Inactivation of Escherichia coli penicillin-binding proteins by human neutrophils.
Neutrophils use a variety of microbicidal mechanisms in their role as one of the primary arms of the human host defense system. We have previously observed that a cell-free system containing myeloperoxidase (MPO), one of the major components of the neutrophil's oxidative antimicrobial systems, inactivated microbial penicillin-binding proteins (PBPs), which mediate the formation of the peptidoglycan layer of eubacterial cell walls. This is a potentially important mechanism of MPO-mediated bacterial toxicity. Since numerous other microbicidal systems, both oxidative and nonoxidative, are used by whole neutrophils, we investigated the effect of intact neutrophils on Escherichia coli PBPs. Penicillin binding activity was progressively reduced by neutrophil exposure for all PBPs. Loss of penicillin binding activity correlated well with loss of microbial viability for almost all PBPs. Azide-treated neutrophils, MPO-deficient neutrophils, and chronic granulomatous disease neutrophils inactivated E. coli PBPs in a manner similar to that of normal neutrophils, suggesting that MPO-independent, and even oxygen-independent, microbicidal systems are also involved in inactivation of PBPs. PBP inactivation, an antimicrobial strategy used by beta-lactam-producing molds (and now by physicians), may be an important microbicidal mechanism used by human neutrophils.
Rakita
R M
RM
Department of Internal Medicine, University of Texas Medical School, Houston.
Michel
B R
BR
Rosen
H
H
D001386:Azides / Q000494:pharmacology; D001426:Bacterial Proteins; D001770:Blood Bactericidal Activity; D002352:Carrier Proteins / Q000378:metabolism*; D004926:Escherichia coli / Q000737:chemistry; D006105:Granulomatous Disease, Chronic / Q000378:metabolism; D006602:Hexosyltransferases; D006801:Humans; D066298:In Vitro Techniques; D002267:Muramoylpentapeptide Carboxypeptidase / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D009195:Peroxidase / Q000378:metabolism
D001386:Azides; D001426:Bacterial Proteins; D002352:Carrier Proteins; D046915:Penicillin-Binding Proteins; D009195:Peroxidase; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase