{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T21:33:17Z","timestamp":1791495197827,"version":"4.3.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009467","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T00:00:00Z","timestamp":1617667200000}}],"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T00:00:00Z","timestamp":1616630400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2017R1A2B3009815"],"award-info":[{"award-number":["2017R1A2B3009815"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p><jats:italic>Xenorhabdus hominickii<\/jats:italic>, an entomopathogenic bacterium, inhibits eicosanoid biosynthesis of target insects to suppress their immune responses by inhibiting phospholipase A<jats:sub>2<\/jats:sub> (PLA<jats:sub>2<\/jats:sub>) through binding to a damage-associated molecular pattern (DAMP) molecule called dorsal switch protein 1 (DSP1) from <jats:italic>Spodoptera exigua<\/jats:italic>, a lepidopteran insect. However, the signalling pathway between DSP1 and PLA<jats:sub>2<\/jats:sub> remains unknown. The objective of this study was to determine whether DSP1 could activate Toll immune signalling pathway to activate PLA<jats:sub>2<\/jats:sub> activation and whether <jats:italic>X<\/jats:italic>. <jats:italic>hominickii<\/jats:italic> metabolites could inhibit DSP1 to shutdown eicosanoid biosynthesis. Toll-Sp\u00e4tzle (Spz) signalling pathway includes two Spz (<jats:italic>SeSpz1<\/jats:italic> and <jats:italic>SeSpz2<\/jats:italic>) and 10 Toll receptors (<jats:italic>SeToll1-10<\/jats:italic>) in <jats:italic>S<\/jats:italic>. <jats:italic>exigua<\/jats:italic>. Loss-of-function approach using RNA interference showed that SeSpz1 and SeToll9 played crucial roles in connecting DSP1 mediation to activate PLA<jats:sub>2<\/jats:sub>. Furthermore, a deletion mutant against <jats:italic>SeToll9<\/jats:italic> using CRISPR\/Cas9 abolished DSP1 mediation and induced significant immunosuppression. Organic extracts of <jats:italic>X<\/jats:italic>. <jats:italic>hominickii<\/jats:italic> culture broth could bind to DSP1 at a low micromolar range. Subsequent sequential fractionations along with binding assays led to the identification of seven potent compounds including 3-ethoxy-4-methoxyphenol (EMP). EMP could bind to DSP1 and prevent its translocation to plasma in response to bacterial challenge and suppress the up-regulation of PLA<jats:sub>2<\/jats:sub> activity. These results suggest that <jats:italic>X<\/jats:italic>. <jats:italic>hominickii<\/jats:italic> inhibits DSP1 and prevents its DAMP role in activating Toll immune signalling pathway including PLA<jats:sub>2<\/jats:sub> activation, leading to significant immunosuppression of target insects.<\/jats:p>","DOI":"10.1371\/journal.ppat.1009467","type":"journal-article","created":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T20:34:30Z","timestamp":1616704470000},"page":"e1009467","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":35,"title":["Immune mediation of HMG-like DSP1 via Toll-Sp\u00e4tzle pathway and its specific inhibition by salicylic acid analogs"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1822-8076","authenticated-orcid":true,"given":"Md. 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