Effect of D-alanylation of (lipo)teichoic acids of Staphylococcus aureus on host secretory phospholipase A2 action before and after phagocytosis by human neutrophils.
Invading bacteria such as Staphylococcus aureus induce mobilization of professional phagocytes (e.g., neutrophils) and extracellular antibacterial proteins (e.g., group IIA phospholipase A2 (gIIA PLA2)). Accumulation of gIIA PLA2 in inflammatory fluids confers potent extracellular antistaphylococcal activity and at lower concentrations promotes bacterial phospholipid degradation during phagocytosis of S. aureus by human neutrophils. D-alanylation of (lipo) teichoic acids of S. aureus increases bacterial resistance to gIIA PLA2 approximately 100-fold, raising the possibility that the resistance of ingested S. aureus to related gV and gX secretory PLA2 present in human neutrophil granules depends on D-alanylation mediated by the dlt operon. However, we show that isogenic wild-type and dltA S. aureus are equally resistant to gV/X PLA2 during phagocytosis and when exposed to the purified enzymes. The fates of wild-type and dltA S. aureus exposed to serum and human neutrophils differed significantly only when extracellular gIIA PLA2 was also present before phagocytosis. The extreme potency of the gIIA PLA2 toward dltA S. aureus suggests that even small amounts of this extracellular enzyme mobilized early in inflammation could contribute substantially to the overall cytotoxicity of acute inflammatory exudates toward S. aureus when D-alanylation of (lipo)teichoic acids is limiting.
Hunt
Catherine L
CL
The Inflammation Program, University of Iowa and Veterans Affairs Medical Center, Iowa City 52242, USA.
Nauseef
William M
WM
Weiss
Jerrold P
JP
D000409:Alanine / Q000737:chemistry; D006801:Humans; D007113:Immunity, Innate; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000737:chemistry / Q000378:metabolism*; D009504:Neutrophils / Q000201:enzymology* / Q000276:immunology* / Q000382:microbiology; D010741:Phospholipases A / Q000145:classification / Q000276:immunology / Q000378:metabolism*; D054467:Phospholipases A2; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology* / Q000378:metabolism*; D013682:Teichoic Acids / Q000737:chemistry / Q000378:metabolism*
D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D013682:Teichoic Acids; C009900:lipoteichoic acid; D010741:Phospholipases A; D054467:Phospholipases A2; D000409:Alanine