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Discrete and overlapping functions of peptidoglycan synthases in growth, cell division and virulence of L isteria monocytogenes
Author(s) -
Rismondo Jeanine,
Möller Lars,
Aldridge Christine,
Gray Joe,
Vollmer Waldemar,
Halbedel Sven
Publication year - 2015
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 - 10.1111/mmi.12873
Subject(s) - peptidoglycan , penicillin binding proteins , biology , virulence , cell wall , mutant , glycosyltransferase , biochemistry , cell division , microbiology and biotechnology , autolysis (biology) , escherichia coli , gene , enzyme , cell
Summary Upon ingestion of contaminated food, L isteria monocytogenes can cause serious infections in humans that are normally treated with β‐lactam antibiotics. These target L isteria's five high molecular weight penicillin‐binding proteins ( HMW PBPs ), which are required for peptidoglycan biosynthesis. The two bi‐functional class A HMW PBPs PBP A 1 and PBP A 2 have transglycosylase and transpeptidase domains catalyzing glycan chain polymerization and peptide cross‐linking, respectively, whereas the three class B HMW PBPs B 1, B 2 and B 3 are monofunctional transpeptidases. The precise roles of these PBPs in the cell cycle are unknown. Here we show that green fluorescent protein ( GFP)‐PBP fusions localized either at the septum, the lateral wall or both, suggesting distinct and overlapping functions. Genetic data confirmed this view: PBP A 1 and PBP A 2 could not be inactivated simultaneously, and a conditional double mutant strain is largely inducer dependent. PBP B 1 is required for rod‐shape and PBP B 2 for cross‐wall biosynthesis and viability, whereas PBP B 3 is dispensable for growth and cell division. PBP B 1 depletion dramatically increased β‐lactam susceptibilities and stimulated spontaneous autolysis but had no effect on peptidoglycan cross‐linkage. Our in vitro virulence assays indicated that the complete set of all HMW PBPs is required for maximal virulence.