Novelerm(T)-Carrying Multiresistance Plasmids from Porcine and Human Isolates of Methicillin-Resistant Staphylococcus aureus ST398 That Also Harbor Cadmium and Copper Resistance Determinants

Abstract

ABSTRACTThis study describes three novelerm(T)-carrying multiresistance plasmids that also harbor cadmium and copper resistance determinants. The plasmids, designated pUR1902, pUR2940, and pUR2941, were obtained from porcine and human methicillin-resistantStaphylococcus aureus(MRSA) of the clonal lineage ST398. In addition to the macrolide-lincosamide-streptogramin B (MLSB) resistance geneerm(T), all three plasmids also carry the tetracycline resistance genetet(L). Furthermore, plasmid pUR2940 harbors the trimethoprim resistance genedfrKand the MLSBresistance geneerm(C), while plasmids pUR1902 and pUR2941 possess the kanamycin/neomycin resistance geneaadD. Sequence analysis of approximately 18.1 kb of theerm(T)-flanking region from pUR1902, 20.0 kb from pUR2940, and 20.8 kb from pUR2941 revealed the presence of several copies of the recently described insertion sequence ISSau10, which is probably involved in the evolution of the respective plasmids. All plasmids carried a functional cadmium resistance operon with the genescadDandcadX, in addition to the multicopper oxidase genemcoand the ATPase copper transport genecopA, which are involved in copper resistance. The comparative analysis ofS. aureusRN4220 and the threeS. aureusRN4220 transformants carrying plasmid pUR1902, pUR2940, or pUR2941 revealed an 8-fold increase in CdSO4and a 2-fold increase in CuSO4MICs. The emergence of multidrug resistance plasmids that also carry heavy metal resistance genes is alarming and requires further surveillance. The colocalization of antimicrobial resistance genes and genes that confer resistance to heavy metals may facilitate their persistence, coselection, and dissemination.