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对中国西南部重庆市一家大型教学医院耐替加环素的分子流行病学特征及耐药机制进行调查。

The investigation of molecular epidemiological characteristics and resistance mechanism of tigecycline resistant from a large teaching hospital in southwest China, Chongqing.

作者信息

Li Yuqiong, Tang Shiyu, Han Qi, Xia Peiwen, Si Tingting, Song Yuanyuan, Xia Yun

机构信息

Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

出版信息

Front Cell Infect Microbiol. 2025 Mar 13;15:1540967. doi: 10.3389/fcimb.2025.1540967. eCollection 2025.

Abstract

BACKGROUND

is one of the main pathogens of nosocomial infection, among which carbapenems can be used for multidrug-resistant . However, in the past decade, the resistance rate of carbapenem-resistant has increased yearly. Tigecycline has good antibacterial activity in treating severe bacterial infections, but the reports of tigecycline resistance are increasing. This study aimed to investigate the mechanism of drug resistance and epidemiological characteristics of tigecycline-resistant (TRKP) in a large teaching hospital in southwest China, Chongqing.

METHODS

We isolated 30 TRKP strains from this hospital between August 2021 and December 2023. By PCR and sequencing, we examined the presence and mutation rates of genes associated with tigecycline resistance, including , and , and performed efflux pump inhibition experiments to verify efflux pump activity. At the same time, real-time RT-PCR was used to detect the expression levels of efflux pump genes ( and ) and To investigate the prevalence trend of TRKP in our hospital, we performed multi-site sequence typing (MLST) analysis.

RESULTS

The mutation rates of (73.3%) and (63.3%) were significant. In efflux pump inhibition experiments, PaβN could reverse the resistance of 29 TRKP strains (96.7%) to tigecycline. Real-time RT-PCR results showed that and genes were up-regulated in 22 strains, while genes were overexpressed in only 4 strains. MLST analysis showed that these strains could be divided into 25 different ST subtypes, indicating that no outbreak of TRKP occurred in our hospital. In addition, two tmexCD-torpj positive strains, ST661 and ST1561, were identified for the first time.

CONCLUSION

The efflux pump and mutations are the primary mechanisms of resistance to at our hospital. The mutation can mediate efflux pump activity of by up-regulating overexpression.

摘要

背景

是医院感染的主要病原菌之一,其中碳青霉烯类可用于治疗多重耐药菌。然而,在过去十年中,耐碳青霉烯类的耐药率逐年上升。替加环素在治疗严重细菌感染方面具有良好的抗菌活性,但替加环素耐药的报道也在增加。本研究旨在调查中国西南部重庆市一家大型教学医院中耐替加环素的(TRKP)的耐药机制和流行病学特征。

方法

2021年8月至2023年12月期间,我们从该医院分离出30株TRKP菌株。通过PCR和测序,我们检测了与替加环素耐药相关基因(包括、和)的存在和突变率,并进行外排泵抑制实验以验证外排泵活性。同时,使用实时RT-PCR检测外排泵基因(和)和的表达水平。为了研究TRKP在我院的流行趋势,我们进行了多位点序列分型(MLST)分析。

结果

(73.3%)和(63.3%)的突变率较高。在外排泵抑制实验中,PaβN可逆转29株TRKP菌株(96.7%)对替加环素的耐药性。实时RT-PCR结果显示,22株菌株中的和基因上调,而只有4株菌株中的基因过表达。MLST分析表明,这些菌株可分为25种不同的ST亚型,表明我院未发生TRKP暴发。此外,首次鉴定出两株tmexCD-torpj阳性菌株,ST661和ST1561。

结论

外排泵和突变是我院对耐药的主要机制。突变可通过上调过表达介导的外排泵活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e45a/11965929/ce849cd8d40a/fcimb-15-1540967-g001.jpg

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