Comparative ICE Genomics: Insights into the Evolution of the SXT/R391 Family of ICEs

Abstract

Integrating and conjugative elements (ICEs) are one of the three principal types of self-transmissible mobile genetic elements in bacteria. ICEs, like plasmids, transfer via conjugation; but unlike plasmids and similar to many phages, these elements integrate into and replicate along with the host chromosome. Members of the SXT/R391 family of ICEs have been isolated from several species of gram-negative bacteria, including Vibrio cholerae, the cause of cholera, where they have been important vectors for disseminating genes conferring resistance to antibiotics. Here we developed a plasmid-based system to capture and isolate SXT/R391 ICEs for sequencing. Comparative analyses of the genomes of 13 SXT/R391 ICEs derived from diverse hosts and locations revealed that they contain 52 perfectly syntenic and nearly identical core genes that serve as a scaffold capable of mobilizing an array of variable DNA. Furthermore, selection pressure to maintain ICE mobility appears to have restricted insertions of variable DNA into intergenic sites that do not interrupt core functions. The variable genes confer diverse element-specific phenotypes, such as resistance to antibiotics. Functional analysis of a set of deletion mutants revealed that less than half of the conserved core genes are required for ICE mobility; the functions of most of the dispensable core genes are unknown. Several lines of evidence suggest that there has been extensive recombination between SXT/R391 ICEs, resulting in re-assortment of their respective variable gene content. Furthermore, our analyses suggest that there may be a network of phylogenetic relationships among sequences found in all types of mobile genetic elements.

Salmonella Pathogenicity and Host Adaptation in Chicken-Associated Serovars

“…ICEs appear to be major players in the horizontal transfer of genetic material between bacterial species, as they carry genes required for their own excision and transfer to recipient bacteria (113). This is exemplified in Salmonella by SPI-7, an ICE that is present in Salmonella but also among a variety of other Enterobacteriaceae (114).…”

Biology of Three ICE Families: SXT/R391, ICE Bs1 , and ICE St1 /ICE St3

“…Together with other "R factors," R391 was initially identified in the early 1970s as a plasmid conferring resistance to kanamycin and was defined as the prototypical representative of the "IncJ" incompatibility group of plasmids, which included other "R factors" such as R997 from an Indian Proteus mirabilis isolate as well as the socalled plasmids pMERPH from Shewanella putrefaciens and pJY1 from V. cholerae O1 (for a review, see reference 28). More than two decades after the discovery of R391, an accumulation of evidence based on the comparison of integration sites and conservation of a large set of nearly identical genes confirmed that SXT as well as all of the "IncJ elements" belong to the same family of ICEs, referred to as the SXT/R391 family (29,30,31,32).…”

“…SXT/R391 ICEs are major contributors to the spread of multidrug resistance in V. cholerae (27,31,32). In fact, most SXT/R391 ICEs found in clinical isolates confer resistance to sulfamethoxazole and trimethoprim, two commonly used antibiotics.…”

Folded DNA in Action: Hairpin Formation and Biological Functions in Prokaryotes

“…Another effect of SOS induction is the derepression of genes involved in the single-stranded transfer of integrating conjugative elements (ICEs), such as SXT from V. cholerae, which is a ϳ100-kb ICE that transfers and integrates the recipient bacterium's genome, conferring resistance to several antibiotics (11). Moreover, different ICEs are able to combine and create their own diversity in a RecA-dependent manner (i.e., using homologous recombination, which is also induced by SOS) (50,156). As for R plasmids, SXT transfer was observed to induce SOS in V. cholerae.…”