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FimL Regulates cAMP Synthesis in Pseudomonas aeruginosa

Pseudomonas aeruginosa, a ubiquitous bacteria found in diverse ecological niches, is an important cause of acute infections in immunocompromised individuals and chronic infections in patients with Cystic Fibrosis. One signaling molecule required for the coordinate regulation of virulence factors ass...

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Autores principales: Inclan, Yuki F., Huseby, Medora J., Engel, Joanne N.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3019171/
https://www.ncbi.nlm.nih.gov/pubmed/21264306
http://dx.doi.org/10.1371/journal.pone.0015867
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author Inclan, Yuki F.
Huseby, Medora J.
Engel, Joanne N.
author_facet Inclan, Yuki F.
Huseby, Medora J.
Engel, Joanne N.
author_sort Inclan, Yuki F.
collection PubMed
description Pseudomonas aeruginosa, a ubiquitous bacteria found in diverse ecological niches, is an important cause of acute infections in immunocompromised individuals and chronic infections in patients with Cystic Fibrosis. One signaling molecule required for the coordinate regulation of virulence factors associated with acute infections is 3′, 5′-cyclic adenosine monophosphate, (cAMP), which binds to and activates a catabolite repressor homolog, Vfr. Vfr controls the transcription of many virulence factors, including those associated with Type IV pili (TFP), the Type III secretion system (T3SS), the Type II secretion system, flagellar-mediated motility, and quorum sensing systems. We previously identified FimL, a protein with histidine phosphotransfer-like domains, as a regulator of Vfr-dependent processes, including TFP-dependent motility and T3SS function. In this study, we carried out genetic and physiologic studies to further define the mechanism of action of FimL. Through a genetic screen designed to identify suppressors of FimL, we found a putative cAMP-specific phosphodiesterase (CpdA), suggesting that FimL regulates cAMP levels. Inactivation of CpdA increases cAMP levels and restores TFP-dependent motility and T3SS function to fimL mutants, consistent with in vivo phosphodiesterase activity. By constructing combinations of double and triple mutants in the two adenylate cyclase genes (cyaA and cyaB), fimL, and cpdA, we show that ΔfimL mutants resemble ΔcyaB mutants in TM defects, decreased T3SS transcription, and decreased cAMP levels. Similar to some of the virulence factors that they regulate, we demonstrate that CyaB and FimL are polarly localized. These results reveal new complexities in the regulation of diverse virulence pathways associated with acute P. aeruginosa infections.
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spelling pubmed-30191712011-01-24 FimL Regulates cAMP Synthesis in Pseudomonas aeruginosa Inclan, Yuki F. Huseby, Medora J. Engel, Joanne N. PLoS One Research Article Pseudomonas aeruginosa, a ubiquitous bacteria found in diverse ecological niches, is an important cause of acute infections in immunocompromised individuals and chronic infections in patients with Cystic Fibrosis. One signaling molecule required for the coordinate regulation of virulence factors associated with acute infections is 3′, 5′-cyclic adenosine monophosphate, (cAMP), which binds to and activates a catabolite repressor homolog, Vfr. Vfr controls the transcription of many virulence factors, including those associated with Type IV pili (TFP), the Type III secretion system (T3SS), the Type II secretion system, flagellar-mediated motility, and quorum sensing systems. We previously identified FimL, a protein with histidine phosphotransfer-like domains, as a regulator of Vfr-dependent processes, including TFP-dependent motility and T3SS function. In this study, we carried out genetic and physiologic studies to further define the mechanism of action of FimL. Through a genetic screen designed to identify suppressors of FimL, we found a putative cAMP-specific phosphodiesterase (CpdA), suggesting that FimL regulates cAMP levels. Inactivation of CpdA increases cAMP levels and restores TFP-dependent motility and T3SS function to fimL mutants, consistent with in vivo phosphodiesterase activity. By constructing combinations of double and triple mutants in the two adenylate cyclase genes (cyaA and cyaB), fimL, and cpdA, we show that ΔfimL mutants resemble ΔcyaB mutants in TM defects, decreased T3SS transcription, and decreased cAMP levels. Similar to some of the virulence factors that they regulate, we demonstrate that CyaB and FimL are polarly localized. These results reveal new complexities in the regulation of diverse virulence pathways associated with acute P. aeruginosa infections. Public Library of Science 2011-01-11 /pmc/articles/PMC3019171/ /pubmed/21264306 http://dx.doi.org/10.1371/journal.pone.0015867 Text en Inclan et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Inclan, Yuki F.
Huseby, Medora J.
Engel, Joanne N.
FimL Regulates cAMP Synthesis in Pseudomonas aeruginosa
title FimL Regulates cAMP Synthesis in Pseudomonas aeruginosa
title_full FimL Regulates cAMP Synthesis in Pseudomonas aeruginosa
title_fullStr FimL Regulates cAMP Synthesis in Pseudomonas aeruginosa
title_full_unstemmed FimL Regulates cAMP Synthesis in Pseudomonas aeruginosa
title_short FimL Regulates cAMP Synthesis in Pseudomonas aeruginosa
title_sort fiml regulates camp synthesis in pseudomonas aeruginosa
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3019171/
https://www.ncbi.nlm.nih.gov/pubmed/21264306
http://dx.doi.org/10.1371/journal.pone.0015867
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