The AlgZR Two-Component System Recalibrates the RsmAYZ Posttranscriptional Regulatory System To Inhibit Expression of the Pseudomonas aeruginosa Type III Secretion System

Peter J Intile; Manisha R Diaz; Mark L Urbanowski; Matthew C Wolfgang; Timothy L Yahr

doi:10.1128/JB.01199-13

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The AlgZR Two-Component System Recalibrates the RsmAYZ Posttranscriptional Regulatory System To Inhibit Expression of the Pseudomonas aeruginosa Type III Secretion System

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The AlgZR Two-Component System Recalibrates the RsmAYZ Posttranscriptional Regulatory System To Inhibit Expression of the Pseudomonas aeruginosa Type III Secretion System

Peter J Intile, Manisha R Diaz, Mark L Urbanowski, Matthew C Wolfgang and Timothy L Yahr

Journal of bacteriology, Vol.196(2), pp.357-366

01/2014

DOI: 10.1128/JB.01199-13

PMCID: PMC3911257

PMID: 24187093

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Abstract

Pseudomonas aeruginosa causes chronic airway infections in cystic fibrosis (CF) patients. A classic feature of CF airway isolates is the mucoid phenotype. Mucoidy arises through mutation of the mucA anti-sigma factor and subsequent activation of the AlgU regulon. Inactivation of mucA also results in reduced expression of the Vfr transcription factor. Vfr regulates several important virulence factors, including a type III secretion system (T3SS). In the present study, we report that ExsA expression, the master regulator of T3SS gene expression, is further reduced in mucA mutants through a Vfr-independent mechanism involving the RsmAYZ regulatory system. RsmA is an RNA binding protein required for T3SS gene expression. Genetic experiments suggest that the AlgZR two-component system, part of the AlgU regulon, inhibits ExsA expression by increasing the expression of RsmY and RsmZ, two small noncoding RNAs that sequester RsmA from target mRNAs. Epistasis analyses revealed that increasing the concentration of free RsmA, through either rsmYZ deletion or increased RsmA expression, partially restored T3SS gene expression in the mucA mutant. Furthermore, increasing RsmA availability in combination with Vfr complementation fully restored T3SS expression. Recalibration of the RsmAYZ system by AlgZR, however, did not alter the expression of other selected RsmA-dependent targets. We account for this observation by showing that ExsA expression is more sensitive to changes in free RsmA than other members of the RsmA regulon. Together, these data indicate that recalibration of the RsmAYZ system partially accounts for reduced T3SS gene expression in mucA mutants.

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Title: Subtitle: The AlgZR Two-Component System Recalibrates the RsmAYZ Posttranscriptional Regulatory System To Inhibit Expression of the Pseudomonas aeruginosa Type III Secretion System
Creators: Peter J Intile - Department of Microbiology, University of Iowa, Iowa City, Iowa, USA
Manisha R Diaz - Department of Microbiology, University of Iowa, Iowa City, Iowa, USA
Mark L Urbanowski - Department of Microbiology, University of Iowa, Iowa City, Iowa, USA
Matthew C Wolfgang - Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, USA
Timothy L Yahr - Department of Microbiology, University of Iowa, Iowa City, Iowa, USA
Resource Type: Journal article
Publication Details: Journal of bacteriology, Vol.196(2), pp.357-366
Publisher: American Society for Microbiology; 1752 N St., N.W., Washington, DC
DOI: 10.1128/JB.01199-13
PMID: 24187093
PMCID: PMC3911257
ISSN: 0021-9193
eISSN: 1098-5530
Language: English
Date published: 01/2014
Academic Unit: Microbiology and Immunology
Record Identifier: 9984001201502771

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