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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Main Authors: Md. Mahi Imam Mollah, Aman Dekebo, Yonggyun Kim
Format: Article
Language:English
Published: MDPI AG 2020-08-01
Series:Insects
Subjects:
Online Access:https://www.mdpi.com/2075-4450/11/8/505
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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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