AUTHOR=Ramsey Matthew M. , Freire Marcelo O. , Gabrilska Rebecca A. , Rumbaugh Kendra P. , Lemon Katherine P. 

TITLE=Staphylococcus aureus Shifts toward Commensalism in Response to Corynebacterium Species

JOURNAL=Frontiers in Microbiology

VOLUME=7

YEAR=2016

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2016.01230

DOI=10.3389/fmicb.2016.01230

ISSN=1664-302X

ABSTRACT=<p><italic>Staphylococcus aureus</italic>–human interactions result in a continuum of outcomes from commensalism to pathogenesis. <italic>S. aureus</italic> is a clinically important pathogen that asymptomatically colonizes ~25% of humans as a member of the nostril and skin microbiota, where it resides with other bacteria including commensal <italic>Corynebacterium</italic> species. Commensal <italic>Corynebacterium</italic> spp. are also positively correlated with <italic>S. aureus</italic> in chronic polymicrobial diabetic foot infections, distinct from acute monomicrobial <italic>S. aureus</italic> infections. Recent work by our lab and others indicates that microbe–microbe interactions between <italic>S. aureus</italic> and human skin/nasal commensals, including <italic>Corynebacterium</italic> species, affect <italic>S. aureus</italic> behavior and fitness. Thus, we hypothesized that <italic>S. aureus</italic> interactions with <italic>Corynebacterium</italic> spp. diminish <italic>S. aureus</italic> virulence. We tested this by assaying for changes in <italic>S. aureus</italic> gene expression during <italic>in vitro</italic> mono- versus coculture with <italic>Corynebacterium striatum</italic>, a common skin and nasal commensal. We observed a broad shift in <italic>S. aureus</italic> gene transcription during <italic>in vitro</italic> growth with <italic>C. striatum</italic>, including increased transcription of genes known to exhibit increased expression during human nasal colonization and decreased transcription of virulence genes. <italic>S. aureus</italic> uses several regulatory pathways to transition between commensal and pathogenic states. One of these, the quorum signal accessory gene regulator (<italic>agr</italic>) system, was strongly inhibited in response to <italic>Corynebacterium</italic> spp. Phenotypically, <italic>S. aureus</italic> exposed to <italic>C. striatum</italic> exhibited increased adhesion to epithelial cells, reflecting a commensal state, and decreased hemolysin activity, reflecting an attenuation of virulence. Consistent with this, <italic>S. aureus</italic> displayed diminished fitness in experimental <italic>in vivo</italic> coinfection with <italic>C. striatum</italic> when compared to monoinfection. These data support a model in which <italic>S. aureus</italic> shifts from virulence toward a commensal state when exposed to commensal <italic>Corynebacterium</italic> species.</p>