Distribution and spread of tigecycline resistance gene (X4) in from different sources.

Tigecycline serves as a last-resort antimicrobial agent against severe infections caused by multidrug-resistant bacteria. Tet(X) and its numerous variants encoding flavin-dependent monooxygenase can confer resistance to tigecycline, with (X4) being the most prevalent variant. This study aims to investigate the prevalence and characterize tigecycline resistance gene (X) in isolates from various origins in Yangzhou, China, to provide insights into (X) dissemination in this region. In 2022, we tested the presence of (X) in 618 isolates collected from diverse sources, including patients, pig-related samples, chicken-related samples, and vegetables in Yangzhou, China. The antimicrobial susceptibility of (X)-positive isolates was conducted using the agar dilution method or the broth microdilution method. Whole genome sequencing was performed on (X)-positive strains using Illumina and Oxford Nanopore platforms. Four isolates from pig or pork samples carried (X4) and exhibited resistance to multiple antimicrobial agents, including tigecycline. They were classified as ST542, ST10, ST761, and ST48, respectively. The (X4) gene was located on IncFIA8-IncHI1/ST17 (n=2), IncFIA18-IncFIB(K)-IncX1 (n=1), and IncX1 (n=1) plasmids, respectively. These (X4)-carrying plasmids exhibited high similarity to other (X4)-bearing plasmids with the same incompatible types found in diverse sources in China. They shared related genetic environments of (X4) associated with IS, as observed in the first identified (X4)-bearing plasmid p47EC. In conclusion, although a low prevalence (0.65%) of (X) in strains was observed in this study, the horizontal transfer of (X4) among isolates mediated by pandemic plasmids and the mobile element IS raises great concerns. Thus, heightened surveillance and immediate action are imperative to curb this clinically significant resistance gene and preserve the efficacy of tigecycline.