Immunosuppressive Activities of Novel PLA<sub>2</sub> Inhibitors from <i>Xenorhabdus hominickii</i>, an Entomopathogenic Bacterium
Eicosanoids mediate both cellular and humoral immune responses in insects. Phospholipase A<sub>2</sub> (PLA<sub>2</sub>) catalyzes the first committed step in eicosanoid biosynthesis. It is a common pathogenic target of two entomopathogenic bacteria, <i>Xenorhabdus</...
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MDPI AG
2020-08-01
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author | Md. Mahi Imam Mollah Aman Dekebo Yonggyun Kim |
author_facet | Md. Mahi Imam Mollah Aman Dekebo Yonggyun Kim |
author_sort | Md. Mahi Imam Mollah |
collection | DOAJ |
description | Eicosanoids mediate both cellular and humoral immune responses in insects. Phospholipase A<sub>2</sub> (PLA<sub>2</sub>) catalyzes the first committed step in eicosanoid biosynthesis. It is a common pathogenic target of two entomopathogenic bacteria, <i>Xenorhabdus</i> and <i>Photorhabdus</i>. The objective of this study was to identify novel PLA<sub>2</sub> inhibitors from <i>X. hominickii</i> and determine their immunosuppressive activities. To identify novel PLA<sub>2</sub> inhibitors, stepwise fractionation of <i>X. hominickii</i> 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 PLA<sub>2</sub> in hemocytes of a lepidopteran insect, <i>Spodoptera exigua</i>, in a dose-dependent manner. They also showed significant inhibitory activities against immune responses such as prophenoloxidase activation and hemocytic nodulation of <i>S. exigua</i> larvae, with PM and EMP exhibiting the most potent inhibitory activities. These immunosuppressive activities were specific through PLA<sub>2</sub> inhibition because an addition of arachidonic acid, a catalytic product of PLA<sub>2</sub>, 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 <i>Bacillus thuringiensis</i> (Bt), they markedly increased Bt pathogenicity. This study identified eight PLA<sub>2</sub> inhibitors from bacterial metabolites of <i>X. hominickii</i> and demonstrated their potential as novel insecticides. |
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spelling | doaj.art-8157763292a541cda8a2e18bbeb5e3db2023-11-20T09:04:54ZengMDPI AGInsects2075-44502020-08-0111850510.3390/insects11080505Immunosuppressive Activities of Novel PLA<sub>2</sub> Inhibitors from <i>Xenorhabdus hominickii</i>, an Entomopathogenic BacteriumMd. Mahi Imam Mollah0Aman Dekebo1Yonggyun Kim2Department of Plant Medicals, College of Natural Sciences, Andong National University, Andong 36729, KoreaDepartment of Applied Chemistry, Adama Science and Technology University, P.O. Box 1888 Adama, EthiopiaDepartment of Plant Medicals, College of Natural Sciences, Andong National University, Andong 36729, KoreaEicosanoids mediate both cellular and humoral immune responses in insects. Phospholipase A<sub>2</sub> (PLA<sub>2</sub>) catalyzes the first committed step in eicosanoid biosynthesis. It is a common pathogenic target of two entomopathogenic bacteria, <i>Xenorhabdus</i> and <i>Photorhabdus</i>. The objective of this study was to identify novel PLA<sub>2</sub> inhibitors from <i>X. hominickii</i> and determine their immunosuppressive activities. To identify novel PLA<sub>2</sub> inhibitors, stepwise fractionation of <i>X. hominickii</i> 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 PLA<sub>2</sub> in hemocytes of a lepidopteran insect, <i>Spodoptera exigua</i>, in a dose-dependent manner. They also showed significant inhibitory activities against immune responses such as prophenoloxidase activation and hemocytic nodulation of <i>S. exigua</i> larvae, with PM and EMP exhibiting the most potent inhibitory activities. These immunosuppressive activities were specific through PLA<sub>2</sub> inhibition because an addition of arachidonic acid, a catalytic product of PLA<sub>2</sub>, 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 <i>Bacillus thuringiensis</i> (Bt), they markedly increased Bt pathogenicity. This study identified eight PLA<sub>2</sub> inhibitors from bacterial metabolites of <i>X. hominickii</i> and demonstrated their potential as novel insecticides.https://www.mdpi.com/2075-4450/11/8/505PLA<sub>2</sub>eicosanoid<i>Xenorhabdus hominickii</i>insecticideimmunity |
spellingShingle | Md. Mahi Imam Mollah Aman Dekebo Yonggyun Kim Immunosuppressive Activities of Novel PLA<sub>2</sub> Inhibitors from <i>Xenorhabdus hominickii</i>, an Entomopathogenic Bacterium Insects PLA<sub>2</sub> eicosanoid <i>Xenorhabdus hominickii</i> insecticide immunity |
title | Immunosuppressive Activities of Novel PLA<sub>2</sub> Inhibitors from <i>Xenorhabdus hominickii</i>, an Entomopathogenic Bacterium |
title_full | Immunosuppressive Activities of Novel PLA<sub>2</sub> Inhibitors from <i>Xenorhabdus hominickii</i>, an Entomopathogenic Bacterium |
title_fullStr | Immunosuppressive Activities of Novel PLA<sub>2</sub> Inhibitors from <i>Xenorhabdus hominickii</i>, an Entomopathogenic Bacterium |
title_full_unstemmed | Immunosuppressive Activities of Novel PLA<sub>2</sub> Inhibitors from <i>Xenorhabdus hominickii</i>, an Entomopathogenic Bacterium |
title_short | Immunosuppressive Activities of Novel PLA<sub>2</sub> Inhibitors from <i>Xenorhabdus hominickii</i>, an Entomopathogenic Bacterium |
title_sort | immunosuppressive activities of novel pla sub 2 sub inhibitors from i xenorhabdus hominickii i an entomopathogenic bacterium |
topic | PLA<sub>2</sub> eicosanoid <i>Xenorhabdus hominickii</i> insecticide immunity |
url | https://www.mdpi.com/2075-4450/11/8/505 |
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