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Main Title: Biological effects of paenilamicin, a secondary metabolite antibiotic produced by the honey bee pathogenic bacterium Paenibacillus larvae
Author(s): Garcia-Gonzalez, Eva
Müller, Sebastian
Hertlein, Gillian
Heid, Nina
Süßmuth, Roderich D.
Genersch, Elke
Type: Article
Language Code: en
Abstract: Paenibacillus larvae is the etiological agent of American Foulbrood (AFB) a world-wide distributed devastating disease of the honey bee brood. Previous comparative genome analysis and more recently, the elucidation of the bacterial genome, provided evidence that this bacterium harbors putative functional nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs) and therefore, might produce nonribosomal peptides (NRPs) and polyketides (PKs). Such biosynthesis products have been shown to display a wide-range of biological activities such as antibacterial, antifungal or cytotoxic activity. Herein we present an in silico analysis of the first NRPS/PKS hybrid of P. larvae and we show the involvement of this cluster in the production of a compound named paenilamicin (Pam). For the characterization of its in vitro and in vivo bioactivity, a knock-out mutant strain lacking the production of Pam was constructed and subsequently compared to wild-type species. This led to the identification of Pam by mass spectrometry. Purified Pam-fractions showed not only antibacterial but also antifungal and cytotoxic activities. The latter suggested a direct effect of Pam on honey bee larval death which could, however, not be corroborated in laboratory infection assays. Bee larvae infected with the non-producing Pam strain showed no decrease in larval mortality, but a delay in the onset of larval death. We propose that Pam, although not essential for larval mortality, is a virulence factor of P. larvae influencing the time course of disease. These findings are not only of significance in elucidating and understanding host-pathogen interactions but also within the context of the quest for new compounds with antibiotic activity for drug development.
Issue Date: 2014
Date Available: 14-Jul-2017
DDC Class: 570 Biowissenschaften; Biologie
Subject(s): antibacterial activity
antifungal activity
cytotoxic activity
nonribosomal peptide-polyketide hybrid
paenibacillus larvae
Sponsor/Funder: DFG, GRK 1121, Genetische und immunologische Determinanten von Pathogen-Wirt-Interaktionen
DFG, EXC 314, Unifying Concepts in Catalysis
Journal Title: MicrobiologyOpen
Publisher: Wiley
Publisher Place: Hoboken, NJ [u.a.]
Volume: 3
Issue: 5
Publisher DOI: 10.1002/mbo3.195
Page Start: 642
Page End: 656
EISSN: 2045-8827
Appears in Collections:FG Biologische Chemie » Publications

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