Cargando…

Dissecting the roles of peptidoglycan synthetic and autolytic activities in the walled to L-form bacterial transition

Bacterial cells are surrounded by a peptidoglycan (PG) wall, which is a crucial target for antibiotics. It is well known that treatment with cell wall-active antibiotics occasionally converts bacteria to a non-walled “L-form” state that requires the loss of cell wall integrity. L-forms may have an i...

Descripción completa

Detalles Bibliográficos
Autores principales: Kawai, Yoshikazu, Errington, Jeff
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10272550/
https://www.ncbi.nlm.nih.gov/pubmed/37333659
http://dx.doi.org/10.3389/fmicb.2023.1204979
_version_ 1785059520665354240
author Kawai, Yoshikazu
Errington, Jeff
author_facet Kawai, Yoshikazu
Errington, Jeff
author_sort Kawai, Yoshikazu
collection PubMed
description Bacterial cells are surrounded by a peptidoglycan (PG) wall, which is a crucial target for antibiotics. It is well known that treatment with cell wall-active antibiotics occasionally converts bacteria to a non-walled “L-form” state that requires the loss of cell wall integrity. L-forms may have an important role in antibiotic resistance and recurrent infection. Recent work has revealed that inhibition of de novo PG precursor synthesis efficiently induces the L-form conversion in a wide range of bacteria, but the molecular mechanisms remain poorly understood. Growth of walled bacteria requires the orderly expansion of the PG layer, which involves the concerted action not just of synthases but also degradative enzymes called autolysins. Most rod-shaped bacteria have two complementary systems for PG insertion, the Rod and aPBP systems. Bacillus subtilis has two major autolysins, called LytE and CwlO, which are thought to have partially redundant functions. We have dissected the functions of autolysins, relative to the Rod and aPBP systems, during the switch to L-form state. Our results suggest that when de novo PG precursor synthesis is inhibited, residual PG synthesis occurs specifically via the aPBP pathway, and that this is required for continued autolytic activity by LytE/CwlO, resulting in cell bulging and efficient L-form emergence. The failure of L-form generation in cells lacking aPBPs was rescued by enhancing the Rod system and in this case, emergence specifically required LytE but was not associated with cell bulging. Our results suggest that two distinct pathways of L-form emergence exist depending on whether PG synthesis is being supported by the aPBP or RodA PG synthases. This work provides new insights into mechanisms of L-form generation, and specialisation in the roles of essential autolysins in relation to the recently recognised dual PG synthetic systems of bacteria.
format Online
Article
Text
id pubmed-10272550
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-102725502023-06-17 Dissecting the roles of peptidoglycan synthetic and autolytic activities in the walled to L-form bacterial transition Kawai, Yoshikazu Errington, Jeff Front Microbiol Microbiology Bacterial cells are surrounded by a peptidoglycan (PG) wall, which is a crucial target for antibiotics. It is well known that treatment with cell wall-active antibiotics occasionally converts bacteria to a non-walled “L-form” state that requires the loss of cell wall integrity. L-forms may have an important role in antibiotic resistance and recurrent infection. Recent work has revealed that inhibition of de novo PG precursor synthesis efficiently induces the L-form conversion in a wide range of bacteria, but the molecular mechanisms remain poorly understood. Growth of walled bacteria requires the orderly expansion of the PG layer, which involves the concerted action not just of synthases but also degradative enzymes called autolysins. Most rod-shaped bacteria have two complementary systems for PG insertion, the Rod and aPBP systems. Bacillus subtilis has two major autolysins, called LytE and CwlO, which are thought to have partially redundant functions. We have dissected the functions of autolysins, relative to the Rod and aPBP systems, during the switch to L-form state. Our results suggest that when de novo PG precursor synthesis is inhibited, residual PG synthesis occurs specifically via the aPBP pathway, and that this is required for continued autolytic activity by LytE/CwlO, resulting in cell bulging and efficient L-form emergence. The failure of L-form generation in cells lacking aPBPs was rescued by enhancing the Rod system and in this case, emergence specifically required LytE but was not associated with cell bulging. Our results suggest that two distinct pathways of L-form emergence exist depending on whether PG synthesis is being supported by the aPBP or RodA PG synthases. This work provides new insights into mechanisms of L-form generation, and specialisation in the roles of essential autolysins in relation to the recently recognised dual PG synthetic systems of bacteria. Frontiers Media S.A. 2023-06-02 /pmc/articles/PMC10272550/ /pubmed/37333659 http://dx.doi.org/10.3389/fmicb.2023.1204979 Text en Copyright © 2023 Kawai and Errington. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Kawai, Yoshikazu
Errington, Jeff
Dissecting the roles of peptidoglycan synthetic and autolytic activities in the walled to L-form bacterial transition
title Dissecting the roles of peptidoglycan synthetic and autolytic activities in the walled to L-form bacterial transition
title_full Dissecting the roles of peptidoglycan synthetic and autolytic activities in the walled to L-form bacterial transition
title_fullStr Dissecting the roles of peptidoglycan synthetic and autolytic activities in the walled to L-form bacterial transition
title_full_unstemmed Dissecting the roles of peptidoglycan synthetic and autolytic activities in the walled to L-form bacterial transition
title_short Dissecting the roles of peptidoglycan synthetic and autolytic activities in the walled to L-form bacterial transition
title_sort dissecting the roles of peptidoglycan synthetic and autolytic activities in the walled to l-form bacterial transition
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10272550/
https://www.ncbi.nlm.nih.gov/pubmed/37333659
http://dx.doi.org/10.3389/fmicb.2023.1204979
work_keys_str_mv AT kawaiyoshikazu dissectingtherolesofpeptidoglycansyntheticandautolyticactivitiesinthewalledtolformbacterialtransition
AT erringtonjeff dissectingtherolesofpeptidoglycansyntheticandautolyticactivitiesinthewalledtolformbacterialtransition