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

Sood, Sakshi; Steinmetz, Heinrich; Beims, Hannes; Mohr, Kathrin I.; Stadler, Marc; Djukic, Marvin; Ohe, Werner von der; Steinert, Michael; Daniel, Rolf; Mueller, R. K.

doi:10.1002/chin.201509271

Cited by 7 publications

(27 citation statements)

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“…; Sood et al . ). Subsequently, the peritrophic membrane (PM) that protects the underlying gut epithelium is attacked by chitin‐degrading enzymes, one of which (PlCBP49) was recognized as a key virulence factor (Garcia‐Gonzalez et al .…”

Section: Introductionmentioning

confidence: 97%

“…These endospores germinate in the larval midgut lumen and massively proliferate before breaching the epithelium (Yue et al 2008). Paenibacillus larvae eliminates bacterial competitors in the larval gut by releasing nonribosomal peptides (Garcia-Gonzalez et al 2014a, 2014bHertlein et al 2014;Muller et al 2014;Sood et al 2014). Subsequently, the peritrophic membrane (PM) that protects the underlying gut epithelium is attacked by chitin-degrading enzymes, one of which (PlCBP49) was recognized as a key virulence factor (Garcia-Gonzalez et al 2014c).…”

Section: Introductionmentioning

confidence: 99%

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Unbiased random mutagenesis contributes to a better understanding of the virulent behaviour ofPaenibacillus larvae

et al. 2017

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Aims: American foulbrood, caused by the Gram-positive bacteria Paenibacillus larvae, is one of the most severe bacterial diseases of the European honey bee. The bacterium has been known for long, but only the last decade the mechanisms used by the pathogen to cause disease in its host are starting to unravel. In this study, the knowledge of this virulent behaviour is expanded and several possible virulence factors are suggested. Methods and Results: Identification of possible virulence factors has been done by random mutagenesis to ensure an unbiased approach. A library of mutants was tested for a significant difference in virulence using in vitro exposure assays. Affected loci were characterized and their potential to contribute in virulence of the pathogen was assessed. Conclusions: The identified mutated loci dacB, dnaK, metN, ywqD, lysC, serC and gbpA are known to encode for virulence factors in other bacteria and are suggested to play a similar role in P. larvae. Significance and Impact of the Study: The study identified new possible virulence factors for P. larvae genotype ERIC I in an unbiased way. This contributes to the knowledge and understanding of the possible mechanisms used by this pathogen to colonize and kill its host.

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Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Unbiased random mutagenesis contributes to a better understanding of the virulent behaviour ofPaenibacillus larvae

et al. 2017

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“…These results led to a better understanding of the virulence differences and showed that the two genotypes follow different molecular strategies during the invasive phase of infection (Djukic et al ., ; Poppinga and Genersch, ). Differential production of several secondary metabolites was demonstrated (Garcia‐Gonzalez et al ., ; Hertlein et al ., ; Müller et al ., ; Sood et al ., ) including paenilamicin, which is produced by P. larvae ERIC II only and was shown to suppress the growth of bacterial competitors in the larval gut (Müller et al ., ; Müller et al ., ). A key virulence factor of both P. larvae ERIC I and ERIC II is Pl CBP49, a chitin‐degrading enzyme responsible for the destruction of the peritrophic matrix during infection (Garcia‐Gonzalez and Genersch, ; Garcia‐Gonzalez et al ., ).…”

Section: Introductionmentioning

confidence: 99%

Characterization of the toxin Plx2A, a RhoA‐targeting ADP‐ribosyltransferase produced by the honey bee pathogen Paenibacillus larvae

Ebeling

Fünfhaus

Knispel

et al. 2017

Environmental Microbiology

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The toxin Plx2A is an important virulence factor of Paenibacillus larvae, the etiological agent of American Foulbrood, the most destructive bacterial disease of honey bees. Biochemical and functional analyses as well as the crystal structure of Plx2A revealed that it belongs to the C3 mono-ADP-ribosylating toxin subgroup. RhoA was identified as the cellular target of Plx2A activity. The kinetic parameters (K , k ) were established for both the transferase and glycohydrolase reactions. When expressed in yeast, Plx2A was cytotoxic for eukaryotic cells and catalytic variants confirmed that the cytotoxicity of Plx2A depends on its enzymatic activity. The crystal structure of Plx2A was solved to 1.65 Å and confirmed that it is a C3-like toxin, although with a new molecular twist, it has a B-domain. A molecular model of the 'active' enzyme conformation in complex with NAD was produced by computational methods based on the recent structure of C3bot1 with RhoA. In murine macrophages, Plx2A induced actin cytoskeleton reorganization while in insect cells, vacuolization and the occurrence of bi-nucleated cells was observed. The latter is indicative of an inhibition of cytokinesis. All these cellular effects are consistent with Plx2A inhibiting the activity of RhoA by covalent modification.

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“…, Sood et al. ), although the architecture of the gene clusters shows some variability (e.g., a stand‐alone FAAL in the puwainaphycin gene cluster). Aside from cyclic lipopeptides mentioned thus far, FAAL is involved in the synthesis of the linear lipopeptide microginin (designated as an adenylation domain for octanoic acid; Kramer ) and other cyanobacterial metabolites that contain a fatty acid moiety, namely jamaicamide, hectochlorin and hapalosin (designated as acyl‐ACP synthases in the respective publications; Edwards et al.…”

mentioning

confidence: 99%

“…Seven amino acids are added by NRPS modules and the nascent peptide is released and cyclized by a thioesterase domain (Te-domain). Iturin, bacillomycin, paenilarvin and puwainaphycin are synthesized analogously (Tsuge et al 2001, Koumoutsi et al 2004, Sood et al 2014, although the architecture of the gene clusters shows some variability (e.g., a stand-alone FAAL in the puwainaphycin gene cluster). Aside from cyclic lipopeptides mentioned thus far, FAAL is involved in the synthesis of the linear lipopeptide microginin (designated as an adenylation domain for octanoic acid; Kramer 2010) and other cyanobacterial metabolites that contain a fatty acid moiety, namely jamaicamide, hectochlorin and hapalosin (designated as acyl-ACP synthases in the respective publications; Edwards et al 2004, Ramaswamy et al 2007, Micallef et al 2015b.…”

mentioning

confidence: 99%

Genome mining reveals high incidence of putative lipopeptide biosynthesis NRPS/PKS clusters containing fatty acyl‐AMP ligase genes in biofilm‐forming cyanobacteria

Galica

Hrouzek

Mareš

2017

Journal of Phycology

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Cyanobacterial lipopeptides have antimicrobial and antifungal bioactivities with potential for use in pharmaceutical research. However, due to their hemolytic activity and cytotoxic effects on human cells, they may pose a health issue if produced in substantial amounts in the environment. In bacteria, lipopeptides can be synthesized via several well-evidenced mechanisms. In one of them, fatty acyl-AMP ligase (FAAL) initiates biosynthesis by activation of a fatty acyl residue. We have performed a bioinformatic survey of the cyanobacterial genomic information available in the public databases for the presence of FAAL-containing non-ribosomal peptide synthetase/polyketide synthetase (NRPS/PKS) biosynthetic clusters, as a genetic basis for lipopeptide biosynthesis. We have identified 79 FAAL genes associated with various NRPS/PKS clusters in 16% of 376 cyanobacterial genomic assemblies available, suggesting that FAAL is frequently incorporated in NRPS/PKS biosynthetases. FAAL was present either as a stand-alone protein or fused either to NRPS or PKS. Such clusters were more frequent in derived phylogenetic lineages with larger genome sizes, which is consistent with the general pattern of NRPS/PKS pathways distribution. The putative lipopeptide clusters were more frequently found in genomes of cyanobacteria that live attached to surfaces and are capable of forming microbial biofilms. While lipopeptides are known in other bacterial groups to play a role in biofilm formation, motility, and colony expansion, their functions in cyanobacterial biofilms need to be tested experimentally. According to our data, benthic and terrestrial cyanobacteria should be the focus of a search for novel candidates for lipopeptide drug synthesis and the monitoring of toxic lipopeptide production.

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

Cited by 7 publications

References 1 publication

Unbiased random mutagenesis contributes to a better understanding of the virulent behaviour ofPaenibacillus larvae

Unbiased random mutagenesis contributes to a better understanding of the virulent behaviour ofPaenibacillus larvae

Characterization of the toxin Plx2A, a RhoA‐targeting ADP‐ribosyltransferase produced by the honey bee pathogen Paenibacillus larvae

Genome mining reveals high incidence of putative lipopeptide biosynthesis NRPS/PKS clusters containing fatty acyl‐AMP ligase genes in biofilm‐forming cyanobacteria

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