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A Decrease in Fatty Acid Synthesis Rescues Cells with Limited Peptidoglycan Synthesis Capacity

Proper synthesis and maintenance of a multilayered cell envelope are critical for bacterial fitness. However, whether mechanisms exist to coordinate synthesis of the membrane and peptidoglycan layers is unclear. In Bacillus subtilis, synthesis of peptidoglycan (PG) during cell elongation is mediated...

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Detalles Bibliográficos
Autores principales: Willdigg, Jessica R., Patel, Yesha, Helmann, John D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10128001/
https://www.ncbi.nlm.nih.gov/pubmed/37017514
http://dx.doi.org/10.1128/mbio.00475-23
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author Willdigg, Jessica R.
Patel, Yesha
Helmann, John D.
author_facet Willdigg, Jessica R.
Patel, Yesha
Helmann, John D.
author_sort Willdigg, Jessica R.
collection PubMed
description Proper synthesis and maintenance of a multilayered cell envelope are critical for bacterial fitness. However, whether mechanisms exist to coordinate synthesis of the membrane and peptidoglycan layers is unclear. In Bacillus subtilis, synthesis of peptidoglycan (PG) during cell elongation is mediated by an elongasome complex acting in concert with class A penicillin-binding proteins (aPBPs). We previously described mutant strains limited in their capacity for PG synthesis due to a loss of aPBPs and an inability to compensate by upregulation of elongasome function. Growth of these PG-limited cells can be restored by suppressor mutations predicted to decrease membrane synthesis. One suppressor mutation leads to an altered function repressor, FapR*, that functions as a super-repressor and leads to decreased transcription of fatty acid synthesis (FAS) genes. Consistent with fatty acid limitation mitigating cell wall synthesis defects, inhibition of FAS by cerulenin also restored growth of PG-limited cells. Moreover, cerulenin can counteract the inhibitory effect of β-lactams in some strains. These results imply that limiting PG synthesis results in impaired growth, in part, due to an imbalance of PG and cell membrane synthesis and that B. subtilis lacks a robust physiological mechanism to reduce membrane synthesis when PG synthesis is impaired.
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spelling pubmed-101280012023-04-26 A Decrease in Fatty Acid Synthesis Rescues Cells with Limited Peptidoglycan Synthesis Capacity Willdigg, Jessica R. Patel, Yesha Helmann, John D. mBio Research Article Proper synthesis and maintenance of a multilayered cell envelope are critical for bacterial fitness. However, whether mechanisms exist to coordinate synthesis of the membrane and peptidoglycan layers is unclear. In Bacillus subtilis, synthesis of peptidoglycan (PG) during cell elongation is mediated by an elongasome complex acting in concert with class A penicillin-binding proteins (aPBPs). We previously described mutant strains limited in their capacity for PG synthesis due to a loss of aPBPs and an inability to compensate by upregulation of elongasome function. Growth of these PG-limited cells can be restored by suppressor mutations predicted to decrease membrane synthesis. One suppressor mutation leads to an altered function repressor, FapR*, that functions as a super-repressor and leads to decreased transcription of fatty acid synthesis (FAS) genes. Consistent with fatty acid limitation mitigating cell wall synthesis defects, inhibition of FAS by cerulenin also restored growth of PG-limited cells. Moreover, cerulenin can counteract the inhibitory effect of β-lactams in some strains. These results imply that limiting PG synthesis results in impaired growth, in part, due to an imbalance of PG and cell membrane synthesis and that B. subtilis lacks a robust physiological mechanism to reduce membrane synthesis when PG synthesis is impaired. American Society for Microbiology 2023-04-05 /pmc/articles/PMC10128001/ /pubmed/37017514 http://dx.doi.org/10.1128/mbio.00475-23 Text en Copyright © 2023 Willdigg et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Willdigg, Jessica R.
Patel, Yesha
Helmann, John D.
A Decrease in Fatty Acid Synthesis Rescues Cells with Limited Peptidoglycan Synthesis Capacity
title A Decrease in Fatty Acid Synthesis Rescues Cells with Limited Peptidoglycan Synthesis Capacity
title_full A Decrease in Fatty Acid Synthesis Rescues Cells with Limited Peptidoglycan Synthesis Capacity
title_fullStr A Decrease in Fatty Acid Synthesis Rescues Cells with Limited Peptidoglycan Synthesis Capacity
title_full_unstemmed A Decrease in Fatty Acid Synthesis Rescues Cells with Limited Peptidoglycan Synthesis Capacity
title_short A Decrease in Fatty Acid Synthesis Rescues Cells with Limited Peptidoglycan Synthesis Capacity
title_sort decrease in fatty acid synthesis rescues cells with limited peptidoglycan synthesis capacity
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10128001/
https://www.ncbi.nlm.nih.gov/pubmed/37017514
http://dx.doi.org/10.1128/mbio.00475-23
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