Chemical language and warfare of bacterial natural products in bacteria-nematode-insect interactions.

Covering: up to November 2017 Organismic interaction is one of the fundamental principles for survival in any ecosystem. Today, numerous examples show the interaction between microorganisms like bacteria and higher eukaryotes that can be anything between mutualistic to parasitic/pathogenic symbioses. There is also increasing evidence that microorganisms are used by higher eukaryotes not only for the supply of essential factors like vitamins but also as biological weapons to protect themselves or to kill other organisms. Excellent examples for such systems are entomopathogenic nematodes of the genera Heterorhabditis and Steinernema that live in mutualistic symbiosis with bacteria of the genera Photorhabdus and Xenorhabdus, respectively. Although these systems have been used successfully in organic farming on an industrial scale, it was only shown during the last 15 years that several different natural products (NPs) produced by the bacteria play key roles in the complex life cycle of the bacterial symbionts, the nematode host and the insect prey that is killed by and provides nutrients for the nematode-bacteria pair. Since the bacteria can switch from mutualistic to pathogenic lifestyle, interacting with two different types of higher eukaryotes, and since the full system with all players can be established in the lab, they are promising model systems to elucidate the natural function of microbial NPs. This review summarizes the current knowledge as well as open questions for NPs from Photorhabdus and Xenorhabdus and tries to assign their roles in the tritrophic relationship.

[1]  Morgan A. Wyatt,et al.  Heterologous Expression and Structural Characterisation of a Pyrazinone Natural Product Assembly Line , 2012, Chembiochem : a European journal of chemical biology.

[2]  R. Heermann,et al.  Specificity of Signal-Binding via Non-AHL LuxR-Type Receptors , 2015, PloS one.

[3]  J. Crawford,et al.  Activating and Attenuating the Amicoumacin Antibiotics , 2016, Molecules.

[4]  Qiuqin Zhou,et al.  Simple “On‐Demand” Production of Bioactive Natural Products , 2015, Chembiochem : a European journal of chemical biology.

[5]  H. Adihou,et al.  Biosynthesis of the Antibiotic Nematophin and Its Elongated Derivatives in Entomopathogenic Bacteria. , 2017, Organic letters.

[6]  H. Bode,et al.  Reciprocal cross talk between fatty acid and antibiotic biosynthesis in a nematode symbiont. , 2012, Angewandte Chemie.

[7]  T. Schmeing,et al.  Structural and functional aspects of the nonribosomal peptide synthetase condensation domain superfamily: discovery, dissection and diversity. , 2017, Biochimica et biophysica acta. Proteins and proteomics.

[8]  L. Bigler,et al.  Heterologous expression of a Photorhabdus luminescens syrbactin-like gene cluster results in production of the potent proteasome inhibitor glidobactin A. , 2013, Microbiological research.

[9]  M. Kurz,et al.  Fabclavines: Bioactive Peptide–Polyketide‐Polyamino Hybrids from Xenorhabdus , 2014, Chembiochem : a European journal of chemical biology.

[10]  R. Ehlers,et al.  Pathogenicity, development, and reproduction of Heterorhabditis bacteriophora and Steinernema carpocapsae under axenic in vivo conditions. , 2000, Journal of invertebrate pathology.

[11]  C. Allen,et al.  Ralfuranone biosynthesis in Ralstonia solanacearum suggests functional divergence in the quinone synthetase family of enzymes. , 2011, Chemistry & biology.

[12]  H. Bode,et al.  Genome comparisons provide insights into the role of secondary metabolites in the pathogenic phase of the Photorhabdus life cycle , 2016, BMC Genomics.

[13]  C. Walsh,et al.  Dithiolopyrrolones: biosynthesis, synthesis, and activity of a unique class of disulfide-containing antibiotics. , 2014, Natural product reports.

[14]  J. Carney,et al.  Photobactin: a Catechol Siderophore Produced by Photorhabdus luminescens, an Entomopathogen Mutually Associated with Heterorhabditis bacteriophora NC1 Nematodes , 2003, Applied and Environmental Microbiology.

[15]  J. Clardy,et al.  Cloning and heterologous expression of isocyanide biosynthetic genes from environmental DNA. , 2005, Angewandte Chemie.

[16]  G. F. White A METHOD FOR OBTAINING INFECTIVE NEMATODE LARVAE FROM CULTURES. , 1927, Science.

[17]  R. Akhurst,et al.  A numerical taxonomic study of the genus Xenorhabdus (Enterobacteriaceae) and proposed elevation of the subspecies of X. nematophilus to species. , 1988, Journal of general microbiology.

[18]  H. Bode,et al.  Bioactive natural products from novel microbial sources , 2015, Annals of the New York Academy of Sciences.

[19]  M. Lacey,et al.  Biologically active metabolites from Xenorhabdus spp., Part 2. Benzopyran-1-one derivatives with gastroprotective activity. , 1991, Journal of natural products.

[20]  E. Dittmann,et al.  Aurachin‐Biosynthese im Gram‐negativen Bakterium Stigmatella aurantiaca: Beteiligung einer Typ‐II‐Polyketidsynthase , 2007 .

[21]  H. Bode,et al.  Xenortide Biosynthesis by Entomopathogenic Xenorhabdus nematophila. , 2014, Journal of natural products.

[22]  H. Bode Entomopathogenic bacteria as a source of secondary metabolites. , 2009, Current opinion in chemical biology.

[23]  Jianxiong Li,et al.  Antibiotics fromXenorhabdus spp. andPhotorhabdus spp. (Enterobacteriaceae) (review) , 1998 .

[24]  Lian-Hui Zhang,et al.  SlyA regulates phytotoxin production and virulence in Dickeya zeae EC1. , 2016, Molecular plant pathology.

[25]  Tilmann Weber,et al.  Characterization of the ‘pristinamycin supercluster’ of Streptomyces pristinaespiralis , 2011, Microbial biotechnology.

[26]  Michael G Thomas,et al.  Characterization of the Complete Zwittermicin A Biosynthesis Gene Cluster from Bacillus cereus , 2008, Applied and Environmental Microbiology.

[27]  R. Ueoka,et al.  Colibactin biosynthesis and biological activity depend on the rare aminomalonyl polyketide precursor. , 2015, Chemical communications.

[28]  J. Crawford,et al.  Lumiquinone A, an α-Aminomalonate-Derived Aminobenzoquinone from Photorhabdus luminescens. , 2015, Journal of natural products.

[29]  D. Clarke,et al.  Photorhabdus and a host of hosts. , 2009, Annual review of microbiology.

[30]  M. Karas,et al.  Neutral loss fragmentation pattern based screening for arginine-rich natural products in Xenorhabdus and Photorhabdus. , 2012, Analytical chemistry.

[31]  S. Pongor,et al.  Census of solo LuxR genes in prokaryotic genomes , 2015, Frontiers in Cellular and Infection Microbiology.

[32]  H. Bode,et al.  Bacterial biosynthesis of a multipotent stilbene. , 2008, Angewandte Chemie.

[33]  I. Abe,et al.  Structural Insight into the Enzymatic Formation of Bacterial Stilbene. , 2016, Cell chemical biology.

[34]  E. Rosenberg,et al.  Microbes Drive Evolution of Animals and Plants: the Hologenome Concept , 2016, mBio.

[35]  J. Gerrard,et al.  A Review of Clinical Cases of Infection with Photorhabdus Asymbiotica. , 2017, Current topics in microbiology and immunology.

[36]  R. U. Ehlers,et al.  Regulation of biological control agents , 2011 .

[37]  Philip Rosenstiel,et al.  The native microbiome of the nematode Caenorhabditis elegans: gateway to a new host-microbiome model , 2016, BMC Biology.

[38]  R. Heermann,et al.  Languages and dialects: bacterial communication beyond homoserine lactones. , 2015, Trends in microbiology.

[39]  S. Gilbert,et al.  Getting the Hologenome Concept Right: an Eco-Evolutionary Framework for Hosts and Their Microbiomes , 2016, mSystems.

[40]  H. Bode,et al.  Genetic analysis of xenocoumacin antibiotic production in the mutualistic bacterium Xenorhabdus nematophila , 2009, Molecular microbiology.

[41]  R. Heermann,et al.  Pyrones as bacterial signaling molecules. , 2013, Nature chemical biology.

[42]  D. Steinhilber,et al.  Characterisation of taxlllaids A-G; natural products from Xenorhabdus indica. , 2014, Chemistry.

[43]  Michael Karas,et al.  Structure elucidation and biosynthesis of lysine-rich cyclic peptides in Xenorhabdus nematophila. , 2011, Organic & biomolecular chemistry.

[44]  R. Akhurst Morphological and Functional Dimorphism in Xenorhabdus spp., Bacteria Symbiotically Associated with the Insect Pathogenic Nematodes Neoaplectana and Heterorhabditis , 1980 .

[45]  Qiuqin Zhou,et al.  Natural Products from Photorhabdus and Other Entomopathogenic Bacteria. , 2017, Current topics in microbiology and immunology.

[46]  H. Stark,et al.  From a Multipotent Stilbene to Soluble Epoxide Hydrolase Inhibitors with Antiproliferative Properties , 2013, ChemMedChem.

[47]  E. Czyzewska,et al.  Antimicrobial metabolites from a bacterial symbiont. , 1995, Journal of natural products.

[48]  R. Akhurst,et al.  Biochemical and Physiological Characterization of Colony Form Variants in Xenorhabdus spp. (Enterobacteriaceae) , 1988 .

[49]  H. Bode,et al.  Yeast Homologous Recombination Cloning Leading to the Novel Peptides Ambactin and Xenolindicin , 2014, Chembiochem : a European journal of chemical biology.

[50]  H. Bode,et al.  Identification and occurrence of the hydroxamate siderophores aerobactin, putrebactin, avaroferrin and ochrobactin C as virulence factors from entomopathogenic bacteria , 2017, Environmental microbiology.

[51]  I. Abe,et al.  Novel polyketides synthesized with a higher plant stilbene synthase. , 2001, European journal of biochemistry.

[52]  R. Frutos,et al.  Insect pathogens as biological control agents: Back to the future. , 2015, Journal of invertebrate pathology.

[53]  K. Theis,et al.  Host Biology in Light of the Microbiome: Ten Principles of Holobionts and Hologenomes , 2015, PLoS biology.

[54]  R. Cox,et al.  13C labeling reveals multiple amination reactions in the biosynthesis of a novel polyketide polyamine antibiotic zeamine from Dickeya zeae. , 2010, Chemical communications.

[55]  M. Kaiser,et al.  One-shot NMR analysis of microbial secretions identifies highly potent proteasome inhibitor , 2012, Proceedings of the National Academy of Sciences.

[56]  H. Bode,et al.  Entomopathogenic bacteria use multiple mechanisms for bioactive peptide library design. , 2017, Nature chemistry.

[57]  A. Givaudan,et al.  Plastic architecture of bacterial genome revealed by comparative genomics of Photorhabdus variants , 2008, Genome Biology.

[58]  K. Nealson,et al.  Growth and luminescence of the symbolic bacteria associated with the terrestrial nematode, Heterorphabditis bacteriophora , 1980 .

[59]  A. Horswill,et al.  A Phosphopantetheinyl Transferase Homolog Is Essential for Photorhabdus luminescens To Support Growth and Reproduction of the Entomopathogenic NematodeHeterorhabditis bacteriophora , 2001, Journal of bacteriology.

[60]  F. Chang,et al.  Antimicrobial activity and biosynthesis of indole antibiotics produced by Xenorhabdus nematophilus. , 1993, Journal of general microbiology.

[61]  W. Richardson,et al.  Identification of an anthraquinone pigment and a hydroxystilbene antibiotic from Xenorhabdus luminescens , 1988, Applied and environmental microbiology.

[62]  Mark L. Blaxter,et al.  Second-generation environmental sequencing unmasks marine metazoan biodiversity , 2010, Nature communications.

[63]  G. Poinar,et al.  History of entomopathogenic nematology. , 2012, Journal of nematology.

[64]  J. Nougayrède,et al.  ClbP Is a Prototype of a Peptidase Subgroup Involved in Biosynthesis of Nonribosomal Peptides* , 2011, The Journal of Biological Chemistry.

[65]  Ralph A. Cacho,et al.  Structural basis of nonribosomal peptide macrocyclization in fungi. , 2016, Nature chemical biology.

[66]  Todd A. Ciche The biology and genome of Heterorhabditis bacteriophora. , 2007, WormBook : the online review of C. elegans biology.

[67]  L. Gerritsen,et al.  Characterization of form variants of Xenorhabdus luminescens , 1992, Applied and environmental microbiology.

[68]  D. Clarke The Regulation of Secondary Metabolism in Photorhabdus. , 2016, Current topics in microbiology and immunology.

[69]  J. Imhoff,et al.  Linear and cyclic peptides from the entomopathogenic bacterium Xenorhabdus nematophilus. , 2008, Journal of natural products.

[70]  R. Ehlers,et al.  Dangerous liaisons: The symbiosis of entomopathogenic nematodes and bacteria , 2006 .

[71]  E. Proschak,et al.  Biosynthesis of the Insecticidal Xenocyloins in Xenorhabdus bovienii , 2014, Chembiochem : a European journal of chemical biology.

[72]  Josephine E E U Hellberg,et al.  The broad-spectrum antibiotic, zeamine, kills the nematode worm Caenorhabditis elegans , 2015, Front. Microbiol..

[73]  Ingo Ebersberger,et al.  Natural product diversity associated with the nematode symbionts Photorhabdus and Xenorhabdus , 2017, Nature Microbiology.

[74]  H. Bode,et al.  A New Type of Pyrrolidine Biosynthesis Is Involved in the Late Steps of Xenocoumacin Production in Xenorhabdus nematophila , 2009, Chembiochem : a European journal of chemical biology.

[75]  N. Waterfield,et al.  Photorhabdus asymbiotica as an Insect and Human Pathogen. , 2016, Current topics in microbiology and immunology.

[76]  W. Thomas,et al.  D. Baines,et al.  Octopamine enhances phagocytosis in cockroach hemocytes: involvement of inositol trisphosphate. , 1994, Archives of insect biochemistry and physiology.

[78]  H. Bode,et al.  Xenofuranones A and B: phenylpyruvate dimers from Xenorhabdus szentirmaii. , 2006, Journal of natural products.

[79]  Chad W. Johnston,et al.  Nonribosomal Assembly of Natural Lipocyclocarbamate Lipoprotein‐Associated Phospholipase Inhibitors , 2013, Chembiochem : a European journal of chemical biology.

[80]  R. Fischer,et al.  Histone acetylation mediates epigenetic regulation of transcriptional reprogramming in insects during metamorphosis, wounding and infection , 2012, Frontiers in Zoology.

[81]  J. Ensign,et al.  Purification and Characterization of a High-Molecular-Weight Insecticidal Protein Complex Produced by the Entomopathogenic BacteriumPhotorhabdus luminescens , 1998, Applied and Environmental Microbiology.

[82]  H. Bode,et al.  Insect‐Specific Production of New GameXPeptides in Photorhabdus luminescens TTO1, Widespread Natural Products in Entomopathogenic Bacteria , 2015, Chembiochem : a European journal of chemical biology.

[83]  C. Ottmann,et al.  The chemistry and biology of syringolins, glidobactins and cepafungins (syrbactins). , 2011, Natural product reports.

[84]  D. Stanley,et al.  Eicosanoid Actions in Insect Immunity , 2009, Journal of Innate Immunity.

[85]  B. Shen,et al.  C-O Bond Formation by Polyketide Synthases , 2002, Science.

[86]  R. Poulin,et al.  Biological warfare: Microorganisms as drivers of host-parasite interactions. , 2015, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[87]  J. Webster,et al.  Nematicidal metabolites produced by Photorhabdus luminescens (Enterobacteriaceae), bacterial symbiont of entomopathogenic nematodes , 1999 .

[88]  A. Aertsen,et al.  A PKS/NRPS/FAS Hybrid Gene Cluster from Serratia plymuthica RVH1 Encoding the Biosynthesis of Three Broad Spectrum, Zeamine-Related Antibiotics , 2013, PloS one.

[89]  A. Knoll,et al.  Animals in a bacterial world, a new imperative for the life sciences , 2013, Proceedings of the National Academy of Sciences.

[90]  H. Overkleeft,et al.  Paenilamicin: structure and biosynthesis of a hybrid nonribosomal peptide/polyketide antibiotic from the bee pathogen Paenibacillus larvae. , 2014, Angewandte Chemie.

[91]  Yonggyun Kim,et al.  An entomopathogenic bacterium, Xenorhabdus nematophila, inhibits hemocyte phagocytosis of Spodoptera exigua by inhibiting phospholipase A(2). , 2007, Journal of invertebrate pathology.

[92]  Bonnie L. Bassler,et al.  Quorum sensing signal–response systems in Gram-negative bacteria , 2016, Nature Reviews Microbiology.

[93]  R. Heermann,et al.  Dialkylresorcinols as bacterial signaling molecules , 2014, Proceedings of the National Academy of Sciences.

[94]  J. Webster,et al.  Nematophin, a novel antimicrobial substance produced by Xenorhabdus nematophilus (Enterobactereaceae). , 1997, Canadian journal of microbiology.

[95]  K. Frankenhuyzen Insecticidal activity of Bacillus thuringiensis crystal proteins , 2009 .

[96]  Bingbing Li,et al.  Two symbiotic bacteria of the entomopathogenic nematode Heterorhabditis spp. against Galleria mellonella , 2017, Toxicon.

[97]  Kristian Fog Nielsen,et al.  Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking , 2016, Nature Biotechnology.

[98]  Yonggyun Kim,et al.  Phospholipase A2 Inhibitors Synthesized by Two Entomopathogenic Bacteria, Xenorhabdus nematophila and Photorhabdus temperata subsp. temperata , 2012, Applied and Environmental Microbiology.

[99]  C. Walsh,et al.  Cyclization of Fungal Nonribosomal Peptides by a Terminal Condensation-Like Domain , 2012, Nature chemical biology.

[100]  M. Galbraith,et al.  The Terminal Aminoguanidine Chain of Phleo-mycin G , 1979 .

[101]  A. Kisselev Joining the army of proteasome inhibitors. , 2008, Chemistry & biology.

[102]  I. Schmitt,et al.  Triggering the production of the cryptic blue pigment indigoidine from Photorhabdus luminescens. , 2012, Journal of biotechnology.

[103]  L. Bigler,et al.  Identification of genes involved in the biosynthesis of the cytotoxic compound glidobactin from a soil bacterium. , 2007, Environmental microbiology.

[104]  K. Zangger,et al.  Biosynthesis of the Enterotoxic Pyrrolobenzodiazepine Natural Product Tilivalline , 2017, Angewandte Chemie.

[105]  A. Aertsen,et al.  The Zeamine Antibiotics Affect the Integrity of Bacterial Membranes , 2014, Applied and Environmental Microbiology.

[106]  H. Bode,et al.  Rapid Determination of the Amino Acid Configuration of Xenotetrapeptide , 2014, Chembiochem : a European journal of chemical biology.

[107]  H. Blöcker,et al.  The myxochelin iron transport regulon of the myxobacterium Stigmatella aurantiaca Sg a15. , 2000, European journal of biochemistry.

[108]  J. Segre,et al.  Signaling in Host-Associated Microbial Communities , 2016, Cell.

[109]  Yonggyun Kim,et al.  Octopamine and 5-hydroxytryptamine mediate hemocytic phagocytosis and nodule formation via eicosanoids in the beet armyworm, Spodoptera exigua. , 2009, Archives of insect biochemistry and physiology.

[110]  D. Clarke,et al.  HdfR is a regulator in Photorhabdus luminescens that modulates metabolism and symbiosis with the nematode Heterorhabditis. , 2012, Environmental microbiology.

[111]  D. Clarke,et al.  The Regulation of Secondary Metabolism and Mutualism in the Insect Pathogenic Bacterium Photorhabdus luminescens. , 2011, Advances in applied microbiology.

[112]  R. Akhurst Antibiotic activity of Xenorhabdus spp., bacteria symbiotically associated with insect pathogenic nematodes of the families Heterorhabditidae and Steinernematidae. , 1982, Journal of general microbiology.

[113]  A. Batzer,et al.  Structure determination of the bioactive depsipeptide xenobactin from Xenorhabdus sp. PB30.3 , 2013 .

[114]  Karl W Barber,et al.  Genome mining unearths a hybrid nonribosomal peptide synthetase-like-pteridine synthase biosynthetic gene cluster , 2017, eLife.

[115]  Nuno Bandeira,et al.  Mass spectral molecular networking of living microbial colonies , 2012, Proceedings of the National Academy of Sciences.

[116]  J. Crawford,et al.  Exploiting a global regulator for small molecule discovery in Photorhabdus luminescens. , 2010, ACS chemical biology.

[117]  H. Bode,et al.  Formation of 1,3-cyclohexanediones and resorcinols catalyzed by a widely occurring ketosynthase. , 2013, Angewandte Chemie.

[118]  C. Woese Default taxonomy: Ernst Mayr's view of the microbial world. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[119]  O. Werz,et al.  Myxochelins target human 5-lipoxygenase. , 2015, Journal of Natural Products.

[120]  A. Aumelas,et al.  Identification of a new antimicrobial lysine-rich cyclolipopeptide family from Xenorhabdus nematophila , 2009, The Journal of Antibiotics.

[121]  W. Blankenfeldt,et al.  Total Biosynthesis of the Pyrrolo[4,2]benzodiazepine Scaffold Tomaymycin on an In Vitro Reconstituted NRPS System. , 2017, Cell chemical biology.

[122]  Anni Kleino,et al.  The Drosophila IMD pathway in the activation of the humoral immune response. , 2014, Developmental and comparative immunology.

[123]  H. Jenke-Kodama,et al.  A Type II Polyketide Synthase is Responsible for Anthraquinone Biosynthesis in Photorhabdus luminescens , 2007, ChemBioChem.

[124]  R. Müller,et al.  Cytotoxic Fatty Acid Amides from Xenorhabdus , 2011, Chembiochem : a European journal of chemical biology.

[125]  R. Müller,et al.  Luminmycins A-C, cryptic natural products from Photorhabdus luminescens identified by heterologous expression in Escherichia coli. , 2012, Journal of natural products.

[126]  T. Stehle,et al.  A ketosynthase homolog uses malonyl units to form esters in cervimycin biosynthesis. , 2012, Nature chemical biology.

[127]  M. Roeffaers,et al.  Small molecule perimeter defense in entomopathogenic bacteria , 2012, Proceedings of the National Academy of Sciences.

[128]  J. Clardy,et al.  A chimeric siderophore halts swarming Vibrio. , 2014, Angewandte Chemie.

[129]  S. Heinemann,et al.  Structure Elucidation and Activity of Kolossin A, the D-/L-Pentadecapeptide Product of a Giant Nonribosomal Peptide Synthetase. , 2015, Angewandte Chemie.

[130]  J. Webster,et al.  Antibiotic production in relation to bacterial growth and nematode development in Photorhabdus--Heterorhabditis infected Galleria mellonella larvae. , 2000, FEMS microbiology letters.

[131]  H. Bode,et al.  Biosynthesis and function of simple amides in Xenorhabdus doucetiae , 2017, Environmental microbiology.

[132]  Gregory L. Challis,et al.  Synergy and contingency as driving forces for the evolution of multiple secondary metabolite production by Streptomyces species , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[133]  Lian-Hui Zhang,et al.  Control of litchi downy blight by zeamines produced by Dickeya zeae , 2015, Scientific Reports.

[134]  A. Vilcinskas,et al.  A Photorhabdus Natural Product Inhibits Insect Juvenile Hormone Epoxide Hydrolase , 2015, Chembiochem : a European journal of chemical biology.

[135]  H. Weber,et al.  Enterotoxicity of a nonribosomal peptide causes antibiotic-associated colitis , 2014, Proceedings of the National Academy of Sciences.

[136]  Ming Sun,et al.  Validation of the Intact Zwittermicin A Biosynthetic Gene Cluster and Discovery of a Complementary Resistance Mechanism in Bacillus thuringiensis , 2011, Antimicrobial Agents and Chemotherapy.

[137]  H. Goodrich-Blair,et al.  Response of Ants to a Deterrent Factor(s) Produced by the Symbiotic Bacteria of Entomopathogenic Nematodes , 2002, Applied and Environmental Microbiology.

[138]  H. Bode,et al.  Rhabdopeptides as Insect‐Specific Virulence Factors from Entomopathogenic Bacteria , 2013, Chembiochem : a European journal of chemical biology.

[139]  H. Schwalbe,et al.  Structure, Biosynthesis, and Occurrence of Bacterial Pyrrolizidine Alkaloids. , 2015, Angewandte Chemie.

[140]  J. Crawford,et al.  Pyrazinone protease inhibitor metabolites from Photorhabdus luminescens , 2016, The Journal of Antibiotics.

[141]  R. Deshaies,et al.  Thiolutin is a zinc chelator that inhibits the Rpn11 and other JAMM metalloproteases. , 2017, Nature chemical biology.

[142]  D. Stanley,et al.  Prostaglandins and Their Receptors in Insect Biology , 2011, Front. Endocrin..

[143]  R. Huber,et al.  A plant pathogen virulence factor inhibits the eukaryotic proteasome by a novel mechanism , 2008, Nature.

[144]  J. Crawford,et al.  Regulating Alternative Lifestyles in Entomopathogenic Bacteria , 2010, Current Biology.

[145]  R. Akhurst,et al.  Phase Variation in Xenorhabdus nematophilus and Photorhabdus luminescens: Differences in Respiratory Activity and Membrane Energization , 1994, Applied and environmental microbiology.

[146]  S. Bulgheresi,et al.  All the microbiology nematodes can teach us , 2016, FEMS microbiology ecology.

[147]  Justine W. Debelius,et al.  Specialized metabolites from the microbiome in health and disease. , 2014, Cell metabolism.

[148]  Gregory S. Stupp,et al.  Chemical detoxification of small molecules by Caenorhabditis elegans. , 2013, ACS chemical biology.

[149]  S. Almo,et al.  Stilbene epoxidation and detoxification in a Photorhabdus luminescens-nematode symbiosis , 2017, The Journal of Biological Chemistry.

[150]  A. Coghlan,et al.  Nematode genome evolution. , 2005, WormBook : the online review of C. elegans biology.

[151]  Ted C. J. Turlings,et al.  Recruitment of entomopathogenic nematodes by insect-damaged maize roots , 2005, Nature.

[152]  R. ffrench-Constant,et al.  Photorhabdus: towards a functional genomic analysis of a symbiont and pathogen. , 2003, FEMS microbiology reviews.

[153]  D. Hall,et al.  Cell Invasion and Matricide during Photorhabdus luminescens Transmission by Heterorhabditis bacteriophora Nematodes , 2008, Applied and Environmental Microbiology.

[154]  Jason M Crawford,et al.  Bacterial symbionts and natural products. , 2011, Chemical communications.

[155]  H. Sahl,et al.  Biosynthetic Origin of the Antibiotic Cyclocarbamate Brabantamide A (SB‐253514) in Plant‐Associated Pseudomonas. , 2014, Chembiochem : a European journal of chemical biology.

[156]  P. Seneci,et al.  Studies on the novel anti-staphyloccal compound nematophin. , 2000, Bioorganic & medicinal chemistry letters.

[157]  S. H. Rhodes,et al.  Biologically active metabolites from Xenorhabdus spp., Part 1. Dithiolopyrrolone derivatives with antibiotic activity. , 1991, Journal of natural products.

[158]  S. Nguyen,et al.  A concise, total synthesis and antibacterial evaluation of 2-hydroxy-1-(1H-indol-3-yl)-4-methylpentan-3-one. , 2010, Bioorganic & medicinal chemistry letters.

[159]  W. Chan,et al.  A tricyclic pyrrolobenzodiazepine produced by Klebsiella oxytoca is associated with cytotoxicity in antibiotic-associated hemorrhagic colitis , 2017, The Journal of Biological Chemistry.

[160]  H. Bode,et al.  Synthesis of szentiamide, a depsipeptide from entomopathogenic Xenorhabdus szentirmaii with activity against Plasmodium falciparum , 2012, Beilstein journal of organic chemistry.

[161]  Steven J. Malcolmson,et al.  Dihydrophenylalanine: a prephenate-derived Photorhabdus luminescens antibiotic and intermediate in dihydrostilbene biosynthesis. , 2011, Chemistry & biology.

[162]  R. Ehlers,et al.  Food signal production of Photorhabdus luminescens inducing the recovery of entomopathogenic nematodes Heterorhabditis spp. in liquid culture , 1998, Applied Microbiology and Biotechnology.

[163]  N. Kelleher,et al.  Hydroxymalonyl-acyl carrier protein (ACP) and aminomalonyl-ACP are two additional type I polyketide synthase extender units , 2006, Proceedings of the National Academy of Sciences.

[164]  J. Milstead Heterorhabditis bacteriophora as a vector for introducing its associated bacterium into the hemocoel of Galleria mellonella larvae , 1979 .

[165]  Marcel Kaiser,et al.  Structure and biosynthesis of xenoamicins from entomopathogenic Xenorhabdus. , 2013, Chemistry.

[166]  Todd A. Ciche,et al.  For the Insect Pathogen Photorhabdus luminescens, Which End of a Nematode Is Out? , 2003, Applied and Environmental Microbiology.

[167]  H. Bode,et al.  Biosynthesis and function of bacterial dialkylresorcinol compounds , 2015, Applied Microbiology and Biotechnology.

[168]  H. Goodrich-Blair,et al.  Immune Signaling and Antimicrobial Peptide Expression in Lepidoptera , 2013, Insects.

[169]  A. Givaudan,et al.  Cabanillasin, a new antifungal metabolite, produced by entomopathogenic Xenorhabdus cabanillasii JM26 , 2013, The Journal of Antibiotics.

[170]  Characterization of Photorhabdusluminescens Growth for the Rearing of the Beneficial Nematode Heterorhabditis bacteriophora , 2012, Indian Journal of Microbiology.

[171]  Alexander R. Martin,et al.  A Single Promoter Inversion Switches Photorhabdus Between Pathogenic and Mutualistic States , 2012, Science.

[172]  M. Fischbach,et al.  A family of pyrazinone natural products from a conserved nonribosomal peptide synthetase in Staphylococcus aureus. , 2010, Chemistry & biology.

[173]  T. Steitz,et al.  Amicoumacin a inhibits translation by stabilizing mRNA interaction with the ribosome. , 2014, Molecular cell.

[174]  R. Müller,et al.  Natural products from myxobacteria: novel metabolites and bioactivities. , 2017, Natural product reports.

[175]  F. Löhr,et al.  Structure and Biosynthesis of Fimsbactins A–F, Siderophores from Acinetobacter baumannii and Acinetobacter baylyi , 2013, Chembiochem : a European journal of chemical biology.

[176]  Rolf Müller,et al.  Full-length RecE enhances linear-linear homologous recombination and facilitates direct cloning for bioprospecting , 2012, Nature Biotechnology.

[177]  Ulrich Brandt,et al.  Xentrivalpeptides A-Q: depsipeptide diversification in Xenorhabdus. , 2012, Journal of natural products.

[178]  A. Batzer,et al.  Antiparasitic chaiyaphumines from entomopathogenic Xenorhabdus sp. PB61.4. , 2014, Journal of natural products.

[179]  C. Walsh,et al.  Identification of the gene cluster for the dithiolopyrrolone antibiotic holomycin in Streptomyces clavuligerus , 2010, Proceedings of the National Academy of Sciences.

[180]  H. Bode,et al.  A natural prodrug activation mechanism in nonribosomal peptide synthesis. , 2011, Nature chemical biology.

[181]  A. Danchin,et al.  The genome sequence of the entomopathogenic bacterium Photorhabdus luminescens , 2003, Nature Biotechnology.

[182]  Christoph Dieterich,et al.  The Pristionchus pacificus genome provides a unique perspective on nematode lifestyle and parasitism , 2008, Nature Genetics.

[183]  K. Ng,et al.  Antimycotic activity of Xenorhabdus bovienii (Enterobacteriaceae) metabolites against Phytophthora infestans on potato plants , 1997 .