OmpR-dependent and OmpR-independent responses of Escherichia coli to sublethal attack by the neutrophil bactericidal/permeability increasing protein.
Bactericidal/permeability-increasing protein (BPI) of neutrophils is a lipopolysaccharide (LPS)-binding antibacterial protein with specificity for Gram negative bacteria. BPI binding to the bacterial surface rapidly triggers potentially reversible bacterial growth inhibition and alterations of the outer membrane and, later, disruption of the inner membrane and lethal injury. Initial effects include selective OmpR-dependent changes in the synthesis of outer membrane porins (OmpF and OmpC). Because OmpR is a global transcriptional regulator, we have examined its possible role in responses of E. coli to sublethal injury caused by BPI. Early (<15 min) reversible effects of BPI on bacterial colony-forming ability and outer membrane permeability were virtually identical in isogenic wild-type (wt) and ompR- E. coli. Both strains could repair the outer membrane permeability barrier after Mg2+-induced displacement of bound BPI. However, OmpR was essential for the ability of E. coli to tolerate low doses of BPI and escape the progression of sublethal to lethal damage. Scanning electron microscopy revealed that BPI treatment produced greater membrane perturbations in the ompR- strain, apparent even before lethal injury. These findings suggest that the fate of E. coli exposed to BPI depends on both OmpR-independent mechanisms engaged in outer membrane repair and OmpR- dependent processes that modulate porin synthesis and retard progression of injury from the outer to the inner membrane.
Prohinar
Polonca
P
Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA.
Forst
Steve A
SA
Reed
Deoine
D
Mandic-Mulec
Ines
I
Weiss
Jerrold
J
D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; D001798:Blood Proteins / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008565:Membrane Proteins; D008855:Microscopy, Electron, Scanning; D009504:Neutrophils / Q000276:immunology; D018272:Porins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; D001798:Blood Proteins; D008565:Membrane Proteins; C113724:OmpC protein; C109237:OmpF protein; D018272:Porins; D015534:Trans-Activators; C021623:bactericidal permeability increasing protein; C112177:osmolarity response regulator proteins