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Delineating the Role of the msaABCR Operon in Staphylococcal Overflow Metabolism

Staphylococcus aureus is an important human pathogen that can infect almost every organ system, resulting in a high incidence of morbidity and mortality. The msaABCR operon is an important regulator of several staphylococcal phenotypes, including biofilm development, cell wall crosslinking, antibiot...

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Autores principales: G C, Bibek, Sahukhal, Gyan S., Elasri, Mohamed O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204165/
https://www.ncbi.nlm.nih.gov/pubmed/35722290
http://dx.doi.org/10.3389/fmicb.2022.914512
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author G C, Bibek
Sahukhal, Gyan S.
Elasri, Mohamed O.
author_facet G C, Bibek
Sahukhal, Gyan S.
Elasri, Mohamed O.
author_sort G C, Bibek
collection PubMed
description Staphylococcus aureus is an important human pathogen that can infect almost every organ system, resulting in a high incidence of morbidity and mortality. The msaABCR operon is an important regulator of several staphylococcal phenotypes, including biofilm development, cell wall crosslinking, antibiotic resistance, oxidative stress, and acute and chronic implant-associated osteomyelitis. Our previous study showed that, by modulating murein hydrolase activity, the msaABCR operon negatively regulates the proteases that govern cell death. Here, we report further elucidation of the mechanism of cell death, which is regulated by the msaABCR operon at the molecular level in the USA300 LAC strain. We showed that deletion of msaABCR enhances weak-acid-dependent cell death, because, in the biofilm microenvironment, this mutant strain consumes glucose and produces acetate and acetoin at higher rates than wild-type USA300 LAC strain. We proposed the increased intracellular acidification leads to increased cell death. MsaB, a dual-function transcription factor and RNA chaperone, is a negative regulator of the cidR regulon, which has been shown to play an important role in overflow metabolism and programmed cell death during biofilm development in S. aureus. We found that MsaB binds directly to the cidR promoter, which represses expression of the cidR regulon and prevents transcription of the cidABC and alsSD operons. In addition, we observed that pyruvate induced expression of the msaABCR operon (MsaB). The results reported here have enabled us to decipher the role of the msaABCR operon in staphylococcal metabolic adaption during biofilm development.
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spelling pubmed-92041652022-06-18 Delineating the Role of the msaABCR Operon in Staphylococcal Overflow Metabolism G C, Bibek Sahukhal, Gyan S. Elasri, Mohamed O. Front Microbiol Microbiology Staphylococcus aureus is an important human pathogen that can infect almost every organ system, resulting in a high incidence of morbidity and mortality. The msaABCR operon is an important regulator of several staphylococcal phenotypes, including biofilm development, cell wall crosslinking, antibiotic resistance, oxidative stress, and acute and chronic implant-associated osteomyelitis. Our previous study showed that, by modulating murein hydrolase activity, the msaABCR operon negatively regulates the proteases that govern cell death. Here, we report further elucidation of the mechanism of cell death, which is regulated by the msaABCR operon at the molecular level in the USA300 LAC strain. We showed that deletion of msaABCR enhances weak-acid-dependent cell death, because, in the biofilm microenvironment, this mutant strain consumes glucose and produces acetate and acetoin at higher rates than wild-type USA300 LAC strain. We proposed the increased intracellular acidification leads to increased cell death. MsaB, a dual-function transcription factor and RNA chaperone, is a negative regulator of the cidR regulon, which has been shown to play an important role in overflow metabolism and programmed cell death during biofilm development in S. aureus. We found that MsaB binds directly to the cidR promoter, which represses expression of the cidR regulon and prevents transcription of the cidABC and alsSD operons. In addition, we observed that pyruvate induced expression of the msaABCR operon (MsaB). The results reported here have enabled us to decipher the role of the msaABCR operon in staphylococcal metabolic adaption during biofilm development. Frontiers Media S.A. 2022-06-03 /pmc/articles/PMC9204165/ /pubmed/35722290 http://dx.doi.org/10.3389/fmicb.2022.914512 Text en Copyright © 2022 G C, Sahukhal and Elasri. 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
G C, Bibek
Sahukhal, Gyan S.
Elasri, Mohamed O.
Delineating the Role of the msaABCR Operon in Staphylococcal Overflow Metabolism
title Delineating the Role of the msaABCR Operon in Staphylococcal Overflow Metabolism
title_full Delineating the Role of the msaABCR Operon in Staphylococcal Overflow Metabolism
title_fullStr Delineating the Role of the msaABCR Operon in Staphylococcal Overflow Metabolism
title_full_unstemmed Delineating the Role of the msaABCR Operon in Staphylococcal Overflow Metabolism
title_short Delineating the Role of the msaABCR Operon in Staphylococcal Overflow Metabolism
title_sort delineating the role of the msaabcr operon in staphylococcal overflow metabolism
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204165/
https://www.ncbi.nlm.nih.gov/pubmed/35722290
http://dx.doi.org/10.3389/fmicb.2022.914512
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