Inter- and Intraspecies Metabolite Exchange Promotes Virulence of Antibiotic-Resistant Staphylococcus aureus

• Published in: Cell host & microbe Vol. 16; no. 4; pp. 531 - 537
• Main Authors: Hammer, Neal D., Cassat, James E., Noto, Michael J., Lojek, Lisa J., Chadha, Ashley D., Schmitz, Jonathan E., Creech, C. Buddy, Skaar, Eric P.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.10.2014
• Subjects: Animals; Coinfection - microbiology; Coinfection - pathology; Disease Models, Animal; Drug Resistance, Bacterial; Humans; Mice, Inbred C57BL; Microbial Interactions; Mutation; Osteomyelitis - microbiology; Osteomyelitis - pathology; Staphylococcal Infections - microbiology; Staphylococcal Infections - pathology; Staphylococcus aureus - growth & development; Staphylococcus aureus - metabolism; Staphylococcus aureus - physiology; Virulence
• ISSN: 1931-3128; 1934-6069
• DOI: 10.1016/j.chom.2014.09.002

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. [Display omitted] •Coculture restores growth of fitness-impaired antibiotic-resistant S. aureus strains•Coinfection with antibiotic-resistant S. aureus strains results in enhanced virulence•Interspecies interactions also promote growth of antibiotic-resistant S. aureus•Growth and virulence enhancements require inter- and intraspecies metabolite exchange Staphylococcus aureus can exist as a respiration-deficient small colony variant (SCV) that is resistant to antimicrobials and causes persistent infections. Hammer et al. report that genetically distinct SCVs exchange metabolites between each other as well as members of the microbiome to increase the collective fitness of the staphylococcal population.