Dataset Information

Derivatives of plant phenolic compound affect the type III secretion system of Pseudomonas aeruginosa via a GacS-GacA two-component signal transduction system.

ABSTRACT: Antibiotic therapy is the most commonly used strategy to control pathogenic infections; however, it has contributed to the generation of antibiotic-resistant bacteria. To circumvent this emerging problem, we are searching for compounds that target bacterial virulence factors rather than their viability. Pseudomonas aeruginosa, an opportunistic human pathogen, possesses a type III secretion system (T3SS) as one of the major virulence factors by which it secretes and translocates T3 effector proteins into human host cells. The fact that this human pathogen also is able to infect several plant species led us to screen a library of phenolic compounds involved in plant defense signaling and their derivatives for novel T3 inhibitors. Promoter activity screening of exoS, which encodes a T3-secreted toxin, identified two T3 inhibitors and two T3 inducers of P. aeruginosa PAO1. These compounds alter exoS transcription by affecting the expression levels of the regulatory small RNAs RsmY and RsmZ. These two small RNAs are known to control the activity of carbon storage regulator RsmA, which is responsible for the regulation of the key T3SS regulator ExsA. As RsmY and RsmZ are the only targets directly regulated by GacA, our results suggest that these phenolic compounds affect the expression of exoS through the GacSA-RsmYZ-RsmA-ExsA regulatory pathway.

SUBMITTER: Yamazaki A

PROVIDER: S-EPMC3256035 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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Derivatives of plant phenolic compound affect the type III secretion system of Pseudomonas aeruginosa via a GacS-GacA two-component signal transduction system.

Yamazaki Akihiro A Li Jin J Zeng Quan Q Khokhani Devanshi D Hutchins William C WC Yost Angela C AC Biddle Eulandria E Toone Eric J EJ Chen Xin X Yang Ching-Hong CH

Antimicrobial agents and chemotherapy 20111003 1

Antibiotic therapy is the most commonly used strategy to control pathogenic infections; however, it has contributed to the generation of antibiotic-resistant bacteria. To circumvent this emerging problem, we are searching for compounds that target bacterial virulence factors rather than their viability. Pseudomonas aeruginosa, an opportunistic human pathogen, possesses a type III secretion system (T3SS) as one of the major virulence factors by which it secretes and translocates T3 effector prote ...[more]

PMID: 21968370

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Project description:In Pseudomonas aeruginosa, the complex multisensing regulatory networks RetS-GacS/GacA have been demonstrated to play key roles in controlling the switch between planktonic and sessile lifestyles. However, whether this multisensing system is involved in the regulation of phage infection has not been investigated. Here, we provide a link between the sensors RetS/GacS and infection of phages vB_Pae_QDWS and vB_Pae_W3. Our data suggest that the sensors kinases RetS and GacS in Pseudomonas aeruginosa play opposite regulatory functions on phage infection. Mutation in retS increased phage resistance. Cellular levels of RsmY and RsmZ increased in PaΔretS and were positively correlated with phage resistance. Further analysis demonstrated that RetS regulated phage infection by affecting the type IV pilus (T4P)-mediated adsorption. The regulation of RetS on phage infection depends on the GacS/GacA two-component system and is likely a dynamic process in response to environmental signals. The findings offer additional support for the rapid emergence of phage resistance. IMPORTANCE Our knowledge on the molecular mechanisms behind bacterium-phage interactions remains limited. Our study reported that the complex multisensing regulatory networks RetS-GacS/GacA of Pseudomonas aeruginosa PAO1 play key roles in controlling phage infection. The main observation was that the mutation in RetS could result in increased phage resistance by reducing the type IV pilus-mediated phage adsorption. The bacterial defense strategy is generally applicable to various phages since many P. aeruginosa phages can use type IV pilus as their receptors. The results also suggest that the phage infection is likely to be regulated dynamically, which depends on the environmental stimuli. Reduction of the signals that RetS favors would increase phage resistance. Our study is particularly remarkable for uncovering a signal transduction system that was involved in phage infection, which may help in filling some knowledge gaps in this field.

Dataset Information

Derivatives of plant phenolic compound affect the type III secretion system of Pseudomonas aeruginosa via a GacS-GacA two-component signal transduction system.

Publications

Derivatives of plant phenolic compound affect the type III secretion system of Pseudomonas aeruginosa via a GacS-GacA two-component signal transduction system.

Similar Datasets

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