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Formate protects stationary‐phase Escherichia coli and Salmonella cells from killing by a cationic antimicrobial peptide
Author(s) -
Barker Helen C.,
Kinsella Niamh,
Jaspe Almudena,
Friedrich Thorsten,
O’Connor C. David
Publication year - 2000
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1046/j.1365-2958.2000.01820.x
Subject(s) - biology , rpos , formate dehydrogenase , escherichia coli , formate , biochemistry , antimicrobial , peptide , antimicrobial peptides , microbiology and biotechnology , salmonella , bacteria , gene expression , genetics , promoter , gene , catalysis
For a sustained infection, enteric bacterial pathogens must evade, resist or tolerate a variety of antimicrobial host defence peptides and proteins. We report here that specific organic acids protect stationary‐phase Escherichia coli and Salmonella cells from killing by a potent antimicrobial peptide derived from the human bactericidal/permeability‐increasing protein (BPI). BPI‐derived peptide P2 rapidly halted oxygen consumption by stationary‐phase cells preincubated with glucose, pyruvate or malate and caused a 10 9 ‐fold drop in cell viability within 90 min of addition. In marked contrast, O 2 consumption and viability were not significantly affected in stationary‐phase cells preincubated with formate or succinate. Experiments with fdhH, fdoG, fdnG, selC and sdhO mutants indicate that protection by formate and succinate requires their oxidation by the Fdh‐N formate dehydrogenase and succinate dehydrogenase respectively. Protection was also dependent on the BipA GTPase but did not require the RpoS sigma factor. We conclude that the primary lesion caused by this cationic peptide is not gross permeabilization of the bacterial cytoplasmic membrane but may involve specific disruption of the respiratory chain. Because P2 shares sequence similarity with a range of other antimicrobial peptides, its cytotoxic mechanism has broader significance. Additionally, protective quantities of formate are secreted by E. coli and Salmonella during growth suggesting that such compounds are important determinants of bacterial survival in the host.