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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2023
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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. |
format | Online Article Text |
id | pubmed-10128001 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
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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