Tet(X4)-producing Escherichia coli isolates in Taiwan

Plasmid-mediaed tet(X4), linked to high-level tigecycline resistance, was first identified in China with Escherichia coli (E. coli) as a major reservoir. No confirmed cases had been reported in Taiwan.

We examined 81 tigecycline-resistant E. coli isolates (MIC ≥ 4 mg/L) collected in Taiwan from 2015 to 2022, including 71.6% carbapenem-resistant and 28.4% carbapenem-susceptible strains. Thirty-six underwent whole-genome sequencing to investigate resistance mechanisms.

Two isolates (2.5%) carried tet(X4) on novel plasmids (pEC1360-1 and pEC1638-1). Both plasmids contained the ISVsa3-estT-tet(X4)-ISVsa3 (IETI) element, a mobile unit capable of transposon-mediated transfer without a fixed integration hotspot. The tet(X4)-positive strains showed distinct evolutionary divergence from the first reported Chinese strain (LHM10-1). Tet(X4) was located on different Inc-type plasmids, including a 66.8 kb IncR and a 159.3 kb IncR/IncFIB(K)/IncFIA(HI1) plasmid, across various sequence types. No tet(X4) was detected in carbapenem-resistant isolates. Other resistance genes, such as cmlA1 and floR, were more prevalent in carbapenem-susceptible isolates (66.7% vs. 25.9%, P = 0.077).

This study reports the first tet(X4)-positive E. coli isolates in Taiwan, both from carbapenem-susceptible strains. The presence of novel mobile plasmids underscores the potential for horizontal gene transfer. Continuous surveillance of tet(X) and other last-line antibiotic resistance mechanisms is essential to mitigate the risk of further spread.