Abstract：
The tigecycline resistance gene tet(X4) has been widely reported in animals and animal products in some Asian countries including China in recent years but only sporadically detected in human. In this study, we investigated the prevalence and genetic features of tet(X4)-positive clinical E. coli strains. A total of 462 fecal samples were collected from patients in four hospitals located in four provinces in China in 2023. Nine tet(X4)-positive E. coli strains were isolated and subjected to characterization of their genetic and phenotypic features by performing antimicrobial susceptibility test, whole-genome sequencing, bioinformatic and phylogenetic analysis. The majority of the test strains were found to exhibit resistance to multiple antimicrobial agents including tigecycline but remained susceptible to colistin and meropenem. A total of seven different sequence types (STs) and an unknown ST type were identified among the nine tet(X4)-positive strains. Notably, the tet(X4) gene in six out of these nine tet(X4)-positive E. coli strains was located in a IncFIA-HI1A-HI1B hybrid plasmid, which was an tet(X4)-bearing epidemic plasmid responsible for dissemination of the tet(X4) gene in China. Furthermore, the tet(X4) gene in four out of nine tet(X4)-positive E. coli isolates could be successfully transferred to E. coli EC600 through conjugation. In conclusion, this study characterized the epidemic tet(X4)-bearing plasmids and tet(X4)-associated genetic environment in clinical E. coli strains, suggested the importance of continuous surveillance of such tet(X4)-bearing plasmids to control the increasingly widespread dissemination of tigecycline-resistant pathogens in clinical settings in China.
摘要：
近年来，在包括中国在内的一些亚洲国家的动物和动物产品中广泛报道了替加环素抗性基因tet（X4），但仅在人类中偶尔发现。在这项研究中,我们调查了tet(X4)阳性临床大肠杆菌菌株的患病率和遗传特征。2023年，共从中国四个省份的四家医院的患者收集了462份粪便样本。分离出9株tet(X4)阳性大肠杆菌菌株，并通过进行抗菌药物敏感性试验对其遗传和表型特征进行表征。全基因组测序，生物信息学和系统发育分析。发现大多数测试菌株对包括替加环素在内的多种抗微生物剂表现出抗性,但仍然对粘菌素和美罗培南敏感。在9个tet（X4）阳性菌株中鉴定出总共7种不同的序列类型（ST）和未知的ST类型。值得注意的是,这9株tet(X4)阳性大肠杆菌中有6株的tet(X4)基因位于IncFIA-HI1A-HI1B杂交质粒中，这是一个携带tet（X4）的流行病质粒，负责在中国传播tet（X4）基因。此外，9个tet(X4)阳性大肠杆菌分离株中的4个中的tet(X4)基因可以通过接合成功地转移到大肠杆菌EC600中。总之,本研究表征了临床大肠杆菌菌株中携带tet（X4）的流行质粒和tet（X4）相关的遗传环境，提示了持续监测这种携带tet(X4)的质粒的重要性,以控制替加环素耐药病原体在中国临床环境中日益广泛的传播.
