress (p = 0.004) and professional achievement (p \u3c 0.001) were seen at three months post-intervention. At six months post-intervention, mean stress (p \u3c 0.001) and professional achievement (p = 0.032) continued to improve, while improvements in emotional exhaustion (p = 0.001) and depersonalization (p \u3c 0.001) also became significant. Focus group participants found the program beneficial and reported improved stress and work performance as a result of participation. Conclusion: Virtual implementation of the SMART program is feasible and resulted in improvements in stress and burnout. Focus group participants found the training beneficial, reporting lower stress and improved work performance