title: 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.
authors.affiliation: Department of Biological Sciences, University of Wisconsin-Milwaukee, Wisconsin 53211, USA.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yamazaki
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: Quan
authors.initials: Q
authors.lastname: Zeng
authors.forename: Devanshi
authors.initials: D
authors.lastname: Khokhani
authors.forename: William C
authors.initials: WC
authors.lastname: Hutchins
authors.forename: Angela C
authors.initials: AC
authors.lastname: Yost
authors.forename: Eulandria
authors.initials: E
authors.lastname: Biddle
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Toone
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.forename: Ching-Hong
authors.initials: CH
authors.lastname: Yang
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D058947:Bacterial Secretion Systems / Q000187:drug effects* / Q000235:genetics; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D005809:Genes, Regulator; D017930:Genes, Reporter; D057166:High-Throughput Screening Assays; D006801:Humans; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D001427:Bacterial Toxins; C091100:GacA protein, Bacteria; D010636:Phenols; D010936:Plant Extracts; D014157:Transcription Factors; D037521:Virulence Factors; C074165:lemA protein, bacterial