Abstract |
Upon ingestion of contaminated food, Listeria monocytogenes can cause serious infections in humans that are normally treated with β- lactam antibiotics. These target Listeria'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 A1 and PBP A2 have transglycosylase and transpeptidase domains catalyzing glycan chain polymerization and peptide cross-linking, respectively, whereas the three class B HMW PBPs B1, B2 and B3 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 A1 and PBP A2 could not be inactivated simultaneously, and a conditional double mutant strain is largely inducer dependent. PBP B1 is required for rod-shape and PBP B2 for cross-wall biosynthesis and viability, whereas PBP B3 is dispensable for growth and cell division. PBP B1 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.
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Authors | Jeanine Rismondo, Lars Möller, Christine Aldridge, Joe Gray, Waldemar Vollmer, Sven Halbedel |
Journal | Molecular microbiology
(Mol Microbiol)
Vol. 95
Issue 2
Pg. 332-51
(Jan 2015)
ISSN: 1365-2958 [Electronic] England |
PMID | 25424554
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2014 John Wiley & Sons Ltd. |
Chemical References |
- Anti-Bacterial Agents
- Bacterial Proteins
- Penicillin-Binding Proteins
- Peptidoglycan
- beta-Lactams
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Topics |
- 3T3 Cells
- Animals
- Anti-Bacterial Agents
(pharmacology)
- Bacterial Proteins
(metabolism)
- Cell Wall
(chemistry, physiology)
- HeLa Cells
- Humans
- Listeria monocytogenes
(cytology, drug effects, pathogenicity, physiology)
- Mice
- Microbial Sensitivity Tests
- Mutation
- Penicillin-Binding Proteins
(genetics, metabolism)
- Peptidoglycan
(metabolism)
- Virulence
(genetics)
- beta-Lactams
(pharmacology)
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