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Helge B. Bode - One of the best experts on this subject based on the ideXlab platform.

  • Structure and biosynthesis of deoxy-polyamine in X. bovienii.
    Journal of industrial microbiology & biotechnology, 2021
    Co-Authors: Sebastian Wenski, Natalie Berghaus, Nadine Keller, Helge B. Bode
    Abstract:

    Polyamine moieties have been described as part of the fabclavine and zeamine family of natural products. While the corresponding biosynthetic gene clusters have been found in many different proteobacteria, a unique BGC was identified in the Entomopathogenic Bacterium Xenorhabdus bovienii. Mass spectrometric analysis of a X. bovienii mutant strain revealed a new deoxy-polyamine. The corresponding biosynthesis includes two additional reductive steps, initiated by an additional dehydratase (DH) domain, which was not found in any other Xenorhabdus strain. Moreover, this DH domain could be successfully integrated into homologous biosynthesis pathways, leading to the formation of other deoxy-polyamines. Additional heterologous production experiments revealed that the DH domain could act in cis as well as in trans.

  • Dual phenazine gene clusters enable diversification during biosynthesis
    Nature Chemical Biology, 2019
    Co-Authors: Yi-ming Shi, Margaretha A. Westphalen, Nick Neubacher, Nicholas J. Tobias, Alexander O Brachmann, Helge B. Bode
    Abstract:

    Biosynthetic gene clusters (BGCs) bridging genotype and phenotype continuously evolve through gene mutations and recombinations to generate chemical diversity. Phenazine BGCs are widespread in bacteria, and the biosynthetic mechanisms of the formation of the phenazine structural core have been illuminated in the last decade. However, little is known about the complex phenazine core-modification machinery. Here, we report the diversity-oriented modifications of the phenazine core through two distinct BGCs in the Entomopathogenic Bacterium Xenorhabdus szentirmaii , which lives in symbiosis with nematodes. A previously unidentified aldehyde intermediate, which can be modified by multiple enzymatic and non-enzymatic reactions, is a common intermediate bridging the pathways encoded by these BGCs. Evaluation of the antibiotic activity of the resulting phenazine derivatives suggests a highly effective strategy to convert Gram-positive specific phenazines into broad-spectrum antibiotics, which might help the bacteria–nematode complex to maintain its special environmental niche.Enzymes from two discrete biosynthetic gene clusters in the Entomopathogenic Bacterium Xenorhabdus szentirmaii cooperate to produce a diverse array of phenazine natural products, including phenazine–peptide and phenazine–polyketide derivatives.

  • the benzodiazepine like natural product tilivalline is produced by the Entomopathogenic Bacterium xenorhabdus eapokensis
    PLOS ONE, 2018
    Co-Authors: Hendrik Wolff, Helge B. Bode
    Abstract:

    : The pyrrolobenzodiazepine tilivalline (1) was originally identified in the human gut pathobiont Klebsiella oxytoca, the causative agent of antibiotic-associated hemorrhagic colitis. Here we show the identification of tilivalline and analogs thereof in the Entomopathogenic Bacterium Xenorhabdus eapokensis as well as the identification of its biosynthesis gene cluster encoding a bimodular non-ribosomal peptide synthetase. Heterologous expression of both genes in E. coli resulted in the production of 1 and from mutasynthesis and precursor directed biosynthesis 11 new tilivalline analogs were identified in X. eapokensis. These results allowed the prediction of the tilivalline biosynthesis being similar to that in K. oxytoca.

  • bioprospecting for secondary metabolites in the Entomopathogenic Bacterium photorhabdus luminescens subsp sonorensis
    Journal of Invertebrate Pathology, 2016
    Co-Authors: Rousel A Orozco, Helge B. Bode, Istvan Molnar, Patricia S Stock
    Abstract:

    Abstract Crude extracts of in vitro and in vivo cultures of two strains of Photorhabdus l. sonorensis (Enterobacteriaceae) were analyzed by TLC, HPLC-UV and LC-MS. Nine unique compounds with mass/charge ratios ( m / z ) ranging from 331.3 to 713.5 were found in MS analyses. Bioactivity of extracts was assessed on a selection of plant pathogens/pests and non-target species. Caborca strain extracts showed the highest activity against Helicoverpa zea (Lepidoptera: Noctuidae) neonates at all concentrations tested. Mortality ranged from 11% (at 10 μg/ml) to 37% (at 40 μg/ml). Strain CH35 extracts showed the highest nematicidal activity on Meloidogyne incognita (Tylenchida: Meloidogynidae) at 40 μg/ml. Low to no nematicidal activity was observed against the non-target species Steinernema carpocapsae (Rhabditida: Steinernematidae) and Caenorhabditis elegans (Rhabditida: Rhabditidae). Caborca extracts exhibited a strong antibiotic effect on Pseudomonas syringae (Pseudomonadales: Pseudomonadacedae) at 40 μg/ml, while both Caborca and CH35 extracts inhibited the growth of Bacillus subitillis (Bacillales: Bacillaceae) at 40 μg/ml. All extracts strongly inhibited the growth of the fungus Fusarium oxysporum (Hypocreales: Nectriceae) but not that of Alternaria alternata (Pleosporales: Pleosporaceae). Contrastingly, a moderate to high inhibitory effect was denoted on the non-target biocontrol fungus Beauveria bassiana (Hypocreales: Clavivipitaceae).

  • Structure Elucidation and Activity of Kolossin A, the D-/L-Pentadecapeptide Product of a Giant Nonribosomal Peptide Synthetase†
    Angewandte Chemie (International ed. in English), 2015
    Co-Authors: Helge B. Bode, Alexander O Brachmann, Marcel Kaiser, Kirtikumar B. Jadhav, Lydia Seyfarth, Christina Dauth, Sebastian W. Fuchs, Nicholas R. Waterfield, Holger Sack, Stefan H. Heinemann
    Abstract:

    The largest continuous bacterial nonribosomal peptide synthetase discovered so far is described. It consists of 15 consecutive modules arising from an uninterrupted, fully functional gene in the Entomopathogenic Bacterium Photorhabdus luminescens. The identification of its cryptic biosynthesis product was achieved by using a combination of genome analysis, promoter exchange, isotopic labeling experiments, and total synthesis of a focused collection of peptide candidates. Although it belongs to the growing class of D-/ L-peptide natural products, the encoded metabolite kolossin A was found to be largely devoid of antibiotic activity and is likely involved in interspecies communication. A stereoisomer of this peculiar natural product displayed high activity against Trypanosoma brucei rhodesiense, a recalcitrant parasite that causes the deadly disease African sleeping sickness.

Yonggyun Kim - One of the best experts on this subject based on the ideXlab platform.

  • Immunosuppressive Activities of Novel PLA2 Inhibitors from Xenorhabdus hominickii, an Entomopathogenic Bacterium.
    Insects, 2020
    Co-Authors: Mahi Imam Mollah, Aman Dekebo, Yonggyun Kim
    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.

  • Specific inhibition of Xenorhabdus hominickii, an Entomopathogenic Bacterium, against different types of host insect phospholipase A2.
    Journal of invertebrate pathology, 2017
    Co-Authors: Sadekuzzaman, Yonggyun Kim
    Abstract:

    Abstract Phospholipase A 2 (PLA 2 ) hydrolyzes ester bond of phospholipids at the sn-2 position to release free fatty acid and lysophospholipids. Some PLA 2 s preferentially release arachidonic acid which is subsequently oxygenated into eicosanoids to mediate immune responses in insects. Xenorhabdus hominickii is an Entomopathogenic Bacterium that can suppress insect immunity by inhibiting PLA 2 activity. However, little is known about target PLA 2 types inhibited by X. hominickii. Therefore, the objective of this study was to determine PLA 2 types in the host insect, Spodoptera exigua using specific inhibitors. All developmental stages of S. exigua possessed significant PLA 2 activities, with late larval stages showing relatively higher PLA 2 activities. In different larval tissues, hemocytes had higher PLA 2 activities than fat body, gut, or epidermis. Various developmental and tissue extracts exhibited differential susceptibilities to three different PLA 2 inhibitors. Late larva-to-adult stages were highly susceptible to all three different types of PLA 2 inhibitors. In contrast, extracts from egg and young larval stages were not susceptible to secretory PLA 2 (sPLA 2 ) or calcium-independent cellular PLA 2 (iPLA 2 ) inhibitors, although they were susceptible to a calcium-dependent cellular PLA 2 (cPLA 2 ) inhibitor in a dose-dependent manner. Different tissues of fifth instars exhibited variation in susceptibility to inhibitors, with epidermal tissue being sensitive to cPLA 2 inhibitor only while other tissues were sensitive to all three types of inhibitors. Bacterial challenge with heat-killed X. hominickii significantly increased PLA 2 activity. However, live bacteria suppressed the induction of PLA 2 activity. An organic extract of X. hominickii -culture broth inhibited the susceptibility of S. exigua to sPLA 2 - and iPLA 2 - specific inhibitors, but not to cPLA 2 -specific inhibitor. Oxindole, a component of the organic extract, exhibited an inhibitory pattern similar to the organic extract. Taken together, our results indicate that S. exigua possesses different PLA 2 types and that X. hominickii can inhibit PLA 2 s susceptible to sPLA 2 - and iPLA 2 - specific inhibitors .

  • Development of a high efficient "Dual Bt-Plus" insecticide using a primary form of an Entomopathogenic Bacterium, Xenorhabdus nematophila
    Journal of Microbiology and Biotechnology, 2014
    Co-Authors: Seonghyeon Eom, Hyeonghwan Kim, Youngjin Park, Yonggyun Kim
    Abstract:

    A phase variation has been reported in an Entomopathogenic Bacterium, Xenorhabdus nematophila. Compared with a wild-type primary form, a secondary form usually loses several physiological and biochemical characters. This study showed that the phase variation of X. nematophila caused a significant alteration in its immunosuppressive activity and subsequent Entomopathogenicity. A secondary form of X. nematophila was detected in laboratory colonies and exhibited significant differences in dye absorption and Entomopathogenicity. In addition, the secondary form was different in its production of eicosanoid-biosynthesis inhibitors (EBIs) compared with the primary form of X. nematophila. Production of oxindole and phydroxypropionic acid was significantly reduced in the culture broth of the secondary form of X. nematophila. The reduced EBI production resulted in significant suppression in the inhibitory effects on cellular nodule formation and phenoloxidase activity. Culture broth of the primary form of X. nematophila enhanced the pathogenicity of Bacillus thuringiensis ( Bt) significantly more than the culture broth of the secondary form. Furthermore, this study developed a highly efficient "Dual Bt-Plus" to control both lepidopteran insect pests Plutella xylostella and Spodoptera exigua, by mixing two effective Bt strains along with the addition of potent bacterial metabolites or 100-fold concentrated X. nematophila culture broth.

  • enhanced pathogenicity of bacillus thuringiensis mixed with a culture broth of an Entomopathogenic Bacterium xenorhabdus sp
    Korean Journal of Applied Entomology, 2012
    Co-Authors: Samyeol Seo, Seonghyeon Eom, Haetnim Ahn, Jiyoung Park, Yonggyun Kim
    Abstract:

    The Entomopathogenic Bacterium, sp., was isolated from an Entomopathogenic nematode, . When these bacteria were injected into the hemocoel of the diamondback moth, , they caused significant mortality. However, the Bacterium was not pathogenic when it was administered orally. This study showed that sp. significantly enhanced oral pathogenicity of (Bt) against the last instar larvae of . Different ratios of culture broth of sp. and Bt showed significantly different pathogenicities against . In field tests, the optimal bacterial mixture significantly enhanced control efficacy against compared to Bt treatment alone. These results demonstrated that sp. culture broth can be developed as a potent biopesticide by enhancing the insecticidal efficacy of Bt.

  • Three metabolites from an Entomopathogenic Bacterium, Xenorhabdus nematophila, inhibit larval development of Spodoptera exigua (Lepidoptera: Noctuidae) by inhibiting a digestive enzyme, phospholipase A2
    Insect Science, 2010
    Co-Authors: Jaehyun Kim, Yonggyun Kim
    Abstract:

    An Entomopathogenic Bacterium, Xenorhabdus nematophila, has been known to induce significant immunosuppression of target insects by inhibiting immune-associated phospholipase A2 (PLA2), which subsequently shuts down biosynthesis of eicosanoids that are critical in immune mediation in insects. Some metabolites originated from the bacterial culture broth have been identified and include benzylideneacetone, proline-tyrosine and acetylated phenylalanine-glycine-valine, which are known to inhibit enzyme activity of PLA2 extracted from hemocyte and fat body. This study tested their effects on digestive PLA2 of the beet armyworm, Spodoptera exigua. Young larvae fed different concentrations of the three metabolites resulted in significant adverse effects on larval development even at doses below 100 μg/mL. In particular, they induced significant reduction in digestive efficiency of ingested food. All three metabolites significantly inhibited catalytic activity of digestive PLA2 extracted from midgut lumen of the fifth instar larvae at a low micromolar range. These results suggest that the inhibitory activities of the three bacterial metabolites on digestive PLA2 of S. exigua midgut may explain some of their oral toxic effects.

Yuriy A. Knirel - One of the best experts on this subject based on the ideXlab platform.

Sony Shrestha - One of the best experts on this subject based on the ideXlab platform.

  • bacterial metabolites of an Entomopathogenic Bacterium xenorhabdus nematophila inhibit a catalytic activity of phenoloxidase of the diamondback moth plutella xylostella
    Journal of Microbiology and Biotechnology, 2011
    Co-Authors: Chrisitine Jisso Song, Sony Shrestha
    Abstract:

    : A monoterpenoid compound, benzylideneacetone (BZA), is identified from bacterial metabolites synthesized by an Entomopathogenic Bacterium, Xenorhabdus nematophila. It inhibits phospholipase A2 of target insects to shut down biosynthesis of various eicosanoids, which play significant roles in insect immunity. This study discovered another novel activity of BZA that directly inhibited phenoloxidase (PO) activity required for immune-associated melanization. When it was injected into larvae of Plutella xylostella, it suppressed PO activity in the plasma by inhibiting its activation from inactive proPO. However, BZA did not influence on gene expression of PO, which was analyzed by RT-PCR using gene-specific primers designed from a partial cDNA sequence of PO of the P. xylostella identified in this study. To test a direct inhibitory activity of BZA against PO, the activated PO of P. xylostella was prepared from the hemolymph collected from the larvae challenged by bacteria. When the activated PO was incubated in vitro with BZA, it was inhibited in a dose-dependent manner. The inhibition of PO by BZA was recovered by addition of increasing amounts of substrate, L-3,4-dihydroxyphenylalanine. Three other known bacterial metabolites containing a benzene propane core structure synthesized by X. nematophila also inhibited the PO enzyme activity. However, modification of the core structure by hydroxylation of BZA lost its strong inhibitory activity against the activated PO.

  • biochemical characteristics of immune associated phospholipase a2 and its inhibition by an Entomopathogenic Bacterium xenorhabdus nematophila
    Journal of Microbiology, 2009
    Co-Authors: Sony Shrestha
    Abstract:

    An Entomopathogenic Bacterium, Xenorhabdus nematophila, induces an immunosuppression of target insects by inhibiting phospholipase A2 (PLA2) activity. Recently, an immune-associated PLA2 gene was identified from the red flour beetle, Tribolium castaneum. This study cloned this PLA2 gene in a bacterial expression vector to produce a recombinant enzyme. The recombinant T. castaneum PLA2 (TcPLA2) exhibited its characteristic enzyme activity with substrate concentration, pH, and ambient temperature. Its biochemical characteristics matched to a secretory type of PLA2 (sPLA2) because its activity was inhibited by dithiothreitol (a reducing agent of disulfide bond) and bromophenacyl bromide (a specific sPLA2 inhibitor) but not by methylarachidonyl fluorophosphonate (a specific cytosolic type of PLA2). The X. nematophila culture broth contained PLA2 inhibitory factor(s), which was most abundant in the media obtained at a stationary bacterial growth phase. The PLA2 inhibitory factor(s) was heat-resistant and extracted in both aqueous and organic fractions. Effect of a PLA2-inhibitory fraction on the immunosuppression of T. castaneum was equally comparable with that resulted from inhibition of the TcPLA2 gene expression by RNA interference.

  • Identification of an Entomopathogenic Bacterium, Serratia sp. ANU101, and Its Hemolytic Activity
    Journal of microbiology and biotechnology, 2009
    Co-Authors: Yonggyun Kim, Sony Shrestha, Keunseob Kim, Ji-ae Seo, Hosanna H. Kim, Madanagopal Nalini
    Abstract:

    Four different bacterial colonies were isolated from an old stock of an Entomopathogenic nematode, Steinernema monticolum. They all showed Entomopathogenicity to final instar larvae of beet armyworm, Spodoptera exigua, by hemocoelic injection. However, they varied in colony form, susceptibility to antibiotics, and postmortem change of the infected host insects. Biolog microbial identification and 16S rDNA sequence analyses indicate that these are four different species classified into different bacterial genera. Owing to high Entomopathogenicity and a cadaver color of infected insect host, Serratia sp. was selected as a main symbiotic bacterial species and analyzed for its pathogenicity. Although no virulence of Serratia sp. was detected at oral administration, the bacteria gave significant synergistic pathogenicity to fifth instar S. exigua when it was treated along with a spore-forming Entomopathogenic Bacterium, Bacillus thuringiensis. The synergistic effect was explained by an immunosuppressive effect of Serratia sp. by its high cytotoxic effect on hemocytes of S. exigua, because Serratia sp. caused septicemia of S. exigua when the bacterial cells were injected into S. exigua hemocoel. The cytotoxic factor(s) was present in the culture medium because the sterilized culture broth possessed high potency in the cytotoxicity, which was specific to granular cells and plasmatocytes, two main immune-associated hemocytes in insects.

  • an Entomopathogenic Bacterium xenorhabdus nematophila inhibits hemocyte phagocytosis of spodoptera exigua by inhibiting phospholipase a2
    Journal of Invertebrate Pathology, 2007
    Co-Authors: Sony Shrestha
    Abstract:

    Abstract Phagocytosis is a hemocytic behavior against bacterial infection. An Entomopathogenic Bacterium, Xenorhabdus nematophila, inhibits immune responses of target insects and causes hemolymph septicemia. This study analyzed how X. nematophila could inhibit phagocytosis to increase its pathogenicity. Granular cells and plasmatocytes were the main phagocytic hemocytes of Spodoptera exigua determined by observing fluorescence-labeled bacteria in the cytosol. X. nematophila significantly inhibited phagocytosis of both hemocytes, while heat-killed X. nematophila lost its inhibitory potency. However, co-injection of X. nematophila with arachidonic acid did not show any significant inhibition of hemocyte phagocytosis. In fact, hemocytes of S. exigua infected with X. nematophila showed significant reduction in phospholipase A2 (PLA2) activity. Dexamethasone, a specific PLA2 inhibitor, significantly inhibited phagocytosis of both cell types. However, the inhibitory effect of dexamethasone was recovered by addition of arachidonic acid. Incubation of hemocytes with benzylideneacetone, a metabolite of X. nematophila, inhibited phagocytosis in a dose-dependent manner. These results suggest that X. nematophila produces and secretes PLA2 inhibitor(s), which in turn inhibit the phagocytic response of hemocytes.

Anna N. Kondakova - One of the best experts on this subject based on the ideXlab platform.