Candida and Staph cooperate to resist antimicrobials
More evidence that multispecies biofilms are a force to be reckoned with. But there is a bright side.
An interesting paper just came out in mBio reiterating the message that multispecies biofilms need to be taken seriously in the clinic. Specifically, they showed that the Candida extracellular matrix protects Staphylococcus aureus cells from antimicrobials like vancomycin (the last line antibiotic for many gram positives).
It's not all doom and gloom though. They also show that using antifungals reverses the protective effect and senstitises the S. aureus cells again. This means that if multispecies biofilms can be identified early enough as the cause of an infection, treatment can be swift and effective.
Rapid diagnostics for Candida and Staph anyone? Read more details below and let me know what you think in the comments.
Biofilm-associated polymicrobial infections, particularly those involving fungi and bacteria, are responsible for significant morbidity and mortality and tend to be challenging to treat. Candida albicans and Staphylococcus aureus specifically are considered leading opportunistic fungal and bacterial pathogens, respectively, mainly due to their ability to form biofilms on catheters and indwelling medical devices. However, the impact of mixed-species biofilm growth on therapy remains largely understudied. In this study, we investigated the influence of C. albicans secreted cell wall polysaccharides on the response of S. aureus to antibacterial agents in biofilm. Results demonstrated significantly enhanced tolerance for S. aureus to drugs in the presence of C. albicans or its secreted cell wall polysaccharide material. Fluorescence confocal time-lapse microscopy revealed impairment of drug diffusion through the mixed biofilm matrix. Using C. albicans mutant strains with modulated cell wall polysaccharide expression, exogenous supplementation, and enzymatic degradation, the C. albicans-secreted β-1,3-glucan cell wall component was identified as the key matrix constituent providing the bacteria with enhanced drug tolerance. Further, antibody labeling demonstrated rapid coating of the bacteria by the C. albicans matrix material. Importantly, via its effect on the fungal biofilm matrix, the antifungal caspofungin sensitized the bacteria to the drugs. Understanding such symbiotic interactions with clinical relevance between microbial species in biofilms will greatly aid in overcoming the limitations of current therapies and in defining potential new targets for treating polymicrobial infections.
The fungus Candida albicans and the bacterium Staphylococcus aureus are important microbial pathogens responsible for the majority of infections in hospitalized patients and are often coisolated from a host. In this study, we demonstrated that when grown together, the fungus provides the bacterium with enhanced tolerance to antimicrobial drugs. This process was mediated by polysaccharides secreted by the fungal cell into the environment. The biofilm matrix formed by these polysaccharides prevented penetration by the drugs and provided the bacteria with protection. Importantly, we show that by inhibiting the production of the fungal polysaccharides, a specific antifungal agent indirectly sensitized the bacteria to antimicrobials. Understanding the therapeutic implications of the interactions between these two diverse microbial species will aid in overcoming the limitations of current therapies and in defining new targets for treating complex polymicrobial infections.
Kong EF, Tsui C, Kucharíková S, Andes D, Van Dijck P, Jabra-Rizk MA. 2016. Commensal protection of Staphylococcus aureus against antimicrobials by Candida albicans biofilm matrix. mBio 7(5):e01365-16. doi:10.1128/mBio.01365-16.