Mechanism of Gene Regulation by a <named-content content-type="genus-species">Staphylococcus aureus</named-content> Toxin

ABSTRACT The virulence of many bacterial pathogens, including the important human pathogen Staphylococcus aureus, depends on the secretion of frequently large amounts of toxins. Toxin production involves the need for the bacteria to make physiological adjustments for energy conservation. While toxin...

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Autores principales:	Hwang-Soo Joo, Som S. Chatterjee, Amer E. Villaruz, Seth W. Dickey, Vee Y. Tan, Yan Chen, Daniel E. Sturdevant, Stacy M. Ricklefs, Michael Otto
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/61c33f922bf24eabbaba5dfb4d68f5fc
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spelling	oai:doaj.org-article:61c33f922bf24eabbaba5dfb4d68f5fc2021-11-15T15:50:15ZMechanism of Gene Regulation by a <named-content content-type="genus-species">Staphylococcus aureus</named-content> Toxin10.1128/mBio.01579-162150-7511https://doaj.org/article/61c33f922bf24eabbaba5dfb4d68f5fc2016-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01579-16https://doaj.org/toc/2150-7511ABSTRACT The virulence of many bacterial pathogens, including the important human pathogen Staphylococcus aureus, depends on the secretion of frequently large amounts of toxins. Toxin production involves the need for the bacteria to make physiological adjustments for energy conservation. While toxins are primarily targets of gene regulation, such changes may be accomplished by regulatory functions of the toxins themselves. However, mechanisms by which toxins regulate gene expression have remained poorly understood. We show here that the staphylococcal phenol-soluble modulin (PSM) toxins have gene regulatory functions that, in particular, include inducing expression of their own transport system by direct interference with a GntR-type repressor protein. This capacity was most pronounced in PSMs with low cytolytic capacity, demonstrating functional specification among closely related members of that toxin family during evolution. Our study presents a molecular mechanism of gene regulation by a bacterial toxin that adapts bacterial physiology to enhanced toxin production. IMPORTANCE Toxins play a major role in many bacterial diseases. When toxins are produced during infection, the bacteria need to balance this energy-consuming task with other physiological processes. However, it has remained poorly understood how toxins can impact gene expression to trigger such adaptations. We found that specific members of a toxin family in the major human pathogen Staphylococcus aureus have evolved for gene regulatory purposes. These specific toxins interact with a DNA-binding regulator protein to enable production of the toxin export machinery and ascertain that the machinery is not expressed when toxins are not made and it is not needed. Our study gives mechanistic insight into how toxins may directly adjust bacterial physiology to times of toxin production during infection.Hwang-Soo JooSom S. ChatterjeeAmer E. VillaruzSeth W. DickeyVee Y. TanYan ChenDaniel E. SturdevantStacy M. RicklefsMichael OttoAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 5 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Hwang-Soo Joo Som S. Chatterjee Amer E. Villaruz Seth W. Dickey Vee Y. Tan Yan Chen Daniel E. Sturdevant Stacy M. Ricklefs Michael Otto Mechanism of Gene Regulation by a <named-content content-type="genus-species">Staphylococcus aureus</named-content> Toxin
description	ABSTRACT The virulence of many bacterial pathogens, including the important human pathogen Staphylococcus aureus, depends on the secretion of frequently large amounts of toxins. Toxin production involves the need for the bacteria to make physiological adjustments for energy conservation. While toxins are primarily targets of gene regulation, such changes may be accomplished by regulatory functions of the toxins themselves. However, mechanisms by which toxins regulate gene expression have remained poorly understood. We show here that the staphylococcal phenol-soluble modulin (PSM) toxins have gene regulatory functions that, in particular, include inducing expression of their own transport system by direct interference with a GntR-type repressor protein. This capacity was most pronounced in PSMs with low cytolytic capacity, demonstrating functional specification among closely related members of that toxin family during evolution. Our study presents a molecular mechanism of gene regulation by a bacterial toxin that adapts bacterial physiology to enhanced toxin production. IMPORTANCE Toxins play a major role in many bacterial diseases. When toxins are produced during infection, the bacteria need to balance this energy-consuming task with other physiological processes. However, it has remained poorly understood how toxins can impact gene expression to trigger such adaptations. We found that specific members of a toxin family in the major human pathogen Staphylococcus aureus have evolved for gene regulatory purposes. These specific toxins interact with a DNA-binding regulator protein to enable production of the toxin export machinery and ascertain that the machinery is not expressed when toxins are not made and it is not needed. Our study gives mechanistic insight into how toxins may directly adjust bacterial physiology to times of toxin production during infection.
format	article
author	Hwang-Soo Joo Som S. Chatterjee Amer E. Villaruz Seth W. Dickey Vee Y. Tan Yan Chen Daniel E. Sturdevant Stacy M. Ricklefs Michael Otto
author_facet	Hwang-Soo Joo Som S. Chatterjee Amer E. Villaruz Seth W. Dickey Vee Y. Tan Yan Chen Daniel E. Sturdevant Stacy M. Ricklefs Michael Otto
author_sort	Hwang-Soo Joo
title	Mechanism of Gene Regulation by a <named-content content-type="genus-species">Staphylococcus aureus</named-content> Toxin
title_short	Mechanism of Gene Regulation by a <named-content content-type="genus-species">Staphylococcus aureus</named-content> Toxin
title_full	Mechanism of Gene Regulation by a <named-content content-type="genus-species">Staphylococcus aureus</named-content> Toxin
title_fullStr	Mechanism of Gene Regulation by a <named-content content-type="genus-species">Staphylococcus aureus</named-content> Toxin
title_full_unstemmed	Mechanism of Gene Regulation by a <named-content content-type="genus-species">Staphylococcus aureus</named-content> Toxin
title_sort	mechanism of gene regulation by a <named-content content-type="genus-species">staphylococcus aureus</named-content> toxin
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/61c33f922bf24eabbaba5dfb4d68f5fc
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Mechanism of Gene Regulation by a <named-content content-type="genus-species">Staphylococcus aureus</named-content> Toxin

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