Key role of poly-gamma-DL-glutamic acid in immune evasion and virulence of Staphylococcus epidermidis.
Coagulase-negative staphylococci, with the leading species Staphylococcus epidermidis, are the predominant cause of hospital-acquired infections. Treatment is especially difficult owing to biofilm formation and frequent antibiotic resistance. However, virulence mechanisms of these important opportunistic pathogens have remained poorly characterized. Here we demonstrate that S. epidermidis secretes poly-gamma-DL-glutamic acid (PGA) to facilitate growth and survival in the human host. Importantly, PGA efficiently sheltered S. epidermidis from key components of innate host defense, namely antimicrobial peptides and neutrophil phagocytosis, and was indispensable for persistence during device-related infection. Furthermore, PGA protected S. epidermidis from high salt concentration, a key feature of its natural environment, the human skin. Notably, PGA was synthesized by all tested strains of S. epidermidis and a series of closely related coagulase-negative staphylococci, most of which are opportunistic pathogens. Our study presents important novel biological functions for PGA and indicates that PGA represents an excellent target for therapeutic maneuvers aimed at treating disease caused by S. epidermidis and related staphylococci.
Kocianova
Stanislava
S
Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Hamilton, Montana 59840, USA.
Vuong
Cuong
C
Yao
Yufeng
Y
Voyich
Jovanka M
JM
Fischer
Elizabeth R
ER
DeLeo
Frank R
FR
Otto
Michael
M
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D002408:Catheters, Indwelling / Q000382:microbiology; D003428:Cross Infection / Q000276:immunology / Q000382:microbiology; D005798:Genes, Bacterial; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D010802:Phylogeny; D011099:Polyglutamic Acid / Q000378:metabolism*; D012492:Salts / Q000378:metabolism; D013203:Staphylococcal Infections / Q000276:immunology* / Q000382:microbiology; D013212:Staphylococcus epidermidis / Q000166:cytology / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*
D023181:Antimicrobial Cationic Peptides; D012492:Salts; D011099:Polyglutamic Acid