Two distinct penicillin binding proteins promote cell division in different Salmonella lifestyles

The bacterial cell wall preserves cell integrity in response to external insults and the internal turgor pressure. The major component of the cell wall is the peptidoglycan (PG); a giant macromolecule formed by glycan chains cross-linked by short peptides. The PG is synthesized by a stepwise process...

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Main Authors: Sónia Castanheira, Juan J. Cestero, Francisco García-del Portillo, M. Graciela Pucciarelli
Format: Article
Language:English
Published: Shared Science Publishers OG 2018-02-01
Series:Microbial Cell
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Online Access:http://microbialcell.com/researcharticles/two-distinct-penicillin-binding-proteins-promote-cell-division-in-different-salmonella-lifestyles/
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author Sónia Castanheira
Juan J. Cestero
Francisco García-del Portillo
M. Graciela Pucciarelli
author_facet Sónia Castanheira
Juan J. Cestero
Francisco García-del Portillo
M. Graciela Pucciarelli
author_sort Sónia Castanheira
collection DOAJ
description The bacterial cell wall preserves cell integrity in response to external insults and the internal turgor pressure. The major component of the cell wall is the peptidoglycan (PG); a giant macromolecule formed by glycan chains cross-linked by short peptides. The PG is synthesized by a stepwise process that includes cytosolic and periplasmic reactions. The building subunits -muropeptides- are incorporated into the growing macromolecule by transglycolyslation (TG) and transpeptidation (TP) reactions, which constitute the last biosynthetic steps. TP reactions, involving cleavage of the terminal D‑Ala-D-Ala bond in the stem peptide, are carried out by enzymes known generically as penicillin-binding proteins (PBPs) due to their capacity to bind β‑lactam antibiotics, which are D‑Ala-D-Ala structural analogues. On an average, bacterial genomes harbour a minimum of 10 PBP-encoding genes, most of them non-essential. This dispensability has led to the widely accepted concept of functional redundancy for many PBPs. An exemption is the PBP dedicated to build the septal PG required to separate daughter cells during cell division. To date, this division‑specific PBP was reported as unique in all known bacteria and, as a consequence, “essential”. Our recent results obtained in the intracellular bacterial pathogen Salmonella enterica serovar Typhimurium challenges this view since this bacterium has two PBPs that can independently build the division septum. One of these two division PG enzymes is orthologue of the division-specific PBP3 of Escherichia coli. The second enzyme, named PBP3SAL, is absent in non-pathogenic bacteria and, at least in S. Typhimurium, displays PG biosynthetic activity restricted to acidic conditions. Our work also revealed that it is possible to generate a S. Typhimurium mutant defective in PBP3, which cannot divide at neutral pH.
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spelling doaj-art-e039b008b3ff4e7cb5575622f669d3452025-08-20T02:52:37ZengShared Science Publishers OGMicrobial Cell2311-26382018-02-015316516810.15698/mic2018.03.622Two distinct penicillin binding proteins promote cell division in different Salmonella lifestylesSónia Castanheira0Juan J. Cestero1Francisco García-del Portillo2M. Graciela Pucciarelli3Laboratorio de Patógenos Bacterianos Intracelulares. Centro Nacional de Biotecnología-Consejo Superior de Investigaciones Científicas (CNB-CSIC), Madrid, Spain.Laboratorio de Patógenos Bacterianos Intracelulares. Centro Nacional de Biotecnología-Consejo Superior de Investigaciones Científicas (CNB-CSIC), Madrid, Spain.Laboratorio de Patógenos Bacterianos Intracelulares. Centro Nacional de Biotecnología-Consejo Superior de Investigaciones Científicas (CNB-CSIC), Madrid, Spain.Laboratorio de Patógenos Bacterianos Intracelulares. Centro Nacional de Biotecnología-Consejo Superior de Investigaciones Científicas (CNB-CSIC), Madrid, Spain.The bacterial cell wall preserves cell integrity in response to external insults and the internal turgor pressure. The major component of the cell wall is the peptidoglycan (PG); a giant macromolecule formed by glycan chains cross-linked by short peptides. The PG is synthesized by a stepwise process that includes cytosolic and periplasmic reactions. The building subunits -muropeptides- are incorporated into the growing macromolecule by transglycolyslation (TG) and transpeptidation (TP) reactions, which constitute the last biosynthetic steps. TP reactions, involving cleavage of the terminal D‑Ala-D-Ala bond in the stem peptide, are carried out by enzymes known generically as penicillin-binding proteins (PBPs) due to their capacity to bind β‑lactam antibiotics, which are D‑Ala-D-Ala structural analogues. On an average, bacterial genomes harbour a minimum of 10 PBP-encoding genes, most of them non-essential. This dispensability has led to the widely accepted concept of functional redundancy for many PBPs. An exemption is the PBP dedicated to build the septal PG required to separate daughter cells during cell division. To date, this division‑specific PBP was reported as unique in all known bacteria and, as a consequence, “essential”. Our recent results obtained in the intracellular bacterial pathogen Salmonella enterica serovar Typhimurium challenges this view since this bacterium has two PBPs that can independently build the division septum. One of these two division PG enzymes is orthologue of the division-specific PBP3 of Escherichia coli. The second enzyme, named PBP3SAL, is absent in non-pathogenic bacteria and, at least in S. Typhimurium, displays PG biosynthetic activity restricted to acidic conditions. Our work also revealed that it is possible to generate a S. Typhimurium mutant defective in PBP3, which cannot divide at neutral pH.http://microbialcell.com/researcharticles/two-distinct-penicillin-binding-proteins-promote-cell-division-in-different-salmonella-lifestyles/SalmonelladivisionPBP3PBP3SALacidic pHintracellularphagosome
spellingShingle Sónia Castanheira
Juan J. Cestero
Francisco García-del Portillo
M. Graciela Pucciarelli
Two distinct penicillin binding proteins promote cell division in different Salmonella lifestyles
Microbial Cell
Salmonella
division
PBP3
PBP3SAL
acidic pH
intracellular
phagosome
title Two distinct penicillin binding proteins promote cell division in different Salmonella lifestyles
title_full Two distinct penicillin binding proteins promote cell division in different Salmonella lifestyles
title_fullStr Two distinct penicillin binding proteins promote cell division in different Salmonella lifestyles
title_full_unstemmed Two distinct penicillin binding proteins promote cell division in different Salmonella lifestyles
title_short Two distinct penicillin binding proteins promote cell division in different Salmonella lifestyles
title_sort two distinct penicillin binding proteins promote cell division in different salmonella lifestyles
topic Salmonella
division
PBP3
PBP3SAL
acidic pH
intracellular
phagosome
url http://microbialcell.com/researcharticles/two-distinct-penicillin-binding-proteins-promote-cell-division-in-different-salmonella-lifestyles/
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AT juanjcestero twodistinctpenicillinbindingproteinspromotecelldivisionindifferentsalmonellalifestyles
AT franciscogarciadelportillo twodistinctpenicillinbindingproteinspromotecelldivisionindifferentsalmonellalifestyles
AT mgracielapucciarelli twodistinctpenicillinbindingproteinspromotecelldivisionindifferentsalmonellalifestyles