Identification of novel cytolytic peptides as key virulence determinants for community-associated MRSA.
Methicillin-resistant Staphylococcus aureus (MRSA) remains a major human pathogen. Traditionally, MRSA infections occurred exclusively in hospitals and were limited to immunocompromised patients or individuals with predisposing risk factors. However, recently there has been an alarming epidemic caused by community-associated (CA)-MRSA strains, which can cause severe infections that can result in necrotizing fasciitis or even death in otherwise healthy adults outside of healthcare settings. In the US, CA-MRSA is now the cause of the majority of infections that result in trips to the emergency room. It is unclear what makes CA-MRSA strains more successful in causing human disease compared with their hospital-associated counterparts. Here we describe a class of secreted staphylococcal peptides that have a remarkable ability to recruit, activate and subsequently lyse human neutrophils, thus eliminating the main cellular defense against S. aureus infection. These peptides are produced at high concentrations by standard CA-MRSA strains and contribute significantly to the strains' ability to cause disease in animal models of infection. Our study reveals a previously uncharacterized set of S. aureus virulence factors that account at least in part for the enhanced virulence of CA-MRSA.
Wang
Rong
R
Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, 903 South 4th Street, Hamilton, Montana 59840, USA.
Braughton
Kevin R
KR
Kretschmer
Dorothee
D
Bach
Thanh-Huy L
TH
Queck
Shu Y
SY
Li
Min
M
Kennedy
Adam D
AD
Dorward
David W
DW
Klebanoff
Seymour J
SJ
Peschel
Andreas
A
DeLeo
Frank R
FR
Otto
Michael
M
D000818:Animals; D017714:Community-Acquired Infections / Q000209:etiology / Q000382:microbiology* / Q000473:pathology; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008712:Methicillin / Q000494:pharmacology*; D051379:Mice; D009504:Neutrophils / Q000382:microbiology; D010455:Peptides / Q000737:chemistry; D012867:Skin / Q000276:immunology; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000209:etiology / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000378:metabolism*; D014774:Virulence
D010455:Peptides; D008712:Methicillin