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Immunol."],"abstract":"<jats: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 <jats:italic>Staphylococcus aureus<\/jats:italic> and the polymorphic fungus <jats:italic>Candida albicans<\/jats:italic> are microorganisms that asymptomatically colonize healthy individuals but can also cause superficial infections or severe invasive disease. Due to many shared host niches, <jats:italic>S. aureus<\/jats:italic> and <jats:italic>C. albicans<\/jats:italic> are frequently co-isolated from mixed fungal-bacterial infections. <jats:italic>S. aureus<\/jats:italic> and <jats:italic>C. albicans<\/jats: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 <jats:italic>S. aureus<\/jats:italic> or contributing to morphogenesis and cell wall remodeling in <jats:italic>C. albicans<\/jats:italic>. <jats:italic>C. albicans<\/jats:italic> and <jats:italic>S. aureus<\/jats:italic> also form polymicrobial biofilms, which have greater biomass and reduced susceptibility to antimicrobials relative to mono-microbial biofilms. The <jats:italic>S. aureus<\/jats:italic> and <jats:italic>C. albicans<\/jats: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 <jats:italic>S. aureus<\/jats:italic> and <jats:italic>C. albicans<\/jats: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 <jats:italic>S. aureus<\/jats:italic> and <jats:italic>C. albicans<\/jats:italic> co-infection. Understanding <jats:italic>C. albicans-S. aureus<\/jats: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.<\/jats:p>","DOI":"10.3389\/fimmu.2021.797550","type":"journal-article","created":{"date-parts":[[2021,12,8]],"date-time":"2021-12-08T04:45:13Z","timestamp":1638938713000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":67,"title":["Metabolic Adaptations During Staphylococcus aureus and Candida albicans Co-Infection"],"prefix":"10.3389","volume":"12","author":[{"given":"Kara R.","family":"Eichelberger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James 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