Spreading Ability of Tet(X)-Harboring Plasmid and Effect of Tetracyclines as a Selective Pressure

Tigecycline is a last-resort antimicrobial in humans. Tetracyclines are the most widely used antimicrobials in livestock. Mobile tigecycline resistance genes [tet(X)] are disseminated worldwide, and tetracycline use may have promoted the selection of tet(X) genes. Thus, the selective pressure on tet(X) genes and their plasmids in livestock must be elucidated. We performed a retrospective study to clarify the prevalence of tigecycline-resistant Escherichia coli from pigs in Thailand. Screening for tigecycline resistance was performed on 107 E. coli strains from 25 samples, and tet(X)-carrying plasmids were characterized. tet(X) genes were cloned and expressed in E. coli. Bacterial growth rate in the presence of tetracycline as a result of the presence of tet(X) genes was also evaluated. Thirty-two tet(X4)-harboring tigecycline-resistant E. coli strains were detected in 10/25 samples (40%). The tet(X4) genes were carried on various Inc-type plasmids and flanked by ISCR2. The tet(X)-carrying plasmids were transferred to E. coli and Klebsiella pneumoniae. Acquisition of tet(X) genes and their plasmids improved bacterial growth in the presence of tetracycline. In summary, tetracycline use exerts selective pressure on tet(X) genes and their various backbone plasmids; therefore, a reduced amount of tetracycline use is important to limit the spreading of tet(X) genes.