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Extensive re-modelling of the cell wall during the development of Staphylococcus aureus bacteraemia

The bloodstream represents a hostile environment that bacteria must overcome to cause bacteraemia. To understand how the major human pathogen Staphylococcus aureus manages this we have utilised a functional genomics approach to identify a number of new loci that affect the ability of the bacteria to...

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Autores principales: Douglas, Edward J.A., Palk, Nathanael, Brignoli, Tarcisio, Altwiley, Dina, Boura, Marcia, Laabei, Maisem, Recker, Mario, Cheung, Gordon Y.C., Liu, Ryan, Hsieh, Roger C., Otto, Michael, O’Brien, Eoin, McLoughlin, Rachel M., Massey, Ruth C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9980097/
https://www.ncbi.nlm.nih.gov/pubmed/36865143
http://dx.doi.org/10.1101/2023.02.23.529713
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author Douglas, Edward J.A.
Palk, Nathanael
Brignoli, Tarcisio
Altwiley, Dina
Boura, Marcia
Laabei, Maisem
Recker, Mario
Cheung, Gordon Y.C.
Liu, Ryan
Hsieh, Roger C.
Otto, Michael
O’Brien, Eoin
McLoughlin, Rachel M.
Massey, Ruth C.
author_facet Douglas, Edward J.A.
Palk, Nathanael
Brignoli, Tarcisio
Altwiley, Dina
Boura, Marcia
Laabei, Maisem
Recker, Mario
Cheung, Gordon Y.C.
Liu, Ryan
Hsieh, Roger C.
Otto, Michael
O’Brien, Eoin
McLoughlin, Rachel M.
Massey, Ruth C.
author_sort Douglas, Edward J.A.
collection PubMed
description The bloodstream represents a hostile environment that bacteria must overcome to cause bacteraemia. To understand how the major human pathogen Staphylococcus aureus manages this we have utilised a functional genomics approach to identify a number of new loci that affect the ability of the bacteria to survive exposure to serum, the critical first step in the development of bacteraemia. The expression of one of these genes, tcaA, was found to be induced upon exposure to serum, and we show that it is involved in the elaboration of a critical virulence factor, the wall teichoic acids (WTA), within the cell envelope. The activity of the TcaA protein alters the sensitivity of the bacteria to cell wall attacking agents, including antimicrobial peptides, human defence fatty acids, and several antibiotics. This protein also affects the autolytic activity and lysostaphin sensitivity of the bacteria, suggesting that in addition to changing WTA abundance in the cell envelope, it also plays a role in peptidoglycan crosslinking. With TcaA rendering the bacteria more susceptible to serum killing, while simultaneously increasing the abundance of WTA in the cell envelope, it was unclear what effect this protein may have during infection. To explore this, we examined human data and performed murine experimental infections. Collectively, our data suggests that whilst mutations in tcaA are selected for during bacteraemia, this protein positively contributes to the virulence of S. aureus through its involvement in altering the cell wall architecture of the bacteria, a process that appears to play a key role in the development of bacteraemia.
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spelling pubmed-99800972023-03-03 Extensive re-modelling of the cell wall during the development of Staphylococcus aureus bacteraemia Douglas, Edward J.A. Palk, Nathanael Brignoli, Tarcisio Altwiley, Dina Boura, Marcia Laabei, Maisem Recker, Mario Cheung, Gordon Y.C. Liu, Ryan Hsieh, Roger C. Otto, Michael O’Brien, Eoin McLoughlin, Rachel M. Massey, Ruth C. bioRxiv Article The bloodstream represents a hostile environment that bacteria must overcome to cause bacteraemia. To understand how the major human pathogen Staphylococcus aureus manages this we have utilised a functional genomics approach to identify a number of new loci that affect the ability of the bacteria to survive exposure to serum, the critical first step in the development of bacteraemia. The expression of one of these genes, tcaA, was found to be induced upon exposure to serum, and we show that it is involved in the elaboration of a critical virulence factor, the wall teichoic acids (WTA), within the cell envelope. The activity of the TcaA protein alters the sensitivity of the bacteria to cell wall attacking agents, including antimicrobial peptides, human defence fatty acids, and several antibiotics. This protein also affects the autolytic activity and lysostaphin sensitivity of the bacteria, suggesting that in addition to changing WTA abundance in the cell envelope, it also plays a role in peptidoglycan crosslinking. With TcaA rendering the bacteria more susceptible to serum killing, while simultaneously increasing the abundance of WTA in the cell envelope, it was unclear what effect this protein may have during infection. To explore this, we examined human data and performed murine experimental infections. Collectively, our data suggests that whilst mutations in tcaA are selected for during bacteraemia, this protein positively contributes to the virulence of S. aureus through its involvement in altering the cell wall architecture of the bacteria, a process that appears to play a key role in the development of bacteraemia. Cold Spring Harbor Laboratory 2023-04-24 /pmc/articles/PMC9980097/ /pubmed/36865143 http://dx.doi.org/10.1101/2023.02.23.529713 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Douglas, Edward J.A.
Palk, Nathanael
Brignoli, Tarcisio
Altwiley, Dina
Boura, Marcia
Laabei, Maisem
Recker, Mario
Cheung, Gordon Y.C.
Liu, Ryan
Hsieh, Roger C.
Otto, Michael
O’Brien, Eoin
McLoughlin, Rachel M.
Massey, Ruth C.
Extensive re-modelling of the cell wall during the development of Staphylococcus aureus bacteraemia
title Extensive re-modelling of the cell wall during the development of Staphylococcus aureus bacteraemia
title_full Extensive re-modelling of the cell wall during the development of Staphylococcus aureus bacteraemia
title_fullStr Extensive re-modelling of the cell wall during the development of Staphylococcus aureus bacteraemia
title_full_unstemmed Extensive re-modelling of the cell wall during the development of Staphylococcus aureus bacteraemia
title_short Extensive re-modelling of the cell wall during the development of Staphylococcus aureus bacteraemia
title_sort extensive re-modelling of the cell wall during the development of staphylococcus aureus bacteraemia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9980097/
https://www.ncbi.nlm.nih.gov/pubmed/36865143
http://dx.doi.org/10.1101/2023.02.23.529713
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