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

  • Molecular mechanism of polyketide shortening in anthraquinone biosynthesis of Photorhabdus luminescens
    Chemical science, 2019
    Co-Authors: Qiuqin Zhou, Alois Bräuer, Hélène Adihou, Maximilian Schmalhofer, Patricia Saura, Gina L. C. Grammbitter, Ville R. I. Kaila, Michael Groll, Helge B. Bode
    Abstract:

    Anthraquinones, a widely distributed class of aromatic natural products, are produced by a type II polyketide synthase system in the Gram-negative bacterium Photorhabdus luminescens. Heterologous expression of the antABCDEFGHI anthraquinone biosynthetic gene cluster in Escherichia coli identified AntI as an unusual lyase, catalysing terminal polyketide shortening prior to formation of the third aromatic ring. Functional in vitro and in vivo analysis of AntI using X-ray crystallography, structure-based mutagenesis, and molecular simulations revealed that AntI converts a defined octaketide to the tricyclic anthraquinone ring via retro-Claisen and Dieckmann reactions. Thus, AntI catalyses a so far unobserved multistep reaction in this PKS system.

  • insect specific production of new gamexpeptides in Photorhabdus luminescens tto1 widespread natural products in entomopathogenic bacteria
    ChemBioChem, 2015
    Co-Authors: Friederike I Nollmann, Carsten Kegler, Christina Dauth, Geraldine Mulley, Marcel Kaiser, Nicholas R Waterfield, Helge B. Bode
    Abstract:

    Discovery of new natural products by heterologous expression reaches its limits, especially when specific building blocks are missing in the heterologous host or the production medium. Here, we describe the insect-specific production of the new GameXPeptides E-H (5-8) from Photorhabdus luminescens TTO1, which can be produced heterologously from expression of the GameXPeptide synthetase GxpS only upon supplementation of the production media with the missing building blocks, and thus must be regarded as the true natural products under natural conditions.

  • Insect‐Specific Production of New GameXPeptides in Photorhabdus luminescens TTO1, Widespread Natural Products in Entomopathogenic Bacteria
    Chembiochem : a European journal of chemical biology, 2014
    Co-Authors: Friederike I Nollmann, Carsten Kegler, Christina Dauth, Geraldine Mulley, Marcel Kaiser, Nicholas R Waterfield, Helge B. Bode
    Abstract:

    Discovery of new natural products by heterologous expression reaches its limits, especially when specific building blocks are missing in the heterologous host or the production medium. Here, we describe the insect-specific production of the new GameXPeptides E-H (5-8) from Photorhabdus luminescens TTO1, which can be produced heterologously from expression of the GameXPeptide synthetase GxpS only upon supplementation of the production media with the missing building blocks, and thus must be regarded as the true natural products under natural conditions.

  • Triggering the production of the cryptic blue pigment indigoidine from Photorhabdus luminescens.
    Journal of biotechnology, 2011
    Co-Authors: Alexander O. Brachmann, Ferdinand Kirchner, Carsten Kegler, Sebastian C. Kinski, Imke Schmitt, Helge B. Bode
    Abstract:

    Abstract The production of the blue pigment indigoidine has been achieved in the entomopathogenic bacterium Photorhabdus luminescens by a promoter exchange and in Escherichia coli following heterologous expression of the biosynthesis gene indC . Moreover, genes involved in the regulation of this previously “silent” biosynthesis gene cluster have been identified in P. luminescens .

  • A type II polyketide synthase is responsible for anthraquinone biosynthesis in Photorhabdus luminescens.
    Chembiochem : a European journal of chemical biology, 2007
    Co-Authors: Alexander O. Brachmann, David Clarke, Susan A. Joyce, Holger Jenke-kodama, Gertrud Schwär, Helge B. Bode
    Abstract:

    Type II polyketide synthases are involved in the biosynthesis of numerous clinically relevant secondary metabolites with potent antibiotic or anticancer activity. Until recently the only known producers of type II PKSs were members of the Gram-positive actimomycetes, well-known producers of secondary metabolites in general. Here we present the second example of a type II PKS from Gram-negative bacteria. We have identified the biosynthesis gene cluster responsible for the production of anthraquinones (AQs) from the entomopathogenic bacterium Photorhabdus luminescens. This is the first example of AQ production in Gram-negative bacteria, and their heptaketide origin was confirmed by feeding experiments. Deletion of a cyclase/aromatase involved in AQ biosynthesis resulted in accumulation of mutactin and dehydromutactin, which have been described as shunt products of typical octaketide compounds from streptomycetes, and a pathway for AQ formation from octaketide intermediates is discussed.

Ralf Heermann - One of the best experts on this subject based on the ideXlab platform.

  • The Biocontrol Agent and Insect Pathogen Photorhabdus luminescens Interacts with Plant Roots
    Applied and environmental microbiology, 2020
    Co-Authors: Alice Regaiolo, Nazzareno Dominelli, Karsten Andresen, Ralf Heermann
    Abstract:

    ABSTRACT The number of sustainable agriculture techniques to improve pest management and environmental safety is rising, as biological control agents are used to enhance disease resistance and abiotic stress tolerance in crops. Here, we investigated the capacity of the Photorhabdus luminescens secondary variant to react to plant root exudates and their behavior toward microorganisms in the rhizosphere. P. luminescens is known to live in symbiosis with entomopathogenic nematodes (EPNs) and to be highly pathogenic toward insects. The P. luminescens-EPN relationship has been widely studied, and this combination has been used as a biological control agent; however, not much attention has been paid to the putative lifestyle of P. luminescens in the rhizosphere. We performed transcriptome analysis to show how P. luminescens responds to plant root exudates. The analysis highlighted genes involved in chitin degradation, biofilm regulation, formation of flagella, and type VI secretion system. Furthermore, we provide evidence that P. luminescens can inhibit growth of phytopathogenic fungi. Finally, we demonstrated a specific interaction of P. luminescens with plant roots. Understanding the role and the function of this bacterium in the rhizosphere might accelerate the progress in biocontrol manipulation and elucidate the peculiar mechanisms adopted by plant growth-promoting rhizobacteria in plant root interactions. IMPORTANCE Insect-pathogenic Photorhabdus luminescens bacteria are widely used in biocontrol strategies against pests. Very little is known about the life of these bacteria in the rhizosphere. Here, we show that P. luminescens can specifically react to and interact with plant roots. Understanding the adaptation of P. luminescens in the rhizosphere is highly important for the biotechnological application of entomopathogenic bacteria and could improve future sustainable pest management in agriculture.

  • Anti-Trypanosoma activity of bioactive metabolites from Photorhabdus luminescens and Xenorhabdus nematophila
    Experimental parasitology, 2019
    Co-Authors: Ana Maria Antonello, Ralf Heermann, Thaís Sartori, Matheus Brasil Da Silva, Josiane Somariva Prophiro, Phileno Pinge-filho, Onilda Santos Da Silva, Pedro R. T. Romão
    Abstract:

    Only two drugs are currently available for the treatment of Chagas disease and their effectiveness are unsatisfactory. Photorhabdus luminescens and Xenorhabdus nematophila, two enteric bacteria highly pathogenic to a broad range of insects, have been studied as potential source for bioactive metabolites against protozoa causing neglected tropical diseases. Therefore, we tested the in vitro anti-Trypanosoma cruzi activity of secreted metabolites from these bacteria. The conditioned medium of X. nematophila and P. luminescens showed significant parasiticidal activity in a concentration-dependent manner (IC50XN = 0.34 mg/mL, IC50PL = 1.0 mg/mL). The parasiticidal compound was identified as a small molecule stable to heating and pH changes ranging from 2 to 12. Moreover, anti-Trypanosoma molecules secreted by both bacteria stimulate the trypanocidal activity of macrophages by a mechanism independent of nitric oxide. Summarizing, our studies reveal that P. luminescens and X. nematophila are potential sources of putative novel drugs against Chagas disease.

  • Phenotypic and genomic comparison of Photorhabdus luminescens subsp. laumondii TT01 and a widely used rifampicin-resistant Photorhabdus luminescens laboratory strain.
    BMC genomics, 2018
    Co-Authors: Maria-antonia Zamora-lagos, Simone Eckstein, Angela Langer, Athanasios Gazanis, Friedhelm Pfeiffer, Bianca Habermann, Ralf Heermann
    Abstract:

    Background Photorhabdus luminescens is an enteric bacterium, which lives in mutualistic association with soil nematodes and is highly pathogenic for a broad spectrum of insects. A complete genome sequence for the type strain P. luminescens subsp. laumondii TT01, which was originally isolated in Trinidad and Tobago, has been described earlier. Subsequently, a rifampicin resistant P. luminescens strain has been generated with superior possibilities for experimental characterization. This strain, which is widely used in research, was described as a spontaneous rifampicin resistant mutant of TT01 and is known as TT01-RifR.

  • Entomopathogenic bacteria Photorhabdus luminescens as drug source against Leishmania amazonensis.
    Parasitology, 2017
    Co-Authors: Ana Maria Antonello, Ralf Heermann, Thaís Sartori, Pedro R. T. Romão, Ana Paula Folmer Correa, Adriano Brandelli, Luiz Carlos Rodrigues Junior, Alessandra Peres, Onilda Santos Da Silva
    Abstract:

    Leishmaniasis is a widely spread and zoonotic disease with serious problems as low effectiveness of drugs, emergence of parasite resistance and severe adverse reactions. In recent years, considerable attention has been given to secondary metabolites produced by Photorhabdus luminescens, an entomopathogenic bacterium. Here, we assessed the leishmanicidal activity of P. luminescens culture fluids. Initially, promastigotes of Leishmania amazonensis were incubated with cell free conditioned medium of P. luminescens and parasite survival was monitored. Different pre-treatments of the conditioned medium revealed that the leishmanicidal activity is due to a secreted peptide smaller than 3 kDa. The Photorhabdus-derived leishmanicidal toxin (PLT) was enriched from conditioned medium and its effect on mitochondrial membrane potential of promastigotes, was determined. Moreover, the biological activity of PLT against amastigotes was evaluated. PLT inhibited the parasite growth and showed significant leishmanicidal activity against promastigote and amastigotes of L. amazonensis. PLT also caused mitochondrial dysfunction in parasites, but low toxicity to mammalian cell and human erythrocytes. Moreover, the anti-amastigote activity was independent of nitric oxide production. In summary, our results highlight that P. luminescens secretes Leishmania-toxic peptide(s) that are promising novel drugs for therapy against leishmaniasis.

Friederike I Nollmann - One of the best experts on this subject based on the ideXlab platform.

Ralf-udo Ehlers - One of the best experts on this subject based on the ideXlab platform.

  • Photorhabdus luminescens LN2 requires rpoS for nematicidal activity and nematode development.
    FEMS microbiology letters, 2016
    Co-Authors: Xuehong Qiu, Ralf-udo Ehlers, Li Cao, Richou Han
    Abstract:

    Photorhabdus (Enterobacteriaceae) bacteria are pathogenic to insects and mutualistic with entomopathogenic Heterorhabditis nematodes . Photorhabdus luminescens subsp. akhurstii LN2, associated with Heterorhabditis indica LN2, shows nematicidal activity against H. bacteriophora H06 infective juveniles (IJs). In the present study, an rpoS mutant of P. luminescens LN2 was generated through allelic exchange to examine the effects of rpoS deletion on the nematicidal activity and nematode development. The results showed that P. luminescens LN2 required rpoS for nematicidal activity against H06 nematodes, normal IJ recovery and development of H. indica LN2, however, not for the bacterial colonization in LN2 and H06 IJs. This provides cues for further understanding the role of rpoS in the mutualistic association between entomopathogenic nematodes and their symbionts.

  • two new subspecies of Photorhabdus luminescens isolated from heterorhabditis bacteriophora nematoda heterorhabditidae Photorhabdus luminescens subsp kayaii subsp nov and Photorhabdus luminescens subsp thracensis subsp nov
    Systematic and Applied Microbiology, 2004
    Co-Authors: Selcuk Hazir, Ralf-udo Ehlers, Erko Stackebrandt, Elke Lang, Peter Schumann, Nevin Keskin
    Abstract:

    Summary Bacterial isolates from nematodes from Turkish soil samples were initially characterized by molecular methods and seven members of the genus Photorhabdus identified to the species level, using riboprint analyses and metabolic properties. Strain 07-5 (DSM 15195) was highly related to the type strain of Photorhabdus luminescens subsp. laumondii DSM 15139 T , and was regarded a strain of this subspecies. Strains 1121 T (DSM 15194 T ), 68-3 (DSM 15198) and 47-10 (DSM 15197) formed one, strain 39-8 T (DSM 15199 T ), 39-7 (DSM 15196) and 01-12 (DSM 15193) formed a second cluster that branched intermediate the three subspecies of Photorhabdus luminescens . Based upon moderate 16S rRNA gene sequence similarities and differences in metabolic properties among themselves and with type strains of the three subspecies we consider the two clusters to represent two new subspecies of Photorhabdus luminescens for which the names Photorhabdus luminescens subsp. kayaii , type strain 1121 T (DSM 15194 T , NCIMB 13951 T ), and Photorhabdus luminescens subsp. thracensis subsp. nov., type strain 39-8 T (DSM 15199 T , NCIMB 13952 T ) are proposed.

  • Growth of Photorhabdus luminescens in batch and glucose fed-batch culture.
    Applied microbiology and biotechnology, 2000
    Co-Authors: T. Jeffke, Ralf-udo Ehlers, D. Jende, C. Mätje, L. Berthe-corti
    Abstract:

    Photorhabdus luminescens, a bacterial symbiont of entomopathogenic biocontrol nematodes, was grown in batch and glucose fed-batch culture. The cell density, bioluminescence, production of antibiotic substances, number of cells with inclusion bodies, glucose concentration and oxygen uptake rate were recorded. The addition of 12.4 g l−1 glucose prolonged the growth, and the yield almost doubled, from 6.85 g l−1 to 12.45 g l−1 dry mass. The production of antibiotic substances increased by 140%. Bioluminescence was higher in the batch culture. A shift of P. luminescens to phase II variants was not detected.

  • Mass Production Potential of the Bacto-Helminthic Biocontrol Complex Heterorhabditis indica - Photorhabdus luminescens
    Biocontrol Science and Technology, 2000
    Co-Authors: Ralf-udo Ehlers, D. Jende, I. Niemann, S. Hollmer, Olaf Strauch, M. Shanmugasundaram, U. K. Mehta, S. K. Easwaramoorthy, Ann M. Burnell
    Abstract:

    Heterorhabditis indica is a potential agent for the biological control of grubs in sugarcane fields in India. The type strain LN 2 was transferred to monoxenic cultures on its symbiont Photorhabdus luminescens and successfully produced on solid media. In liquid cultures, a mean dauer juvenile yield of 457 000 was obtained with a maximum of 648 000 per ml. Comparatively high yields have not been reported before. Therefore, costs related to the liquid culture production of H. indica will be lower than for other entomopathogenic nematodes currently used in biocontrol. Different bacterial clones had no significant influence on the dauer juvenile yields in liquid media. The exit from the dauer juvenile stage (recovery) after inoculation and the number of hermaphrodites significantly decreased when culture temperature was increased from 25-30 ° C; the dauer juvenile yields were not affected. The cell density of P. luminescens in batch cultures was higher at 25 and 30 ° C than at growth temperatures of...

  • Trans-specific nematicidal activity of Photorhabdus luminescens
    Nematology, 1999
    Co-Authors: Richou Han, Ralf-udo Ehlers
    Abstract:

    Mixed culture filtrates of Photorhabdus luminescens isolated from Heterorhabditis bacteriophora H06 and from H. indica LN2 had a toxic effect on axenic H. bacteriophora H06 dauer juveniles. Single culture filtrates had no effect. When one filtrate originated from a secondary phase culture, the toxic effect was lost. Heat treatment of one of the filtrates to 80°C destroyed the effect. The toxin is probably synthesized de novo after mixing the culture supernatants of these two P. luminescens symbionts. Dilution of the filtrate reduced the effect, and it was lost when P. luminescens was cultured for more than two days. Steinernema carpocapsae A24 was not affected by the mixture, and was affected only by the filtrate of primary phase P. luminescens H06. The toxic effect was recorded also when axenic dauer juveniles of H. bacteriophora were inoculated into a mixed bacterial culture of H06 and LN2. Inoculating monoxenic dauer juveniles of H. bacteriophora H06 into P. luminescens LN2 or into mixtures containing LN2 bacteria resulted in significant dauer juvenile mortality. These manifestations of the interaction of bacteria to produce toxic effects on the non-symbiotic nematode (trans-specific activity) may have an impact on competitive interactions when one insect host is infected by different nematode species. Eine transspezifische nematizide Aktivitat von Photorhabdus luminescens - Eine Mischung der Kulturfiltrate des Bakteriums Photorhabdus luminescens, isoliert aus Heterorhabditis bacteriophora H06 mit dem Filtrat des Symbionten aus H. indica LN2 wirkt toxisch auf axenische Dauerlarven von H. bacteriophora H06. Die einzelnen Kulturfiltrate zeigten keine Wirkung. Sofern ein Filtrat einer Sekundarformkultur entnommen wurde, konnte kein Effekt erzielt werden. Eine Hitzebehandlung bei 80°C zerstorte die Wirkung. Das Toxin wird wahrscheinlich de novo synthetisiert in dem Moment, in dem die Kulturfiltrate dieser P. luminescens Symbionten gemischt werden. Eine Verdunnung der Filtrate reduzierte die Wirkung. Sie ging ganz verloren, wenn P. luminescens langer als zwei Tage kultiviert wurde. Die Mischung hatte keine Wirkung auf axenische Steinernema carpocapsae. Dieser Nematode wurde nur durch Filtrate der Primarform von P. luminescens H06 abgetotet. Die toxischen Effekte wurden auch festgestellt, wenn axenische Dauerlarven von H. bacteriophora in Gemische von H06 und LN2 Bakterienkulturen inokuliert wurde. Bei Inokulation von monoxenischen Dauerlarven von H. bacteriophora H06 in P. luminescens LN2 oder in Gemische, die LN2 enthielten, wurde ebenfalls eine gesteigerte Mortalitat festgestellt. Dieses Deutlichwerden von Wechselbeziehungen zwischen den Bakterien bei Erzeugung toxischer Effekte auf den nicht-symbiontischen Nematoden (trans-spezifische Aktivitat) konnte eine Auswirkung auf die Konkurrenz bei Koinfektion eines Wirtsinsekts mit zwei Nematodenarten haben.

Klaus Aktories - One of the best experts on this subject based on the ideXlab platform.

  • Involvement of N-glycans in binding of Photorhabdus luminescens Tc toxin.
    Cellular microbiology, 2021
    Co-Authors: Peter Njenga Ng’ang’a, Alexander E Lang, Klaus Aktories, Lina Siukstaite, Hans Bakker, Winfried Römer, Gudula Schmidt
    Abstract:

    Photorhabdus luminescens Tc toxins are large tripartite ABC-type toxin complexes, composed of TcA, TcB and TcC proteins. Tc toxins are widespread and have shown a tropism for a variety of targets including insect, mammalian and human cells. However, their receptors and the specific mechanisms of uptake into target cells remain unknown. Here, we show that the TcA protein TcdA1 interacts with N-glycans, particularly Lewis X/Y antigens. This is confirmed using N-acetylglucosamine transferase I (Mgat1 gene product)-deficient Chinese hamster ovary (CHO) Lec1 cells, which are highly resistant to intoxication by the Tc toxin complex most likely due to the absence of complex N-glycans. Restoring Mgat1 gene activity, and hence complex N-glycan biosynthesis, recapitulated the sensitivity of these cells to the toxin. Exogenous addition of Lewis X trisaccharide partially inhibits intoxication in wild-type cells. Additionally, sialic acid also largely reduced binding of the Tc toxin. Moreover, proteolytic activation of TcdA1 alters glycan-binding and uptake into target cells. The data suggest that TcdA1-binding is most likely multivalent, and carbohydrates probably work cooperatively to facilitate binding and intoxication.

  • Engineering Photorhabdus luminescens toxin complex (PTC) into a recombinant injection nanomachine.
    Life science alliance, 2019
    Co-Authors: Peter Njenga Ng´ang´a, Klaus Aktories, Julia K. Ebner, Matthias Plessner, Gudula Schmidt
    Abstract:

    Engineering delivery systems for proteins and peptides into mammalian cells is an ongoing challenge for cell biological studies as well as for therapeutic approaches. Photorhabdus luminescens toxin complex (PTC) is a heterotrimeric protein complex able to deliver diverse protein toxins into mammalian cells. We engineered the syringe-like nanomachine for delivery of protein toxins from different species. In addition, we loaded the highly active copepod luciferase Metridia longa M-Luc7 for accurate quantification of injected molecules. We suggest that besides the probable size limitation, the charge of the cargo also influences the efficiency of packing and transport into mammalian cells. Our data show that the PTC constitutes a powerful system to inject recombinant proteins, peptides, and potentially, other molecules into mammalian cells. In addition, in contrast to other protein transporters based on pore formation, the closed, compact structure of the PTC may protect cargo from degradation.

  • Photorhabdus luminescens Toxin complex (TCC) a recombinant injection nano-machine - delivery of recombinant Yersinia enterocolitica YopT
    2019
    Co-Authors: Gudula Schmidt, Klaus Aktories, Peter Njenga Ng’ang’a, Julia K. Ebner, Matthias Plessner
    Abstract:

    ABSTRACT Engineering delivery systems for proteins and peptides into mammalian cells is an ongoing challenge for cell biological studies as well as for therapeutic approaches. Photorhabdus luminescens toxin complex (PTC) is a heterotrimeric protein complex able to deliver diverse protein toxins into mammalian cells. We engineered the syringe like nano-machine for delivery of protein toxins from different species. Additionally, we loaded the highly active copepod luciferase Metridia longa M-Luc7 for accurate quantification of injected molecules. We suggest that besides the size also the charge of the cargo defines the efficiency of packing and transport into mammalian cells. Our data show that the Photorhabdus luminescens toxin complex constitutes a powerful system to inject recombinant proteins, peptides and potentially other molecules like aptamers into mammalian cells. In contrast to other protein transporters based on pore formation, the cargo is protected from degradation. The system opens new perspectives for cell research and pharmacology.

  • Photorhabdus luminescens toxins TccC3 and TccC5: insecticidal ADP-ribosyltransferases that modify threonine and glutamine.
    Current topics in microbiology and immunology, 2014
    Co-Authors: Klaus Aktories, Gudula Schmidt, Alexander E Lang
    Abstract:

    The ADP-ribosyltransferases TccC3 and TccC5 are the biologically active TcC components of the tripartite Photorhabdus luminescens Tc toxin, which consist of TcA, TcB, and TcC components. TcA is the binding and membrane translocation component. TcB is a functional linker between TcC and TcA and also involved in the translocation of the toxin. While TccC3 ADP-ribosylates actin at threonine 148, TccC5 modifies Rho proteins at glutamine 61/63. Both modifications result in major alteration of the actin cytoskeleton. Here we discuss structure and function of the Tc toxin and compare its ADP-ribosyltransferase activities with other types of actin and Rho modifying toxins.

  • a syringe like injection mechanism in Photorhabdus luminescens toxins
    Nature, 2013
    Co-Authors: Christos Gatsogiannis, Alexander E Lang, D Meusch, Vanda Pfaumann, Oliver Hofnagel, Roland Benz, Klaus Aktories, Stefan Raunser
    Abstract:

    The TcA component of Photorhabdus luminescens ABC-type toxin complexes forms a transmembrane pore and injects TcC, the functional component of the toxin, into the target cell by means of a syringe-like mechanism.