Genome-Based Inference of a 50-Kilobase Collinear Synteny Block Containing Genes Predicted to Confer Antimicrobial Resistance and Conjugation Is Widespread Across a Putative Genomic Island in Alpha-Proteobacteria

Antibiotic-, biocide-, and metal-resistance genes co-occur in the genomes of multidrug-resistant bacteria. This relationship is more complex than mere physical co-localization. Instead, it arises from co-selection pressures that favor co-regulation and co-resistance. The genomic basis of this co-occurrence remains unclear. We predicted the co-occurrence of Cu(I)-ATPases with other metal-extrusion systems in Methylobacterium extorquens. In this study, we identified a more complex co-occurrence of Cu(I)-ATPases in the pathogen Brucella anthropi ATCC 49188. It comprises five collinear gene clusters spanning 48.5 kb and may be involved in multimetal homeostasis, redox homeostasis, conjugation, and the transport of miscellaneous molecules. We found highly homologous clusters in 43 strains across 3 alpha-proteobacterial orders, isolated from diverse habitats in different countries. Despite these geographical differences and phylogenetic distances, most orthologous genes remain syntenic. We called this gene arrangement a Collinear Synteny Block (CSB). In 20 species, these CSBs reside within an inferred ~110 kb genomic island, which may have contributed to their dispersion. CSBs co-occur with potential antibiotic-resistance genes scattered across the same replicon. This study will advance our understanding of the organization, evolution, and dispersal of resistance genes in bacteria. This genome-mining study is entirely predictive, and the proposed hypothesis requires experimental validation.