Horizontal gene transfer and the genomics of enterococcal antibiotic resistance

Abstract

Enterococci are Gram-positive bacteria that normally colonize gastrointestinal tracts of humans and animals. They are of growing concern because of their ability to cause antibiotic resistant hospital infections. Antibiotic resistance has been acquired, and has disseminated throughout enterococci, via horizontal transfer of mobile genetic elements. This transmission has been mediated mainly by conjugative plasmids of the pheromone-responsive and broad host range incompatibility group 18 type. Genome sequencing is revealing the extent of diversity of these and other mobile elements in enterococci, as well as the extent of recombination and rearrangement resulting in new phenotypes. Pheromone-responsive plasmids were recently shown to promote genome plasticity in antibiotic resistant Enterococcus faecalis, and their involvement has been implicated in E. faecium as well. Further, incompatibility group 18 plasmids have recently played an important role in mediating transfer of vancomycin resistance from enterococci to methicillin-resistant strains of S. aureus.

Figure 1

Model for mobilization of antibiotic resistance from E. faecalis (donors) to S. gordonii Challis (recipients) in response to gordonii-cAM373 pheromone [21,62]. (a) S. gordonii Challis cells produce a signal, gordonii-cAM373, that is detected by E. faecalis cells carrying pAM373 via the plasmid-encoded membrane protein, TraC. (b) Conjugative functions are induced on pAM373 by the presence of gordonii-cAM373, leading to mating pore formation and mobilization of a non-conjugative erythromycin resistance plasmid. The result of this interaction is erythromycin-resistant S. gordonii Challis. In the absence of pAM373, no transfer of erythromycin resistance from E. faecalis to S. gordonii Challis occurs (not shown; [21]). Note that a simplified model for pheromone excretion and uptake is shown.

Figure 2

Possible scenarios which allowed for dissemination of vancomycin resistance to MRSA from VRE. Co-colonization of patients with VRE and MRSA allowed for the transfer of pAM830 which carried the transposon (Tn1546) encoding genes associated with high level glycopeptide resistance. Several outcomes appeared to have occurred based upon the analysis of the resultant VRSA strains. It would appear that: (a) only Tn1546 may have been transferred during the conjugation process instigated by pAM830 and recombined on the chromosome of the S. aureus recipient or the complete plasmid was transferred to the S. aureus recipient and was stably maintained; (b) the plasmid carrying Tn1546 was not completely transferred to the recipient cell or incompatibility issues were encountered between pAM830 and existing plasmids in the MRSA strain and the transposon was found in the recipient strain on a native plasmid.