title: Antimicrobial activity of community-associated methicillin-resistant Staphylococcus aureus is caused by phenol-soluble modulin derivatives.
abstract: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) are causing an ongoing pandemic of mostly skin and soft tissue infections. The success of CA-MRSA as pathogens is due to a combination of antibiotic resistance with high virulence. In addition, it has been speculated that CA-MRSA strains such as the epidemic U.S. clone USA300 have increased capacity to colonize human epithelia, owing to bacteriocin-based bacterial interference. We here analyzed the molecular basis of antimicrobial activity detected in S. aureus strains, including those of the USA300 lineage. In contrast to a previous hypothesis, we found that this activity is not due to expression of a lantibiotic-type bacteriocin, but proteolytically processed derivatives of the phenol-soluble modulin (PSM) peptides PSMα1 and PSMα2. Notably, processed PSMα1 and PSMα2 exhibited considerable activity against Streptococcus pyogenes, indicating a role of PSMs in the interference of S. aureus strains with the competing colonizing pathogen. Furthermore, by offering a competitive advantage during colonization of the human body, the characteristically high production of PSMs in USA300 and other CA-MRSA strains may thus contribute not only to virulence but also the exceptional capacity of those strains to sustainably spread in the population, which so far has remained poorly understood.
authors.affiliation: Laboratory of Human Bacterial Pathogenesis, NIAID, The National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Hwang-Soo
authors.initials: HS
authors.lastname: Joo
authors.forename: Gordon Y C
authors.initials: GY
authors.lastname: Cheung
authors.forename: Michael
authors.initials: M
authors.lastname: Otto
mesh_terms: D000890:Anti-Infective Agents / Q000378:metabolism*; D003141:Communicable Diseases / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D006801:Humans; D016106:Methicillin Resistance / Q000502:physiology*; D058873:Pandemics; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D018461:Soft Tissue Infections / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D013045:Species Specificity; D013207:Staphylococcal Skin Infections / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism*; D014481:United States / Q000453:epidemiology
chemical_list: D000890:Anti-Infective Agents; D010455:Peptides