IncHI1 plasmids, a dynamic link between resistance and pathogenicity

Plasmids of incompatibility group (Inc) HI1 are important vectors of antibiotic resistance in both of the major causal agents of enteric fever: Salmonella enterica subspecies enterica serovar Typhi and S. Paratyphi A. In S. Typhi, IncHI1 plasmids appeared in the 1970s and spread globally. In some circumstances they are maintained within the bacterial population even in the absence of selection from antibiotics. The low cost associated with IncH plasmids in Salmonella is due, in part, to the presence of a plasmid gene encoding an H-NS-like global regulator which acts co-operatively with chromosomally encoded H-NS. Very recently, IncHI1 plasmids have crossed from S. Typhi into S. Paratyphi A; the acquisition of drug resistance and possibly other phenotypic traits encoded by IncHI1 plasmids has increased the virulence potential of this neglected pathogen. There is no vaccine for S. Paratyphi A and resistance to the current drugs of choice, the fluoroquinolones, is also spreading rapidly. There is a conserved backbone to all IncH plasmids but variation occurs in regions of the plasmids associated with antibiotic resistance. These IncHI1 plasmids are allowing major human pathogens to sample genes available in their environment, the human gut, and will be maintained by enhancing the competitive advantage of the bacterial host. Therefore competition between closely related resistance plasmids will probably increase the transmission of enteric fever by enhancing the fitness of their bacterial hosts.