An exploration of mechanisms underlyingDesemzia incertacolonization resistance to methicillin-resistantStaphylococcus aureuson the skin

Abstract

ABSTRACTColonization of human skin and nares by methicillin-resistantStaphylococcus aureus(MRSA) leads to community spread of MRSA. This spread is exacerbated by transfer of MRSA between humans and livestock, particularly swine. Here we capitalized on the shared features between human and porcine skin, including shared MRSA colonization, to study novel bacterial mediators of MRSA colonization resistance. We focused on the poorly studied bacterial speciesDesemzia incerta, which we found to exert antimicrobial activity through a secreted product and exhibited colonization resistance against MRSA in anin vivomurine skin model. Using parallel genomic and biochemical investigation, we discovered thatD. incertasecretes an antimicrobial protein. Sequential protein purification and proteomics analysis identified 24 candidate inhibitory proteins, including a promising peptidoglycan hydrolase candidate. Aided by transcriptional analysis ofD. incertaand MRSA cocultures, we found that exposure toD. incertaleads to decreased MRSA biofilm production. These results emphasize the value in exploring microbial communities across a spectrum of hosts, which can lead to novel therapeutic agents as well as increased understanding of microbial competition.IMPORTANCEMethicillin-resistantStaphylococcus aureuscauses significant healthcare burden and can be spread to the human population via livestock transmission. Members of the skin microbiome can prevent MRSA colonization via a poorly-understood phenomenon known as colonization resistance. Here, we studied colonization resistance ofS. aureusby bacterial inhibitors previously identified from a porcine skin model. We identify a pig skin commensal,Desemzia incerta, that reduced MRSA colonization in a murine model. We employ a combination of genomic, proteomic, and transcriptomic analyses to explore the mechanisms of inhibition betweenD. incertaandS. aureus. We identify 24 candidate antimicrobial proteins secreted byD. incertathat could be responsible for its antimicrobial activity. We also find that exposure toD. incertaleads to decreasedS. aureusbiofilm formation. These findings show that the livestock transmission of MRSA can be exploited to uncover novel mechanisms of MRSA colonization resistance.