AUTHOR=Cloeckaert Axel , Vergnaud Gilles , Zygmunt Michel S. 

TITLE=Omp2b Porin Alteration in the Course of Evolution of Brucella spp.

JOURNAL=Frontiers in Microbiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.00284

DOI=10.3389/fmicb.2020.00284

ISSN=1664-302X

ABSTRACT=<p>The genus <italic>Brucella</italic> comprises major pathogenic species causing disease in livestock and humans, e.g. <italic>B. melitensis</italic>. In the past few years, the genus has been significantly expanded by the discovery of phylogenetically more distant lineages comprising strains from diverse wildlife animal species, including amphibians and fish. The strains represent several potential new species, with <italic>B. inopinata</italic> as solely named representative. Being genetically more distant between each other, relative to the “classical” <italic>Brucella</italic> species, they present distinct atypical phenotypes and surface antigens. Among surface protein antigens, the Omp2a and Omp2b porins display the highest diversity in the classical <italic>Brucella</italic> species. The genes coding for these proteins are closely linked in the <italic>Brucella</italic> genome and oriented in opposite directions. They share between 85 and 100% sequence identity depending on the <italic>Brucella</italic> species, biovar, or genotype. Only the <italic>omp2b</italic> gene copy has been shown to be expressed and genetic variation is extensively generated by gene conversion between the two copies. In this study, we analyzed the <italic>omp2</italic> loci of the non-classical <italic>Brucella</italic> spp. Starting from two distinct ancestral genes, represented by Australian rodent strains and <italic>B. inopinata</italic>, a stepwise nucleotide reduction was observed in the <italic>omp2b</italic> gene copy. It consisted of a first reduction affecting the region encoding the surface L5 loop of the porin, previously shown to be critical in sugar permeability, followed by a nucleotide reduction in the surface L8 loop-encoding region. It resulted in a final <italic>omp2b</italic> gene size shared between two distinct clades of non-classical <italic>Brucella</italic> spp. (African bullfrog isolates) and the group of classical <italic>Brucella</italic> species. Further evolution led to complete homogenization of both <italic>omp2</italic> gene copies in some <italic>Brucella</italic> species such as <italic>B. vulpis</italic> or <italic>B. papionis</italic>. The stepwise <italic>omp2b</italic> deletions seemed to be generated through recombination with the respective <italic>omp2a</italic> gene copy, presenting a conserved size among <italic>Brucella</italic> spp., and may involve short direct DNA repeats. Successive Omp2b porin alteration correlated with increasing porin permeability in the course of evolution of <italic>Brucella</italic> spp. They possibly have adapted their porin to survive environmental conditions encountered and to reach their final status as intracellular pathogen.</p>