Modulation of Type III Secretion System in Pseudomonas aeruginosa: Involvement of the PA4857 Gene Product.

Miao Zhu,Haihua Liang,Jingru Zhao,Weina Kong,Huaping Kang

doi:10.3389/fmicb.2016.00007

Abstract

Pseudomonas aeruginosa is an opportunistic pathogen that causes serious acute or chronic infections in humans. Acute infections typically involve the type III secretion systems (T3SSs) and bacterial motility, whereas chronic infections are often associated with biofilm formation and the type VI secretion system. To identify new genes required for pathogenesis, a transposon mutagenesis library was constructed and the gene PA4857, named tspR, was found to modulate T3SS gene expression. Deletion of P. aeruginosa tspR reduced the virulence in a mouse acute lung infection model and diminished cytotoxicity. Suppression of T3SS gene expression in the tspR mutant resulted from compromised translation of the T3SS master regulator ExsA. TspR negatively regulated two small RNAs, RsmY and RsmZ, which control RsmA. Our data demonstrated that defects in T3SS expression and biofilm formation in retS mutant could be partially restored by overexpression of tspR. Taken together, our results demonstrated that the newly identified retS-tspR pathway is coordinated with the retS-gacS system, which regulates the genes associated with acute and chronic infections and controls the lifestyle choice of P. aeruginosa.

Highlights

Pseudomonas aeruginosa is one of the most common nosocomial pathogens and often causes numerous acute or chronic infections (Deretic et al, 1995)
A group of known T3SS modulators including PcrD, PscC and ExsA, were isolated (Yahr et al, 1997). clpS encodes an ATP-dependent Clp protease adaptor that is associated with antibiotic resistance, motility, and biofilm formation of P. aeruginosa (Fernandez et al, 2012)
Among the 15 genes that regulate T3SS, we investigated the role of PA4857, which we designated as Type III secretion system and pathogenesis Regulator, in T3SS regulation. tspR is located immediately downstream of retS, a known regulator of T3SS gene expression and biofilm formation in P. aeruginosa (Goodman et al, 2004; Laskowski et al, 2004)

Summary

Introduction

Pseudomonas aeruginosa is one of the most common nosocomial pathogens and often causes numerous acute or chronic infections (Deretic et al, 1995). To investigate the regulatory mechanism of the T3SS, we constructed a transposon insertion library in a wildtype PAO1 strain containing an exoS-lux transcriptional reporter integrated into the chromosome at the vacant phage CTX attachment site and screened for mutants with altered exoS-lux expression.

Results

Conclusion