Our analysis of V. cholerae and V. vulnificus genomes suggests up to 20% of their content to have arisen via this route. The continued emergence of novel pathogenic clones carrying diverse combinations of phenotypic and genotypic properties significantly hampers control of the disease. The emergence of V. cholerae O139, one of the two strains responsible for epidemic Asiatic cholera, appears to be a result of LGT from multiple and diverse descendants of the seventh pandemic O1 El Tor strain. Recent studies have indicated that the O1 and O139 associated virulence genes are also dispersed among environmental strains of V. cholerae. LGT and acquisition of virulence genes is then a very likely mechanism for the emergence of pandemic strains of V. cholerae from non-pathogenic environmental strains. The mobilization and integration of mobile gene clusters carrying genes for multiple antibiotic resistance, although not directly implicated in the mechanism of pathogenicity, are also thought to significantly influence the epidemiology of cholera. One important mediator of LGT involves mobile gene cassettes clustered in association with integrons. Gene cassettes are GDC-0449 captured by integrons via their intrinsic site-specific recombination system and constitute the smallest known mobilisable genetic element. Integrons themselves can be found on mobile elements as well as in the chromosome. While most integron cassette arrays contain relatively small numbers of cassettes, extremely large arrays appear particularly prevalent for Vibrio species. Rearrangements and deletions/insertions of large portions of these mobile gene arrays appear to be common events, and arrays can display high levels of diversity even in strains that are PLX-4720 otherwise closely related. Independent studies continue to show that gene cassettes possess a very high proportion of genetic novelty, whether derived from defined strains or from metagenomic surveys. In this work, we focus on one integron gene cassette isolated from a strain of V. cholerae resident within a brackish coastal environment in north-eastern USA. Initial sequencing identified the gene cassette to encode a domain with some homology to the AraC superfamily of transcription activators, generally implicated in the regulation of stress response and virulence. These regulators are well characterized to be modular systems, and include the AraC, MarR and MerR protein families. Generally, these are organized with a DNA-binding domain that acts as a positive regulator of transcription fused to an effector domain which provides a binding site for a specific chemical activator molecule. The modularity of these systems provides capacity for complex regulatory networks, which can also incorporate the membrane transporters for extrusion of multiple toxic agents or drugs.
With two siRNA duplexes targeting each mRNA transcript
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