title: Biological Role of Paenilarvins, Iturin-Like Lipopeptide Secondary Metabolites Produced by the Honey Bee Pathogen Paenibacillus larvae.
abstract: The Gram-positive bacterium Paenibacillus larvae (P. larvae) is the causative agent of a deadly honey bee brood disease called American Foulbrood (AFB). AFB is a notifiable epizootic in most countries and, hence, P. larvae is of considerable relevance for veterinarians and apiculturists alike. Over the last decade, much progress has been made in the understanding of the (patho)biology of P. larvae. Recently, several non-ribosomally produced peptides (NRP) and peptide/polyketide (NRP/PK) hybrids produced by P. larvae were identified. Among these NRPs were iturin-like lipopeptides, the paenilarvins A-C. Iturins are known to exhibit strong anti-fungal activity; for some iturins, cytotoxic activity towards mammalian erythrocytes and human cancer cell lines are described. We here present our results on the analysis of the natural function of the paenilarvins during pathogenesis of P. larvae infections. We demonstrated production of paenilarvins in infected larvae. However, we could neither demonstrate cytotoxicity of paenilarvins towards cultured insect cells nor towards larvae in feeding assays. Accordingly, exposure bioassays performed with larvae infected by wild-type P. larvae and a knockout mutant of P. larvae lacking production of paenilarvins did not substantiate a role for the paenilarvins as virulence factor. Further experiments are necessary to analyze the relevance of the paenilarvins' anti-fungal activity for P. larvae infections in the presence of fungal competitors in the larval midgut or cadaver.
authors.affiliation: Institute for Bee Research, Department of Molecular Microbiology and Bee Diseases, Hohen Neuendorf, Germany.
authors.forename: Gillian
authors.initials: G
authors.lastname: Hertlein
authors.affiliation: Institute for Bee Research, Department of Molecular Microbiology and Bee Diseases, Hohen Neuendorf, Germany.
authors.forename: Marlene
authors.initials: M
authors.lastname: Seiffert
authors.affiliation: Technische Universität Berlin, Institut für Chemie, Berlin, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Gensel
authors.affiliation: Institute for Bee Research, Department of Molecular Microbiology and Bee Diseases, Hohen Neuendorf, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Garcia-Gonzalez
authors.affiliation: Institute for Bee Research, Department of Molecular Microbiology and Bee Diseases, Hohen Neuendorf, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Ebeling
authors.affiliation: Technische Universität Berlin, Institut für Chemie, Berlin, Germany.
authors.forename: Ranko
authors.initials: R
authors.lastname: Skobalj
authors.affiliation: Technische Universität Berlin, Institut für Chemie, Berlin, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Kuthning
authors.affiliation: Technische Universität Berlin, Institut für Chemie, Berlin, Germany.
authors.forename: Roderich D
authors.initials: RD
authors.lastname: Süssmuth
authors.affiliation: Institute for Bee Research, Department of Molecular Microbiology and Bee Diseases, Hohen Neuendorf, Germany.|Freie Universität Berlin, Fachbereich Veterinärmedizin, Institut für Mikrobiologie und Tierseuchen, Berlin, Germany.
authors.forename: Elke
authors.identifier: http://orcid.org/0000-0001-7906-4530
authors.initials: E
authors.lastname: Genersch
mesh_terms: D000818:Animals; D001516:Bees / Q000382:microbiology*; D002460:Cell Line; D007814:Larva / Q000382:microbiology; D055666:Lipopeptides / Q000096:biosynthesis / Q000378:metabolism* / Q000633:toxicity; D051379:Mice; D000070059:Paenibacillus larvae / Q000378:metabolism / Q000502:physiology*
chemical_list: D055666:Lipopeptides