<named-content content-type="genus-species">Haemophilus ducreyi</named-content> Hfq Contributes to Virulence Gene Regulation as Cells Enter Stationary Phase

ABSTRACT To adapt to stresses encountered in stationary phase, Gram-negative bacteria utilize the alternative sigma factor RpoS. However, some species lack RpoS; thus, it is unclear how stationary-phase adaptation is regulated in these organisms. Here we defined the growth-phase-dependent transcript...

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Autores principales:	Dharanesh Gangaiah, Maria Labandeira-Rey, Xinjun Zhang, Kate R. Fortney, Sheila Ellinger, Beth Zwickl, Beth Baker, Yunlong Liu, Diane M. Janowicz, Barry P. Katz, Chad A. Brautigam, Robert S. Munson, Eric J. Hansen, Stanley M. Spinola
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2014
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/8b868762f10b402fa5df26a46d706d5d
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spelling	oai:doaj.org-article:8b868762f10b402fa5df26a46d706d5d2021-11-15T15:45:11Z<named-content content-type="genus-species">Haemophilus ducreyi</named-content> Hfq Contributes to Virulence Gene Regulation as Cells Enter Stationary Phase10.1128/mBio.01081-132150-7511https://doaj.org/article/8b868762f10b402fa5df26a46d706d5d2014-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01081-13https://doaj.org/toc/2150-7511ABSTRACT To adapt to stresses encountered in stationary phase, Gram-negative bacteria utilize the alternative sigma factor RpoS. However, some species lack RpoS; thus, it is unclear how stationary-phase adaptation is regulated in these organisms. Here we defined the growth-phase-dependent transcriptomes of Haemophilus ducreyi, which lacks an RpoS homolog. Compared to mid-log-phase organisms, cells harvested from the stationary phase upregulated genes encoding several virulence determinants and a homolog of hfq. Insertional inactivation of hfq altered the expression of ~16% of the H. ducreyi genes. Importantly, there were a significant overlap and an inverse correlation in the transcript levels of genes differentially expressed in the hfq inactivation mutant relative to its parent and the genes differentially expressed in stationary phase relative to mid-log phase in the parent. Inactivation of hfq downregulated genes in the flp-tad and lspB-lspA2 operons, which encode several virulence determinants. To comply with FDA guidelines for human inoculation experiments, an unmarked hfq deletion mutant was constructed and was fully attenuated for virulence in humans. Inactivation or deletion of hfq downregulated Flp1 and impaired the ability of H. ducreyi to form microcolonies, downregulated DsrA and rendered H. ducreyi serum susceptible, and downregulated LspB and LspA2, which allow H. ducreyi to resist phagocytosis. We propose that, in the absence of an RpoS homolog, Hfq serves as a major contributor of H. ducreyi stationary-phase and virulence gene regulation. The contribution of Hfq to stationary-phase gene regulation may have broad implications for other organisms that lack an RpoS homolog. IMPORTANCE Pathogenic bacteria encounter a wide range of stresses in their hosts, including nutrient limitation; the ability to sense and respond to such stresses is crucial for bacterial pathogens to successfully establish an infection. Gram-negative bacteria frequently utilize the alternative sigma factor RpoS to adapt to stresses and stationary phase. However, homologs of RpoS are absent in some bacterial pathogens, including Haemophilus ducreyi, which causes chancroid and facilitates the acquisition and transmission of HIV-1. Here, we provide evidence that, in the absence of an RpoS homolog, Hfq serves as a major contributor of stationary-phase gene regulation and that Hfq is required for H. ducreyi to infect humans. To our knowledge, this is the first study describing Hfq as a major contributor of stationary-phase gene regulation in bacteria and the requirement of Hfq for the virulence of a bacterial pathogen in humans.Dharanesh GangaiahMaria Labandeira-ReyXinjun ZhangKate R. FortneySheila EllingerBeth ZwicklBeth BakerYunlong LiuDiane M. JanowiczBarry P. KatzChad A. BrautigamRobert S. MunsonEric J. HansenStanley M. SpinolaAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 5, Iss 1 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Dharanesh Gangaiah Maria Labandeira-Rey Xinjun Zhang Kate R. Fortney Sheila Ellinger Beth Zwickl Beth Baker Yunlong Liu Diane M. Janowicz Barry P. Katz Chad A. Brautigam Robert S. Munson Eric J. Hansen Stanley M. Spinola <named-content content-type="genus-species">Haemophilus ducreyi</named-content> Hfq Contributes to Virulence Gene Regulation as Cells Enter Stationary Phase
description	ABSTRACT To adapt to stresses encountered in stationary phase, Gram-negative bacteria utilize the alternative sigma factor RpoS. However, some species lack RpoS; thus, it is unclear how stationary-phase adaptation is regulated in these organisms. Here we defined the growth-phase-dependent transcriptomes of Haemophilus ducreyi, which lacks an RpoS homolog. Compared to mid-log-phase organisms, cells harvested from the stationary phase upregulated genes encoding several virulence determinants and a homolog of hfq. Insertional inactivation of hfq altered the expression of ~16% of the H. ducreyi genes. Importantly, there were a significant overlap and an inverse correlation in the transcript levels of genes differentially expressed in the hfq inactivation mutant relative to its parent and the genes differentially expressed in stationary phase relative to mid-log phase in the parent. Inactivation of hfq downregulated genes in the flp-tad and lspB-lspA2 operons, which encode several virulence determinants. To comply with FDA guidelines for human inoculation experiments, an unmarked hfq deletion mutant was constructed and was fully attenuated for virulence in humans. Inactivation or deletion of hfq downregulated Flp1 and impaired the ability of H. ducreyi to form microcolonies, downregulated DsrA and rendered H. ducreyi serum susceptible, and downregulated LspB and LspA2, which allow H. ducreyi to resist phagocytosis. We propose that, in the absence of an RpoS homolog, Hfq serves as a major contributor of H. ducreyi stationary-phase and virulence gene regulation. The contribution of Hfq to stationary-phase gene regulation may have broad implications for other organisms that lack an RpoS homolog. IMPORTANCE Pathogenic bacteria encounter a wide range of stresses in their hosts, including nutrient limitation; the ability to sense and respond to such stresses is crucial for bacterial pathogens to successfully establish an infection. Gram-negative bacteria frequently utilize the alternative sigma factor RpoS to adapt to stresses and stationary phase. However, homologs of RpoS are absent in some bacterial pathogens, including Haemophilus ducreyi, which causes chancroid and facilitates the acquisition and transmission of HIV-1. Here, we provide evidence that, in the absence of an RpoS homolog, Hfq serves as a major contributor of stationary-phase gene regulation and that Hfq is required for H. ducreyi to infect humans. To our knowledge, this is the first study describing Hfq as a major contributor of stationary-phase gene regulation in bacteria and the requirement of Hfq for the virulence of a bacterial pathogen in humans.
format	article
author	Dharanesh Gangaiah Maria Labandeira-Rey Xinjun Zhang Kate R. Fortney Sheila Ellinger Beth Zwickl Beth Baker Yunlong Liu Diane M. Janowicz Barry P. Katz Chad A. Brautigam Robert S. Munson Eric J. Hansen Stanley M. Spinola
author_facet	Dharanesh Gangaiah Maria Labandeira-Rey Xinjun Zhang Kate R. Fortney Sheila Ellinger Beth Zwickl Beth Baker Yunlong Liu Diane M. Janowicz Barry P. Katz Chad A. Brautigam Robert S. Munson Eric J. Hansen Stanley M. Spinola
author_sort	Dharanesh Gangaiah
title	<named-content content-type="genus-species">Haemophilus ducreyi</named-content> Hfq Contributes to Virulence Gene Regulation as Cells Enter Stationary Phase
title_short	<named-content content-type="genus-species">Haemophilus ducreyi</named-content> Hfq Contributes to Virulence Gene Regulation as Cells Enter Stationary Phase
title_full	<named-content content-type="genus-species">Haemophilus ducreyi</named-content> Hfq Contributes to Virulence Gene Regulation as Cells Enter Stationary Phase
title_fullStr	<named-content content-type="genus-species">Haemophilus ducreyi</named-content> Hfq Contributes to Virulence Gene Regulation as Cells Enter Stationary Phase
title_full_unstemmed	<named-content content-type="genus-species">Haemophilus ducreyi</named-content> Hfq Contributes to Virulence Gene Regulation as Cells Enter Stationary Phase
title_sort	<named-content content-type="genus-species">haemophilus ducreyi</named-content> hfq contributes to virulence gene regulation as cells enter stationary phase
publisher	American Society for Microbiology
publishDate	2014
url	https://doaj.org/article/8b868762f10b402fa5df26a46d706d5d
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<named-content content-type="genus-species">Haemophilus ducreyi</named-content> Hfq Contributes to Virulence Gene Regulation as Cells Enter Stationary Phase

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