The MprF protein is required for lysinylation of phospholipids in listerial membranes and confers resistance to cationic antimicrobial peptides (CAMPs) on Listeria monocytogenes.
Pathogenic bacteria have to cope with defence mechanisms mediated by adaptive and innate immunity of the host cells. Cationic antimicrobial peptides (CAMPs) represent one of the most effective components of the host innate immune response. Here we establish the function of Lmo1695, a member of the VirR-dependent virulence regulon, recently identified in Listeria monocytogenes. Lmo1695 encodes a membrane protein of 98 kDa with strong homology to the multiple peptide resistance factor (MprF) of Staphylococcus aureus. Like staphylococcal MprF, we found that Lmo1695 is involved in the synthesis of the membrane phospholipid lysylphosphatidylglycerol (L-PG). In addition, Lmo1695 is also essential for lysinylation of diphosphatidylglycerol (DPG), another phospholipid widely distributed in bacterial membranes. A Deltalmo1695 mutant lacking the lysinylated phospholipids was particularly susceptible to CAMPs of human and bacterial origin. The mutant strain infected both epithelial cells and macrophages only poorly and was attenuated for virulence when tested in a mouse model of infection. Lmo1695 is a member of a growing list of survival factors which enable growth of L. monocytogenes in different environments.
Thedieck
Kathrin
K
Helmholtz Centre for Infection Research, Division of Cell and Immune Biology, Cellular Proteomics Group, Inhoffenstrasse 7, D-38124 Braunschweig, Germany.
Hain
Torsten
T
Mohamed
Walid
W
Tindall
Brian J
BJ
Nimtz
Manfred
M
Chakraborty
Trinad
T
Wehland
Jürgen
J
Jänsch
Lothar
L
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D024881:Drug Resistance, Bacterial; D008089:Listeria monocytogenes / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D008239:Lysine / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D010743:Phospholipids / Q000378:metabolism; D014774:Virulence / Q000235:genetics
D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; D010743:Phospholipids; D008239:Lysine