The Buzz about ADP-Ribosylation Toxins from Paenibacillus larvae, the Causative Agent of American Foulbrood in Honey Bees.

Julia Ebeling,Elke Genersch,Anne Fünfhaus

doi:10.3390/toxins13020151

Julia Ebeling, Elke Genersch + Show 1 more

Open Access

https://doi.org/10.3390/toxins13020151

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Journal: Toxins	Publication Date: Feb 16, 2021
Citations: 8	License type: CC BY 4.0

Affiliation: Institute for Bee Research, Freie Universität Berlin

Abstract

The Gram-positive, spore-forming bacterium Paenibacillus larvae is the etiological agent of American Foulbrood, a highly contagious and often fatal honey bee brood disease. The species P. larvae comprises five so-called ERIC-genotypes which differ in virulence and pathogenesis strategies. In the past two decades, the identification and characterization of several P. larvae virulence factors have led to considerable progress in understanding the molecular basis of pathogen-host-interactions during P. larvae infections. Among these virulence factors are three ADP-ribosylating AB-toxins, Plx1, Plx2, and C3larvin. Plx1 is a phage-born toxin highly homologous to the pierisin-like AB-toxins expressed by the whites-and-yellows family Pieridae (Lepidoptera, Insecta) and to scabin expressed by the plant pathogen Streptomyces scabiei. These toxins ADP-ribosylate DNA and thus induce apoptosis. While the presumed cellular target of Plx1 still awaits final experimental proof, the classification of the A subunits of the binary AB-toxins Plx2 and C3larvin as typical C3-like toxins, which ADP-ribosylate Rho-proteins, has been confirmed experimentally. Normally, C3-exoenzymes do not occur together with a B subunit partner, but as single domain toxins. Interestingly, the B subunits of the two P. larvae C3-like toxins are homologous to the B-subunits of C2-like toxins with striking structural similarity to the PA-63 protomer of Bacillus anthracis.

Highlights

Pathogenic bacteria cause disease by infecting their eukaryotic hosts and exploiting them for proliferation and transmission
Causing disease is rather not the “objective” of pathogenic bacteria, but can in most cases be viewed as collateral damage as the bacteria attempt to achieve their primary goals, proliferation, and transmission
Plx1 is highly homologous to two toxins recently considered the enigmatic offspring from the family of ADP-ribosyltransferases [25]: MTX1 expressed by Lysinibacillus sphaericus [23] and the pierisins, a group of ART toxins expressed by the whites-and-yellows family Pieridae (Lepidoptera, Insecta) [26]

Summary

Introduction

Pathogenic bacteria cause disease by infecting their eukaryotic hosts and exploiting them for proliferation and transmission. In contrast to the original assumption, the best homology of the N-terminal A-domain of Plx was not with MTX1 of L. sphaericus [11] but with the A-domains of the pierisins, a group of ART toxins expressed by the whites-and-yellows family Pieridae (Lepidoptera, Insecta) [29]. In addition to the genomic organization of the pierisin-1 gene in the genome of Pieris rapae [52], the existence of the pierisin-homolog Plx expressed by the entomopathogenic bacterium P. larvae [16] was another argument in favor of the hypothesis that a bacterial DNA ADP-ribosylating toxin could be the ancestor of the pierisins [53]. Further studies are necessary to elucidate the stability and regulation of the phage-born plx1-gene, which enables P. larvae to use Plx as a weapon against bee larvae

C3-Like Toxins with B-Subunits

Binary C3-Like Toxin Plx2

Binary C3-Like Toxin C3larvinAB

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