Abstract
Brucella species are Gram-negative, facultative intracellular pathogens. They are the main cause of brucellosis, which has led to a global health burden. Adherence of the pathogen to the host cells is the first step in the infection process. The bacteria can adhere to various biotic and abiotic surfaces using their outer membrane proteins. Trimeric autotransporter adhesins (TAAs) are modular homotrimers of various length and domain complexity. They are a diverse, and widespread gene family constituting the type Vc secretion pathway. These adhesins have been established as virulence factors in Brucellaceae. To date, no comprehensive and exhaustive study has been performed on the trimeric autotransporter family in the genus. In the present study, various bioinformatics tools were used to provide a novel evolutionary insight into the sequence and structure of this protein family in Brucellaceae. To this end, a dataset of all trimeric autotransporters from the Brucella genomes was built. Analyses included but were not limited to sequence alignment, phylogenetic tree constructions, codon-based test for selection, clustering of the sequences, and structure (primary to quaternary) predictions. Batch analyzes of the dataset suggested the existence of a few structural domains within the whole population. BatA from the B. abortus 2308 genome was selected as a reference to describe the features of these structural domains. Furthermore, we examined the structural basis for the observed rigidity and resiliency of the protein structure through a molecular dynamics evaluation, which led us to deduce that the random drift results in the non-adaptive evolution of the trimeric autotransporter genes in the Brucella genus. Notably, the modifications have occurred across the genus without interference of gene transmission.
Highlights
Members of the genus Brucella are Gram-negative, facultative intracellular pathogens of the alpha-subclass of Proteobacteria phylum
In all Brucella species, the Trimeric autotransporter adhesins (TAAs) encoding genes are located in chromosome 1; the immediate neighbor of the TAA encoding genes is the invasion-associated locus B [in the case of B. abortus 2308, TAA (BatA, Locus tag: BAB1_0069), which is located 209 nucleotide pairs downstream of the invasion-associated locus B (Ialb, locus tag: BAB1_0070)] (Figure 1)
To determine whether batA is associated with other genes, the operon databases were searched for related locus tags
Summary
Members of the genus Brucella are Gram-negative, facultative intracellular pathogens of the alpha-subclass of Proteobacteria phylum. A damaging zoonotic disease, in a broad range of mammalian hosts. Brucellosis imposes a significant health burden, in developing countries and in the livestock dependent economies (Gopalakrishnan et al, 2016). The typical species within the Brucellae genus share a high level of genomic identity. This observation initially led to the conclusion that Brucella is a monospecific genus (B. melitensis), which contained six biovars based on their host prevalence. Recent molecular analyses suggest that B. abortus, B. melitensis, B. neotomae, and B. ovis are four related clones of one organism; whereas, B. suis forms a separate cluster (Foster et al, 2009; Whatmore, 2009). The most economically significant species are B. abortus, B. melitensis, and B. suis
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