title: Inter- and intraspecies metabolite exchange promotes virulence of antibiotic-resistant Staphylococcus aureus.
abstract: Adaptations that enable antimicrobial resistance often pose a fitness cost to the microorganism. Resistant pathogens must therefore overcome such fitness decreases to persist within their hosts. Here we demonstrate that the reduced fitness associated with one resistance-conferring mutation can be offset by community interactions with microorganisms harboring alternative mutations or via interactions with the human microbiota. Mutations that confer antibiotic resistance in the human pathogen Staphylococcus aureus led to decreased fitness, whereas coculture or coinfection of two distinct mutants resulted in collective recovery of fitness comparable to that of wild-type. Such fitness enhancements result from the exchange of metabolites between distinct mutants, leading to enhanced growth, virulence factor production, and pathogenicity. Interspecies fitness enhancements were also identified, as members of the human microbiota can promote growth of antibiotic-resistant S. aureus. Thus, inter- and intraspecies community interactions offset fitness costs and enable S. aureus to develop antibiotic resistance without loss of virulence.
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, 1161 21(st) Avenue South, Nashville, TN 37232, USA.
authors.forename: Neal D
authors.initials: ND
authors.lastname: Hammer
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, 1161 21(st) Avenue South, Nashville, TN 37232, USA; Department of Pediatrics, Division of Pediatric Infectious Diseases, Vanderbilt University School of Medicine, 1161 21(st) Avenue South, Nashville, TN 37232, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Cassat
authors.affiliation: Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University School of Medicine, 1161 21(st) Avenue South Nashville, TN 37232, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Noto
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, 1161 21(st) Avenue South, Nashville, TN 37232, USA.
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Lojek
authors.affiliation: Department of Pediatrics, Division of Allergy, Immunology, and Pulmonary Medicine, Vanderbilt University School of Medicine, 1161 21(st) Avenue South, Nashville, TN 37232, USA.
authors.forename: Ashley D
authors.initials: AD
authors.lastname: Chadha
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, 1161 21(st) Avenue South, Nashville, TN 37232, USA.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Schmitz
authors.affiliation: Department of Pediatrics, Division of Pediatric Infectious Diseases, Vanderbilt University School of Medicine, 1161 21(st) Avenue South, Nashville, TN 37232, USA.
authors.forename: C Buddy
authors.initials: CB
authors.lastname: Creech
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, 1161 21(st) Avenue South, Nashville, TN 37232, USA. Electronic address: eric.skaar@vanderbilt.edu.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Skaar
mesh_terms: D000818:Animals; D060085:Coinfection / Q000382:microbiology / Q000473:pathology; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial; D006801:Humans; D008810:Mice, Inbred C57BL; D056265:Microbial Interactions; D009154:Mutation; D010019:Osteomyelitis / Q000382:microbiology / Q000473:pathology; D013203:Staphylococcal Infections / Q000382:microbiology / Q000473:pathology; D013211:Staphylococcus aureus / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D014774:Virulence