Mutational analysis of RetS, an unusual sensor kinase-response regulator hybrid required for Pseudomonas aeruginosa
Michelle A Laskowski1, Barbara I Kazmierczak
1Program in Microbiology, Yale University School of Medicine, 333 Cedar Street, P.O. Box 208022, New Haven, Connecticut 06520-8022, USA.
Abstract:
Pseudomonas aeruginosa is an opportunistic pathogen capable of causing both acute and chronic infections in a wide range of hosts. Expression of the type III secretion system (T3SS) proteins is correlated with virulence in models of acute infection, while downregulation of the T3SS and upregulation of genes important for biofilm formation are observed during chronic infections. RetS, a hybrid sensor kinase-response regulator protein of P. aeruginosa, plays a key role in the reciprocal regulation of virulence factors required for acute versus chronic infection and is postulated to act in concert with two other sensor kinase-response regulator hybrids, GacS and LadS. This work examines the roles of the putative sensing and signal transduction domains of RetS in induction of the T3SS in vitro and in a murine model of acute pneumonia. We identify distinct signaling roles for the tandem receiver domains of RetS and present evidence suggesting that RetS may serve as a substrate for another sensor kinase. Phenotypes associated with RetS alleles lacking periplasmic and/or transmembrane domains further indicate that the periplasmic domain of RetS may transmit a signal that inhibits RetS activity during acute infections.
Insights
Pseudomonas aeruginosa uses the RetS protein to control virulence factors for acute or chronic infections. Researchers found RetS
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Molecular Biology
Background:
- Pseudomonas aeruginosa is an opportunistic pathogen causing acute and chronic infections.
- Type III secretion system (T3SS) expression correlates with acute virulence.
- Biofilm formation genes are upregulated in chronic P. aeruginosa infections.
Purpose of the Study:
- To investigate the roles of RetS' sensing and signal transduction domains.
- To understand RetS' regulation of T3SS in acute P. aeruginosa infections.
Main Methods:
- In vitro assays to study T3SS induction.
- Murine model of acute pneumonia to assess virulence.
- Analysis of RetS alleles with deletions in specific domains.
Main Results:
- Distinct signaling roles were identified for RetS' tandem receiver domains.
- Evidence suggests RetS is a substrate for another sensor kinase.
- The periplasmic domain of RetS appears to inhibit its activity during acute infections.
Conclusions:
- RetS plays a critical role in the switch between acute and chronic virulence strategies in P. aeruginosa.
- Specific domains of RetS are crucial for its regulatory function.
- Understanding RetS signaling provides insights into P. aeruginosa pathogenesis.
More Related Videos
Related Concept Videos
Regulation of Bacterial Virulence
Gene Regulation in Microbial Communities: Quorum Sensing
Global Regulatory Systems
Other Stress Responses in Bacteria
Stringent Response in E. coli
The Ras Gene
Ras is a superfamily...


