Brucella Genomics: Macro and Micro Evolution

Abstract

Brucella organisms are responsible for one of the most widespread bacterial zoonoses, named brucellosis. The disease affects several species of animals, including humans. One of the most intriguing aspects of the brucellae is that the various species show a ~97% similarity at the genome level. Still, the distinct Brucella species display different host preferences, zoonotic risk, and virulence. After 133 years of research, there are many aspects of the Brucella biology that remain poorly understood, such as host adaptation and virulence mechanisms. A strategy to understand these characteristics focuses on the relationship between the genomic diversity and host preference of the various Brucella species. Pseudogenization, genome reduction, single nucleotide polymorphism variation, number of tandem repeats, and mobile genetic elements are unveiled markers for host adaptation and virulence. Understanding the mechanisms of genome variability in the Brucella genus is relevant to comprehend the emergence of pathogens.

Keywords: Brucella; IS711; SNPs; brucellosis; genome reduction; pseudogene.

Figure 1

The phylogeny of some representative Alphaproteobacteria inferred by maximum likelihood reconstruction based on the 16S rRNA gene. The sequences used as outgroup [14] were trimmed out from the tree to enhance the resolution. The analysis involved 17 nucleotide sequences; there were a total of 1191 positions in the final dataset. Table S1 indicates the details of the strains and sequences used for the analysis. Ochrobactrum intermedium may behave as opportunistic bacteria in immunocompromised human hosts [15,16].

Figure 2

Phylogenetic relationship of “classical” and “non-classical” Brucella species and Ochrobactrum sp. based on 669529 SNPs. Segments of the tree were magnified to increase resolution. The SNPs scale is next to each magnified region. The dotted arrow represents the branch linking the magnified regions to the whole tree. A blue square highlights all Brucella species; the “classical” species are within the up left square. Modified from [77]. In Table S1 are the details of the strains and sequences used for the analysis.

Figure 3

Zoonotic potential of the various Brucella species. The colors and arrow sizes represent the zoonotic risk displayed by each species isolated from its preferred host. Table S2 presents a detailed analysis. Created with Biorender.com.

Figure 4

Pseudogenization mechanisms. Schematic representation of pseudogenes induction found in Brucella after manual curation of genome data (Table S3). (A–C) show pseudogenization induced by polymorphisms that change the length of the CDs by the acquisition of a premature stop codon (A), loss of the start codon (B), or alteration of gene expression by promoter loss or regulatory binding sites (C). Polymorphisms also can induce a functional domain change (D) that results in a different product or frameshift (E). Deletions and insertions, shown in (E,F), can also induce frameshifts.