Paenilarvins: Iturin Family Lipopeptides from the Honey Bee Pathogen Paenibacillus larvae

Abstract

The bacterium Paenibacillus larvae has been extensively studied as it is an appalling honey bee pathogen. In the present work, we screened crude extracts derived from fermentations of P. larvae genotypes ERIC I and II for antimicrobial activity, following the detection of four putative secondary metabolite gene clusters that show high sequence homology to known biosynthetic gene clusters for the biosynthesis of antibiotics. Low molecular weight metabolites produced by P. larvae have recently been shown to have toxic effects on honey bee larvae. Moreover, a novel tripeptide, sevadicin, was recently characterized from laboratory cultures of P. larvae. In this study, paenilarvins, which are iturinic lipopeptides exhibiting strong antifungal activities, were obtained by bioassay-guided fractionation from cultures of P. larvae, genotype ERIC II. Their molecular structures were determined by extensive 2D NMR spectroscopy, high resolution mass spectrometry, and other methods. Paenilarvins are the first antifungal secondary metabolites to be identified from P. larvae. In preliminary experiments, these lipopeptides also affected honey bee larvae and might thus play a role in P. larvae survival and pathogenesis. However, further studies are needed to investigate their function.

Identification and classification of known and putative antimicrobial compounds produced by a wide variety of Bacillales species

“…Paenilarvins are iturinic LPs exhibiting strong antifungal activities [177–180]. Paenilarvin A and B were first isolated from P. larve strain, whose NRPS gene clusters showed similarities with those of the iturin family LPs [180].…”

“…Paenilarvins are iturinic LPs exhibiting strong antifungal activities [177–180]. Paenilarvin A and B were first isolated from P. larve strain, whose NRPS gene clusters showed similarities with those of the iturin family LPs [180]. Zwittermicin A is also a hybrid polyketide-nonribosomal peptide produced by certain B. cereus group strains, inhibiting certain Gram-positive, Gram-negative, and eukaryotic microorganisms [181, 182].…”

Current knowledge and perspectives of Paenibacillus: a review

“…Further attributing to the pathogenicity of P. larvae are the paenilimicins and paenilarvins that it produces. Paenilimicins are antimicrobials that fight ecological niche competitors and are not directly involved in killing the bee larvae, while paenilarvins are antifungal compounds which also negatively affect bee larvae [142, 143]. As such, paenilicmins and paenilarvins promote the survival and colonization of P. larvae within honeybee larvae, while paenilarvins have the added disadvantage of directly impacting the health of the bee.…”

“…ERIC II produces four paenilimicins: A1, A2, B1, and B2. In addition, paenilarvins A and B are produced as a secondary metabolite during the infection of P. larvae [143]. Other nonribosomal peptides and peptide-polyketide hybrids are P. larvae secondary metabolites which are expected to have additional roles in the bacteria’s pathogenicity [149].…”

Characterization of Novel Fusaricidins Produced by Paenibacillus polymyxa-M1 Using MALDI-TOF Mass Spectrometry

“…The most frequent products are lipopeptides [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16], peptide/polyketide hybrids [17,18], as well as lantibiotics [19,20]. Such products qualify Paenibacillus strains for applications in agriculture, medicine, and biotechnology.…”