AUTHOR=Eichelberger Kara R. , Cassat James E. 

TITLE=Metabolic Adaptations During Staphylococcus aureus and Candida albicans Co-Infection

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.797550

DOI=10.3389/fimmu.2021.797550

ISSN=1664-3224

ABSTRACT=<p>Successful pathogens require metabolic flexibility to adapt to diverse host niches. The presence of co-infecting or commensal microorganisms at a given infection site can further influence the metabolic processes required for a pathogen to cause disease. The Gram-positive bacterium <italic>Staphylococcus aureus</italic> and the polymorphic fungus <italic>Candida albicans</italic> are microorganisms that asymptomatically colonize healthy individuals but can also cause superficial infections or severe invasive disease. Due to many shared host niches, <italic>S. aureus</italic> and <italic>C. albicans</italic> are frequently co-isolated from mixed fungal-bacterial infections. <italic>S. aureus</italic> and <italic>C. albicans</italic> co-infection alters microbial metabolism relative to infection with either organism alone. Metabolic changes during co-infection regulate virulence, such as enhancing toxin production in <italic>S. aureus</italic> or contributing to morphogenesis and cell wall remodeling in <italic>C. albicans</italic>. <italic>C. albicans</italic> and <italic>S. aureus</italic> also form polymicrobial biofilms, which have greater biomass and reduced susceptibility to antimicrobials relative to mono-microbial biofilms. The <italic>S. aureus</italic> and <italic>C. albicans</italic> metabolic programs induced during co-infection impact interactions with host immune cells, resulting in greater microbial survival and immune evasion. Conversely, innate immune cell sensing of <italic>S. aureus</italic> and <italic>C. albicans</italic> triggers metabolic changes in the host cells that result in an altered immune response to secondary infections. In this review article, we discuss the metabolic programs that govern host-pathogen interactions during <italic>S. aureus</italic> and <italic>C. albicans</italic> co-infection. Understanding <italic>C. albicans-S. aureus</italic> interactions may highlight more general principles of how polymicrobial interactions, particularly fungal-bacterial interactions, shape the outcome of infectious disease. We focus on how co-infection alters microbial metabolism to enhance virulence and how infection-induced changes to host cell metabolism can impact a secondary infection.</p>