Abstract
Long-term persistence of VanA glycopeptide-resistant enterococci (GRE) has been observed in the absence of antibiotic selection. In the present study, we examined fitness parameters of a glycopeptide-susceptible
Enterococcus faecium
parent strain and its plasmid-mediated, VanA-resistant derivative before and after 1,000 generations in serial transfer broth cultures with or without antibiotic selection. With
the exception of the
vanA
-containing plasmid, the strains were otherwise isogenic. The stability of the plasmid-encoded
vanA
resistance determinant was also investigated
in vitro
and
in gnotobiotic mice. Competition experiments revealed that GRE with newly acquired VanA resistance had a 4% reduction in fitness relative to their susceptible parental counterpart. The relative difference
in competitive fitness between resistant and susceptible strains was not significantly changed after 1,000 generations. Environmental adaptation was observed in all strains and exceeded the biological cost
of resistance. Thus, the evolved VanA-resistant
E. faecium
populations outnumbered their unevolved ancestral susceptible
E. faecium
strain in mixed cultures, but remained less competitive
than the evolved parent. The glycopeptide resistance determinant was similarly stably maintained during long-term colonization in gnotobiotic mice without antibiotic selection.
In vivo vanA
plasmid
transfer was observed. The results suggest that environmental adaptation,
in vivo
gene transfer, and plasmid maintenance system(s) favor long-term VanA GRE persistence without antibiotic selection
and compensate for the biological costs of possessing the resistance genes.