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.

The Role of Secretion Systems and Small Molecules in Soft-Rot Enterobacteriaceae Pathogenicity

“…syringae, E. amylovora, and D. dadantii, and the human pathogen Pseudomonas aeruginosa (156). Knowledge of induction of the PCWDE by AHL-mediated quorum sensing has led to the development of SRE-resistant plants (35), but this strategy has not been accepted for commercial use.…”

“…Based on the structure-activity relationship analysis of known T3SS inhibitors and inducers, analogs were synthesized and assayed (156). Novel compounds were identified in a compound inventory that inhibit the T3SS of different phytopathogens, including P.…”

Cultivable bacterial microbiota from choanae of free-living birds captured in Slovenia / Kultivabilna bakterijska mikrobiota iz sapišč prosto¬živečih ptic, ujetih v Sloveniji

“…These were Agrobacterium larrymoorei (Bouzar & Jones 2001), Clavibacter michiganensis (Xu et al 2010), Curtobacterium flaccumfaciens (Francis et al 2011), Plantoea agglomerans (Rezzonico et al 2010), Pseudomonas aeruginosa (Yamazaki et al 2012), Pseudomonas flavescens (Fett, Cescutti & Wijey 1996) and Rhodococcus fascians (Crespi et al 1992). Ten (40 %) birds were colonized by one plant pathogen and only one tree sparrow by two (Agrobacterium larrymoorei and Curtobacterium flaccumfaciens).…”

“…Species previously described as being associated with human infections were Acinetobacter calcoaceticus (Nonaka et al 2014), Cellulosimicrobium funkei (Petkar et al 2011), Curtobacterium citreum (Rivera et al 2012), Curtobacterium flaccumfaciens (Francis et al 2011), Exiguobacterium sibiricum (Tena et al 2014), Hafnia alvei (Gunthard & Pennekamp 1996), Microbacterium oleivorans (Kim & Lee 2012), Microbacterium resistens (Panackal 2013), Pantoea agglomerans (Rezzonico et al 2010), Pseudomonas aeruginosa (Yamazaki et al 2012), Serratia grimesii (Kumar et al 2013), Staphylococcus epidermidis (Vuong & Otto 2002) and Staphylococcus gallinarum (Tibra et al 2010). Eight out of 25 (32 %) sampled birds carried one or more human opportunistic bacteria in their choanae.…”

Synthesis and Bioactivity of Novel Inhibitors for Type III Secretion System ofPseudomonas aeruginosaPAO1

“…本实验以铜绿假单胞菌 PAO1 为实验对象, 于 30 ℃在添加有 NTA 的 LB 培养基中培养; GFP 转录融合质 粒 pAT-exoS 的构建参照文献 [23]. GFP 的检测方法参照 文献 [23].…”