A combination of independent transcriptional regulators shapes bacterial virulence gene expression during infection.

Transcriptional regulatory networks are fundamental to how microbes alter gene expression in response to environmental stimuli, thereby playing a critical role in bacterial pathogenesis. However, understanding how bacterial transcriptional regulatory networks function during host-pathogen interactio...

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Autores principales:	Samuel A Shelburne, Randall J Olsen, Bryce Suber, Pranoti Sahasrabhojane, Paul Sumby, Richard G Brennan, James M Musser
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/65e56d1ce9b74353818fe78837283c29
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spelling	oai:doaj.org-article:65e56d1ce9b74353818fe78837283c292021-11-25T05:48:14ZA combination of independent transcriptional regulators shapes bacterial virulence gene expression during infection.1553-73661553-737410.1371/journal.ppat.1000817https://doaj.org/article/65e56d1ce9b74353818fe78837283c292010-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20333240/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Transcriptional regulatory networks are fundamental to how microbes alter gene expression in response to environmental stimuli, thereby playing a critical role in bacterial pathogenesis. However, understanding how bacterial transcriptional regulatory networks function during host-pathogen interaction is limited. Recent studies in group A Streptococcus (GAS) suggested that the transcriptional regulator catabolite control protein A (CcpA) influences many of the same genes as the control of virulence (CovRS) two-component gene regulatory system. To provide new information about the CcpA and CovRS networks, we compared the CcpA and CovR transcriptomes in a serotype M1 GAS strain. The transcript levels of several of the same genes encoding virulence factors and proteins involved in basic metabolic processes were affected in both DeltaccpA and DeltacovR isogenic mutant strains. Recombinant CcpA and CovR bound with high-affinity to the promoter regions of several co-regulated genes, including those encoding proteins involved in carbohydrate and amino acid metabolism. Compared to the wild-type parental strain, DeltaccpA and DeltacovRDeltaccpA isogenic mutant strains were significantly less virulent in a mouse myositis model. Inactivation of CcpA and CovR alone and in combination led to significant alterations in the transcript levels of several key GAS virulence factor encoding genes during infection. Importantly, the transcript level alterations in the DeltaccpA and DeltacovRDeltaccpA isogenic mutant strains observed during infection were distinct from those occurring during growth in laboratory medium. These data provide new knowledge regarding the molecular mechanisms by which pathogenic bacteria respond to environmental signals to regulate virulence factor production and basic metabolic processes during infection.Samuel A ShelburneRandall J OlsenBryce SuberPranoti SahasrabhojanePaul SumbyRichard G BrennanJames M MusserPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 6, Iss 3, p e1000817 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Samuel A Shelburne Randall J Olsen Bryce Suber Pranoti Sahasrabhojane Paul Sumby Richard G Brennan James M Musser A combination of independent transcriptional regulators shapes bacterial virulence gene expression during infection.
description	Transcriptional regulatory networks are fundamental to how microbes alter gene expression in response to environmental stimuli, thereby playing a critical role in bacterial pathogenesis. However, understanding how bacterial transcriptional regulatory networks function during host-pathogen interaction is limited. Recent studies in group A Streptococcus (GAS) suggested that the transcriptional regulator catabolite control protein A (CcpA) influences many of the same genes as the control of virulence (CovRS) two-component gene regulatory system. To provide new information about the CcpA and CovRS networks, we compared the CcpA and CovR transcriptomes in a serotype M1 GAS strain. The transcript levels of several of the same genes encoding virulence factors and proteins involved in basic metabolic processes were affected in both DeltaccpA and DeltacovR isogenic mutant strains. Recombinant CcpA and CovR bound with high-affinity to the promoter regions of several co-regulated genes, including those encoding proteins involved in carbohydrate and amino acid metabolism. Compared to the wild-type parental strain, DeltaccpA and DeltacovRDeltaccpA isogenic mutant strains were significantly less virulent in a mouse myositis model. Inactivation of CcpA and CovR alone and in combination led to significant alterations in the transcript levels of several key GAS virulence factor encoding genes during infection. Importantly, the transcript level alterations in the DeltaccpA and DeltacovRDeltaccpA isogenic mutant strains observed during infection were distinct from those occurring during growth in laboratory medium. These data provide new knowledge regarding the molecular mechanisms by which pathogenic bacteria respond to environmental signals to regulate virulence factor production and basic metabolic processes during infection.
format	article
author	Samuel A Shelburne Randall J Olsen Bryce Suber Pranoti Sahasrabhojane Paul Sumby Richard G Brennan James M Musser
author_facet	Samuel A Shelburne Randall J Olsen Bryce Suber Pranoti Sahasrabhojane Paul Sumby Richard G Brennan James M Musser
author_sort	Samuel A Shelburne
title	A combination of independent transcriptional regulators shapes bacterial virulence gene expression during infection.
title_short	A combination of independent transcriptional regulators shapes bacterial virulence gene expression during infection.
title_full	A combination of independent transcriptional regulators shapes bacterial virulence gene expression during infection.
title_fullStr	A combination of independent transcriptional regulators shapes bacterial virulence gene expression during infection.
title_full_unstemmed	A combination of independent transcriptional regulators shapes bacterial virulence gene expression during infection.
title_sort	combination of independent transcriptional regulators shapes bacterial virulence gene expression during infection.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/65e56d1ce9b74353818fe78837283c29
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A combination of independent transcriptional regulators shapes bacterial virulence gene expression during infection.

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