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Immunosuppressive Activities of Novel PLA2 Inhibitors from Xenorhabdus hominickii, an Entomopathogenic Bacterium.

ABSTRACT: Eicosanoids mediate both cellular and humoral immune responses in insects. Phospholipase A2 (PLA2) catalyzes the first committed step in eicosanoid biosynthesis. It is a common pathogenic target of two entomopathogenic bacteria, Xenorhabdus and Photorhabdus. The objective of this study was to identify novel PLA2 inhibitors from X. hominickii and determine their immunosuppressive activities. To identify novel PLA2 inhibitors, stepwise fractionation of X. hominickii culture broth and subsequent enzyme assays were performed. Eight purified fractions of bacterial metabolites were obtained. Gas chromatography and mass spectrometry (GC-MS) analysis predicted that the main components in these eight fractions were 2-cyanobenzoic acid, dibutylamine, 2-ethyl 1-hexanol, phthalimide (PM), dioctyl terephthalate, docosane, bis (2-ethylhexyl) phthalate, and 3-ethoxy-4-methoxyphenol (EMP). Their synthetic compounds inhibited the activity of PLA2 in hemocytes of a lepidopteran insect, Spodoptera exigua, in a dose-dependent manner. They also showed significant inhibitory activities against immune responses such as prophenoloxidase activation and hemocytic nodulation of S. exigua larvae, with PM and EMP exhibiting the most potent inhibitory activities. These immunosuppressive activities were specific through PLA2 inhibition because an addition of arachidonic acid, a catalytic product of PLA2, significantly rescued such suppressed immune responses. The two most potent compounds (PM and EMP) showed significant insecticidal activities after oral administration. When the compounds were mixed with Bacillus thuringiensis (Bt), they markedly increased Bt pathogenicity. This study identified eight PLA2 inhibitors from bacterial metabolites of X. hominickii and demonstrated their potential as novel insecticides.

SUBMITTER: Mollah MMI

PROVIDER: S-EPMC7469199 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Immunosuppressive Activities of Novel PLA2 Inhibitors from Xenorhabdus hominickii, an Entomopathogenic Bacterium.

Mollah Md Mahi Imam MMI Dekebo Aman A Kim Yonggyun Y

Insects 20200804 8

Eicosanoids mediate both cellular and humoral immune responses in insects. Phospholipase A2 (PLA2) catalyzes the first committed step in eicosanoid biosynthesis. It is a common pathogenic target of two entomopathogenic bacteria, Xenorhabdus and Photorhabdus. The objective of this study was to identify novel PLA2 inhibitors from X. hominickii and determine their immunosuppressive activities. To identify novel PLA2 inhibitors, stepwi ...[more]

PMID: 32759864

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Project description:Three bacterial strains, XENO-2T, XENO-7T, and XENO-10T, isolated from Steinernema entomopathogenic nematodes, were found to represent novel Xenorhabdus species. In this study, we describe these new species by whole-genome and whole-proteome phylogenomic reconstructions, by calculating sequence identity scores using core genome sequences, and by phenotypic characterization. Phylogenomic reconstructions using ribosomal and house-keeping genes, and whole-genome and whole-proteome sequences show that XENO-2T and XENO-10T are closely related to Xenorhabdus japonica DSM 16522T and that XENO-7T is closely related to Xenorhabdus bovienii subsp. africana XENO-1T and to X. bovienii subsp. bovienii T228T. The dDDH values between XENO-2T and XENO-10T and between XENO-2T and X. japonica DSM 16522T are 56.4 and 51.8%, respectively. The dDDH value between XENO-10T and X. japonica DSM 16522T is 53.4%. The dDDH values between XENO-7T and X. bovienii subsp. africana XENO-1T and between XENO-7T and X. bovienii subsp. bovienii T228T are 63.6 and 69.4%, respectively. These dDDH values are below the 70% divergence threshold for prokaryotic species delineation. The newly described species are highly pathogenic to G. mellonella larvae, grow at pH between 5 and 9 (optimum 5-7), at salt concentrations of 1-3% (optimum 1-2%), and temperatures between 20 and 37 °C (optimum 28-30 °C). Biochemical tests such as lysine decarboxylase, ornithine decarboxylase, urease, gelatinase, citrate utilization, indole and acetoin production, and cytochrome oxidase tests allow to differentiate the novel species from their more closely related species. Considering these genetic and phenotypic divergencies, we propose the following new species: Xenorhabdus aichiensis sp. nov. with XENO-7T (= CCM 9233T = CCOS 2024T) as the type strain, Xenorhabdus anantnagensis sp. nov., with XENO-2T (= CCM 9237T = CCOS 2023T) as the type strain, and Xenorhabdus yunnanensis sp. nov., with XENO-10T (= CCM 9322T = CCOS 2071T) as the type strain. Our study contributes to a better understanding of the biodiversity and phylogenetic relationships of entomopathogenic bacteria associated with insect parasitic nematodes.

Dataset Information

Immunosuppressive Activities of Novel PLA2 Inhibitors from Xenorhabdus hominickii, an Entomopathogenic Bacterium.

Publications

Immunosuppressive Activities of Novel PLA<sub>2</sub> Inhibitors from <i>Xenorhabdus hominickii</i>, an Entomopathogenic Bacterium.

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