Loss of elongation factor P disrupts bacterial outer membrane integrity

TY - JOUR

T1 - Loss of elongation factor P disrupts bacterial outer membrane integrity

AU - Zou, S Betty

AU - Hersch, Steven J

AU - Roy, Hervé

AU - Wiggers, J Brad

AU - Leung, Andrea S

AU - Buranyi, Stephen

AU - Xie, Jinglin Lucy

AU - Dare, Kiley

AU - Ibba, Michael

AU - Navarre, William Wiley

PY - 2012/1

Y1 - 2012/1

N2 - Elongation factor P (EF-P) is posttranslationally modified at a conserved lysyl residue by the coordinated action of two enzymes, PoxA and YjeK. We have previously established the importance of this modification in Salmonella stress resistance. Here we report that, like poxA and yjeK mutants, Salmonella strains lacking EF-P display increased susceptibility to hypoosmotic conditions, antibiotics, and detergents and enhanced resistance to the compound S-nitrosoglutathione. The susceptibility phenotypes are largely explained by the enhanced membrane permeability of the efp mutant, which exhibits increased uptake of the hydrophobic dye 1-N-phenylnaphthylamine (NPN). Analysis of the membrane proteomes of wild-type and efp mutant Salmonella strains reveals few changes, including the prominent overexpression of a single porin, KdgM, in the efp mutant outer membrane. Removal of KdgM in the efp mutant background ameliorates the detergent, antibiotic, and osmosensitivity phenotypes and restores wild-type permeability to NPN. Our data support a role for EF-P in the translational regulation of a limited number of proteins that, when perturbed, renders the cell susceptible to stress by the adventitious overexpression of an outer membrane porin.

AB - Elongation factor P (EF-P) is posttranslationally modified at a conserved lysyl residue by the coordinated action of two enzymes, PoxA and YjeK. We have previously established the importance of this modification in Salmonella stress resistance. Here we report that, like poxA and yjeK mutants, Salmonella strains lacking EF-P display increased susceptibility to hypoosmotic conditions, antibiotics, and detergents and enhanced resistance to the compound S-nitrosoglutathione. The susceptibility phenotypes are largely explained by the enhanced membrane permeability of the efp mutant, which exhibits increased uptake of the hydrophobic dye 1-N-phenylnaphthylamine (NPN). Analysis of the membrane proteomes of wild-type and efp mutant Salmonella strains reveals few changes, including the prominent overexpression of a single porin, KdgM, in the efp mutant outer membrane. Removal of KdgM in the efp mutant background ameliorates the detergent, antibiotic, and osmosensitivity phenotypes and restores wild-type permeability to NPN. Our data support a role for EF-P in the translational regulation of a limited number of proteins that, when perturbed, renders the cell susceptible to stress by the adventitious overexpression of an outer membrane porin.

KW - Anti-Bacterial Agents

KW - Bacterial Proteins

KW - Cell Membrane

KW - Detergents

KW - Drug Resistance, Bacterial

KW - Escherichia coli

KW - Gene Expression Regulation, Bacterial

KW - Mutation

KW - Osmolar Concentration

KW - Peptide Elongation Factors

KW - Permeability

KW - Plasmids

KW - Salmonella typhimurium

KW - Up-Regulation

U2 - 10.1128/JB.05864-11

DO - 10.1128/JB.05864-11

M3 - Journal article

C2 - 22081389

SN - 0021-9193

VL - 194

SP - 413

EP - 425

JO - Journal of Bacteriology

JF - Journal of Bacteriology

IS - 2

ER -