title: Production of the catechol type siderophore bacillibactin by the honey bee pathogen Paenibacillus larvae.
abstract: The Gram-positive bacterium Paenibacillus larvae is the etiological agent of American Foulbrood. This bacterial infection of honey bee brood is a notifiable epizootic posing a serious threat to global honey bee health because not only individual larvae but also entire colonies succumb to the disease. In the recent past considerable progress has been made in elucidating molecular aspects of host pathogen interactions during pathogenesis of P. larvae infections. Especially the sequencing and annotation of the complete genome of P. larvae was a major step forward and revealed the existence of several giant gene clusters coding for non-ribosomal peptide synthetases which might act as putative virulence factors. We here present the detailed analysis of one of these clusters which we demonstrated to be responsible for the biosynthesis of bacillibactin, a P. larvae siderophore. We first established culture conditions allowing the growth of P. larvae under iron-limited conditions and triggering siderophore production by P. larvae. Using a gene disruption strategy we linked siderophore production to the expression of an uninterrupted bacillibactin gene cluster. In silico analysis predicted the structure of a trimeric trithreonyl lactone (DHB-Gly-Thr)3 similar to the structure of bacillibactin produced by several Bacillus species. Mass spectrometric analysis unambiguously confirmed that the siderophore produced by P. larvae is identical to bacillibactin. Exposure bioassays demonstrated that P. larvae bacillibactin is not required for full virulence of P. larvae in laboratory exposure bioassays. This observation is consistent with results obtained for bacillibactin in other pathogenic bacteria.
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: Technische Universität Berlin, Institut für Chemie, Berlin, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Müller
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: Lena
authors.initials: L
authors.lastname: Poppinga
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, Institute of Microbiology and Epizootics, Berlin, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Genersch
mesh_terms: D000818:Animals; D001516:Bees / Q000382:microbiology*; D003198:Computer Simulation; D054884:Host-Pathogen Interactions; D013058:Mass Spectrometry; D009842:Oligopeptides / Q000096:biosynthesis* / Q000737:chemistry; D056507:Paenibacillus / Q000378:metabolism* / Q000472:pathogenicity; D017262:Siderophores / Q000096:biosynthesis* / Q000737:chemistry; D037521:Virulence Factors / Q000096:biosynthesis* / Q000737:chemistry
chemical_list: D009842:Oligopeptides; D017262:Siderophores; D037521:Virulence Factors; C430721:bacillibactin