PMID- 33172253 OWN - NLM STAT- MEDLINE DCOM- 20210527 LR - 20210527 IS - 1554-8937 (Electronic) IS - 1554-8929 (Linking) VI - 15 IP - 11 DP - 2020 Nov 20 TI - Quorum Sensing Inhibition Attenuates the Virulence of the Plant Pathogen Ralstonia solanacearum Species Complex. PG - 3050-3059 LID - 10.1021/acschembio.0c00752 [doi] AB - Strains of Ralstonia solanacearum species complex (RSSC) cause "bacterial wilt" on a wide range of plant species and thus lead to marked economic losses in agriculture. Quorum sensing (QS), a bacterial cell-cell communication mechanism, controls the virulence of RSSC strains by regulating the production of extracellular polysaccharide (EPS) and secondary metabolites, biofilm formation, and cellular motility. R. solanacearum strain OE1-1 employs (R)-methyl 3-hydroxymyristate (3-OH MAME) as a QS signal, which is synthesized by the PhcB methyltransferase and sensed by the PhcS/PhcRQ two-component system. We describe the design, synthesis, and biological evaluation of inhibitors of the phc QS system. Initial screening of a small set of QS signal analogues revealed that methyl 3-hydroxy-8-phenyloctanoate, named, PQI-1 (phc quorum sensing inhibitor-1), inhibited biofilm formation by strain OE1-1. To improve its inhibitory activity, the derivatives of PQI-1 were synthesized, and their QS inhibition activities were evaluated. PQIs-2-5 evolved from PQI-1 more strongly inhibited not only biofilm formation but also the production of ralfuranone and EPS. Furthermore, RNA-Seq analysis revealed that the PQIs effectively inhibited QS-dependent gene expression and repression in strain OE1-1. On the other hand, the PQIs did not affect the canonical QS systems of the representative reporter bacteria. These antagonists, especially PQI-5, reduced wilting symptoms of the tomato plants infected with strain OE1-1. Taken together, we suggest that targeting the phc QS system has potential for the development of chemicals that protect agricultural crops from bacterial wilt disease. FAU - Yoshihara, Ayaka AU - Yoshihara A AD - Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan. FAU - Shimatani, Mika AU - Shimatani M AD - Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan. FAU - Sakata, Megumi AU - Sakata M AD - Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan. FAU - Takemura, Chika AU - Takemura C AD - Laboratory of Plant Pathology and Biotechnology, Kochi University, 200 Otsu, Monobe, Nanko-ku, Kochi 783-8502, Japan. FAU - Senuma, Wakana AU - Senuma W AD - Laboratory of Plant Pathology and Biotechnology, Kochi University, 200 Otsu, Monobe, Nanko-ku, Kochi 783-8502, Japan. FAU - Hikichi, Yasufumi AU - Hikichi Y AD - Laboratory of Plant Pathology and Biotechnology, Kochi University, 200 Otsu, Monobe, Nanko-ku, Kochi 783-8502, Japan. FAU - Kai, Kenji AU - Kai K AUID- ORCID: 0000-0002-4036-9959 AD - Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201110 PL - United States TA - ACS Chem Biol JT - ACS chemical biology JID - 101282906 RN - 0 (Caprylates) RN - 0 (Myristates) RN - 0 (methyl 3-hydroxymyristate) SB - IM MH - Biofilms/drug effects MH - Caprylates/chemistry/*pharmacology MH - Myristates/metabolism MH - Plant Diseases/*microbiology/prevention & control MH - Quorum Sensing/*drug effects MH - Ralstonia solanacearum/*drug effects/pathogenicity MH - Virulence/drug effects EDAT- 2020/11/12 06:00 MHDA- 2021/05/28 06:00 CRDT- 2020/11/11 05:34 PHST- 2020/11/12 06:00 [pubmed] PHST- 2021/05/28 06:00 [medline] PHST- 2020/11/11 05:34 [entrez] AID - 10.1021/acschembio.0c00752 [doi] PST - ppublish SO - ACS Chem Biol. 2020 Nov 20;15(11):3050-3059. doi: 10.1021/acschembio.0c00752. Epub 2020 Nov 10.