Cyclic Diguanylate Signaling Proteins Control Intracellular Growth of <named-content content-type="genus-species">Legionella pneumophila</named-content>

ABSTRACT Proteins that metabolize or bind the nucleotide second messenger cyclic diguanylate regulate a wide variety of important processes in bacteria. These processes include motility, biofilm formation, cell division, differentiation, and virulence. The role of cyclic diguanylate signaling in the...

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Autores principales:	Assaf Levi, Marc Folcher, Urs Jenal, Howard A. Shuman
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2011
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/3a94640dd5384d75802f1f3aaf0db383
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spelling	oai:doaj.org-article:3a94640dd5384d75802f1f3aaf0db3832021-11-15T15:38:46ZCyclic Diguanylate Signaling Proteins Control Intracellular Growth of <named-content content-type="genus-species">Legionella pneumophila</named-content>10.1128/mBio.00316-102150-7511https://doaj.org/article/3a94640dd5384d75802f1f3aaf0db3832011-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00316-10https://doaj.org/toc/2150-7511ABSTRACT Proteins that metabolize or bind the nucleotide second messenger cyclic diguanylate regulate a wide variety of important processes in bacteria. These processes include motility, biofilm formation, cell division, differentiation, and virulence. The role of cyclic diguanylate signaling in the lifestyle of Legionella pneumophila, the causative agent of Legionnaires’ disease, has not previously been examined. The L. pneumophila genome encodes 22 predicted proteins containing domains related to cyclic diguanylate synthesis, hydrolysis, and recognition. We refer to these genes as cdgS (cyclic diguanylate signaling) genes. Strains of L. pneumophila containing deletions of all individual cdgS genes were created and did not exhibit any observable growth defect in growth medium or inside host cells. However, when overexpressed, several cdgS genes strongly decreased the ability of L. pneumophila to grow inside host cells. Expression of these cdgS genes did not affect the Dot/Icm type IVB secretion system, the major determinant of intracellular growth in L. pneumophila. L. pneumophila strains overexpressing these cdgS genes were less cytotoxic to THP-1 macrophages than wild-type L. pneumophila but retained the ability to resist grazing by amoebae. In many cases, the intracellular-growth inhibition caused by cdgS gene overexpression was independent of diguanylate cyclase or phosphodiesterase activities. Expression of the cdgS genes in a Salmonella enterica serovar Enteritidis strain that lacks all diguanylate cyclase activity indicated that several cdgS genes encode potential cyclases. These results indicate that components of the cyclic diguanylate signaling pathway play an important role in regulating the ability of L. pneumophila to grow in host cells. IMPORTANCE All bacteria must sense and respond to environmental cues. Intracellular bacterial pathogens must detect and respond to host functions that limit their ability to carry out a successful infection. Small-molecule second messengers play key roles in transmitting signals from environmental receptors to the proteins and other components that respond to signals. Cyclic diguanylate is a ubiquitous bacterial second messenger known to play an important role in many sensing and signaling systems in bacteria. The causative agent of Legionnaires’ disease, Legionella pneumophila, is an intracellular pathogen that grows inside environmental protists and human macrophages by subverting the normal processes that these cells use to capture and destroy bacteria. We show that the several cyclic diguanylate signaling components in Legionella play a role in the ability to grow inside both kinds of host cells. This work highlights the role of cyclic diguanylate signaling during intracellular growth.Assaf LeviMarc FolcherUrs JenalHoward A. ShumanAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 2, Iss 1 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Assaf Levi Marc Folcher Urs Jenal Howard A. Shuman Cyclic Diguanylate Signaling Proteins Control Intracellular Growth of <named-content content-type="genus-species">Legionella pneumophila</named-content>
description	ABSTRACT Proteins that metabolize or bind the nucleotide second messenger cyclic diguanylate regulate a wide variety of important processes in bacteria. These processes include motility, biofilm formation, cell division, differentiation, and virulence. The role of cyclic diguanylate signaling in the lifestyle of Legionella pneumophila, the causative agent of Legionnaires’ disease, has not previously been examined. The L. pneumophila genome encodes 22 predicted proteins containing domains related to cyclic diguanylate synthesis, hydrolysis, and recognition. We refer to these genes as cdgS (cyclic diguanylate signaling) genes. Strains of L. pneumophila containing deletions of all individual cdgS genes were created and did not exhibit any observable growth defect in growth medium or inside host cells. However, when overexpressed, several cdgS genes strongly decreased the ability of L. pneumophila to grow inside host cells. Expression of these cdgS genes did not affect the Dot/Icm type IVB secretion system, the major determinant of intracellular growth in L. pneumophila. L. pneumophila strains overexpressing these cdgS genes were less cytotoxic to THP-1 macrophages than wild-type L. pneumophila but retained the ability to resist grazing by amoebae. In many cases, the intracellular-growth inhibition caused by cdgS gene overexpression was independent of diguanylate cyclase or phosphodiesterase activities. Expression of the cdgS genes in a Salmonella enterica serovar Enteritidis strain that lacks all diguanylate cyclase activity indicated that several cdgS genes encode potential cyclases. These results indicate that components of the cyclic diguanylate signaling pathway play an important role in regulating the ability of L. pneumophila to grow in host cells. IMPORTANCE All bacteria must sense and respond to environmental cues. Intracellular bacterial pathogens must detect and respond to host functions that limit their ability to carry out a successful infection. Small-molecule second messengers play key roles in transmitting signals from environmental receptors to the proteins and other components that respond to signals. Cyclic diguanylate is a ubiquitous bacterial second messenger known to play an important role in many sensing and signaling systems in bacteria. The causative agent of Legionnaires’ disease, Legionella pneumophila, is an intracellular pathogen that grows inside environmental protists and human macrophages by subverting the normal processes that these cells use to capture and destroy bacteria. We show that the several cyclic diguanylate signaling components in Legionella play a role in the ability to grow inside both kinds of host cells. This work highlights the role of cyclic diguanylate signaling during intracellular growth.
format	article
author	Assaf Levi Marc Folcher Urs Jenal Howard A. Shuman
author_facet	Assaf Levi Marc Folcher Urs Jenal Howard A. Shuman
author_sort	Assaf Levi
title	Cyclic Diguanylate Signaling Proteins Control Intracellular Growth of <named-content content-type="genus-species">Legionella pneumophila</named-content>
title_short	Cyclic Diguanylate Signaling Proteins Control Intracellular Growth of <named-content content-type="genus-species">Legionella pneumophila</named-content>
title_full	Cyclic Diguanylate Signaling Proteins Control Intracellular Growth of <named-content content-type="genus-species">Legionella pneumophila</named-content>
title_fullStr	Cyclic Diguanylate Signaling Proteins Control Intracellular Growth of <named-content content-type="genus-species">Legionella pneumophila</named-content>
title_full_unstemmed	Cyclic Diguanylate Signaling Proteins Control Intracellular Growth of <named-content content-type="genus-species">Legionella pneumophila</named-content>
title_sort	cyclic diguanylate signaling proteins control intracellular growth of <named-content content-type="genus-species">legionella pneumophila</named-content>
publisher	American Society for Microbiology
publishDate	2011
url	https://doaj.org/article/3a94640dd5384d75802f1f3aaf0db383
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Cyclic Diguanylate Signaling Proteins Control Intracellular Growth of <named-content content-type="genus-species">Legionella pneumophila</named-content>

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