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 PSM␣1 and PSM␣2. Notably, processed PSM␣1 and PSM␣2 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.

Novel Phenol-soluble Modulin Derivatives in Community-associated Methicillin-resistant Staphylococcus aureus Identified through Imaging Mass Spectrometry

“…Antimicrobial Activity of PSM Derivatives-Otto and colleagues (11) suggested that PSM derivatives might serve antimicrobial functions relevant for CA-MRSA niche establishment. To this end, we set up S. aureus bacterial-bacterial interactions, first with the common skin microbe S. epidermidis and second with a leading human skin pathogen, GAS.…”

“…More recently, the same investigators determined the existence of truncated forms of PSMs with antimicrobial activity against other Gram-positive bacteria. It was proposed that the truncated PSMs contribute to CA-MRSA niche establishment by providing a competitive advantage over other microflora, thereby allowing skin colonization, which predisposes to subsequent soft tissue infection (11).…”

Staphylococcus aureus toxins – Their functions and genetics

“…proteolytically processed PSMα1 and PSMα2 peptides show antimicrobial activity and 31 interfere with competing colonizing pathogens (Joo, Cheung et al 2011). Finally, they 32 appear to contribute to the structuring of biofilms during S. aureus infection (Periasamy, (Periasamy, Chatterjee et al 2012).…”

The AgrD N-Terminal Leader Peptide of Staphylococcus aureus Has Cytolytic and Amyloidogenic Properties

“…PSMs are of particular interest because they perform multiple roles in pathogenesis. These short peptides compound pathogenicity by activating host receptor-mediated inflammatory responses (12)(13)(14)(15)(16)(17), lysing red and white blood cells (16,18,19), altering biofilm development (20)(21)(22)(23), and acting as antimicrobial agents against nicheoccupying organisms in the host (24)(25)(26)(27).…”