Abstract
Fungal pathogens pose a severe danger to public health, with more than one billion invasive and superficial fungal infections and about 1.5 million related deaths per year, globally. Candida auris is a newly emerged fungal pathogen, that is known for its ability to cause severe invasive infections. This pathogen has been linked to outbreaks in hospital environments, a trait that is unusual for fungal pathogens. The incidence and geographic range of the pathogen also presents virulence factors and the ability to withstand elevated temperature and saline environments. The advent of multidrug-resistant non-albican Candida strains like C. auris against the currently available antifungal drugs in the clinical pipeline presents a severe hazard to the global health settings. Thus, to counteract the evolving multidrug-resistant issue, early drug discovery initiatives need to be strengthened to develop antifungal drug candidates that can alleviate the antifungal drug paucity challenge. The current study aimed to characterize the susceptibility patterns and virulence factors of C. auris. We also aimed to expand the treatment options by evaluating the potential of fungal secondary metabolites as effective therapeutic agents against C. auris. A total of 15 C. auris isolates were selected for this study. These were first examined for susceptibility to three major antifungal drugs classes (azoles, polyenes and echinocandins). We also characterized selected virulence factors including the production of extracellular enzymes (phospholipase and proteinase), chlamydospore formation, adherence, and biofilm formation. The five C. auris isolates showing high resistance and virulence factors were further tested for their ability to tolerate high temperature and salinity conditions and also for the production of extracellular enzymes at a temperature of 42°C. Lastly, we identified an endophytic isolate, Akanthomyces muscarius, that produced extracts with antifungal activity against C. auris isolates that were resistant to all other drugs tested. The ability of endophytic fungi to synthesize secondary metabolites that exhibit antimicrobial activity against multidrug-resistant pathogens suggest a potential alternative therapeutic approach to expand the range of available treatment options.
Keywords: Candida auris, antifungal susceptibility patterns,virulence factors, secondary metabolites.