Staphylococci and C. albicans are the most frequent combination of organisms isolated from polymicrobial infections. The ability of C. albicans and S. aureus to cause disease largely depends on their ability to form biofilms and alter their transcriptome in response to different stresses to ensure survival in the host. Changes in the transcriptional network also ensure that these organisms can grow in tissues and survive stresses inflicted upon them by cells of the innate immune system. Significantly, enhanced in vitro tolerance to antimicrobials in C. albicans and staphylococci mixed biofilms has been reported. Consequently, in addition to formation of enhanced and persistent biofilms, co-infection with S. aureus and C. albicans may influence gene expression, in turn impacting virulence and drug resistance. Therefore, it has become imperative to elucidate the unique interactions between these pathogens within polymicrobial biofilms in vivo with the goal of providing overall insights into the dynamics of how mixed- microbial populations are established and regulated in the human body. To that end, we developed a practical and clinically-relevant subcutaneous catheter mouse model to characterize the molecular interplay between S. aureus and C. albicans as they co- infect a host by performing comparative transcriptomics analysis of single and mixed- species biofilms. Further, we designed feasible non-invasive bioluminescence imaging and intravital microscopy systems as tools, which we will use to elucidate the mechanisms of biofilm formation and development of drug resistance under in vivo conditions. Our central hypothesis is that the regulatory and transcriptional pathways uniquely expressed during in vivo-grown polymicrobial biofilms of C. albicans and S. aureus identify microbial phenotypes of enhanced pathogenic potential central to the persistence and antimicrobial resistance of biofilm-associated polymicrobial infections.
Biofilm-associated polymicrobial infections caused by combinations of microorganisms are associated with the presence of catheters and other indwelling medical devices. Candida albicans and Staphylococcus aureus are the most commonly co-isolated human pathogens largely due to their ability to adhere to biotic and abiotic surfaces. In this proposal we will use a clinically relevant subcutaneous catheter mouse model to study in vivo-grown S. aureus and C. albicans biofilm infections using global transcriptomic analysis and mutant strains. Further, bioluminescence imaging and intravital microscopy will be used as tools to elucidate mechanisms of biofilm formation and development of drug resistance under in vivo conditions. The accomplishment of the proposed work may lead to the identification of novel drug targets or alter current treatment strategies for those infected with complex polymicrobial infections.
| Kong, Eric F; Tsui, Christina; Kucharíková, Sona et al. (2017) Modulation of Staphylococcus aureus Response to Antimicrobials by the Candida albicans Quorum Sensing Molecule Farnesol. Antimicrob Agents Chemother 61: |
| Kong, Eric F; Johnson, Jennifer K; Jabra-Rizk, Mary Ann (2016) Community-Associated Methicillin-Resistant Staphylococcus aureus: An Enemy amidst Us. PLoS Pathog 12:e1005837 |
| Kong, Eric F; Tsui, Christina; Kucharíková, Sona et al. (2016) Commensal Protection of Staphylococcus aureus against Antimicrobials by Candida albicans Biofilm Matrix. MBio 7: |
