Fitness cost of tet(A) type I variant-mediated tigecycline resistance in Klebsiella pneumoniae

IF 3.7 3区 医学 Q2 INFECTIOUS DISEASES Journal of global antimicrobial resistance Pub Date : 2024-06-13 DOI:10.1016/j.jgar.2024.06.003
Yuanyuan Li , Tianyu Wang , Yunbing Li , Chen Xu , Tianyi Wang , Lili Huang , Xiangkun Zeng , Guangfen Zhang , Chunli Li , Ning Dong
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Abstract

Objective

The aim of the present study is to explore the impact of the tet(A) type I variant (tetA-v1) on its fitness effect in Klebsiella pneumoniae.

Methods

Clinical K. pneumoniae strains were utilized as parental strains to generate strains carrying only the plasmid vector (pBBR1MCS-5) or the tetA-v1 recombinant plasmid (ptetA-v1). Antimicrobial susceptibility testing was conducted to estimate the contribution of tetA-v1 to drug resistance. Plasmid stability was evaluated by serial passage over 10 consecutive days in the absence of tigecycline. Biological fitness was examined through growth curve analysis, in vitro competition assays and a neutropenic mouse thigh infection model.

Results

A 2–4-fold increase in tigecycline MIC was observed following the acquisition of tetA-v1. Without tigecycline treatment, the stability of ptetA-v1 plasmids has been decreasing since day 1. The ptetA-v1 plasmid in Kp89, Kp91, and Kp93 exhibited a decrease of about 20% compared to the pBBR1MCS-5 plasmid. The acquisition of the tetA-v1 gene could inhibit the growth ability of K. pneumoniae strains both in vitro and in vivo. tetA-v1 gene imposed a fitness cost in K. pneumoniae, particularly in the CRKP strain Kp51, with a W value of approximately 0.56.

Conclusion

The presence of tetA-v1 is associated with a significant fitness cost in K. pneumoniae in the absence of tigecycline, both in vitro and in vivo.

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肺炎克雷伯氏菌对 tet(A) I 型变体介导的替加环素耐药性的健身成本。
研究目的本研究旨在探讨 tet(A) I 型变体(tetA-v1)对肺炎克雷伯氏菌适宜性的影响:方法:以临床肺炎克雷伯菌株为亲本,产生仅携带质粒载体(pBBR1MCS-5)或 tetA-v1 重组质粒(ptetA-v1)的菌株。进行了抗菌药物敏感性测试,以估计 tetA-v1 对耐药性的影响。在没有替加环素的情况下,通过连续 10 天的序列通过来评估质粒的稳定性。通过生长曲线分析、体外竞争试验和嗜中性粒细胞小鼠大腿感染模型检测了生物适应性:在没有替加环素处理的情况下,ptetA-v1 质粒的稳定性从第 1 天开始下降。与 pBBR1MCS-5 质粒相比,Kp89、Kp91 和 Kp93 中的 ptetA-v1 质粒降低了约 20%。tetA-v1 基因的获得会抑制肺炎双球菌菌株在体外和体内的生长能力:结论:无论在体外还是体内,在没有替加环素的情况下,tetA-v1 基因的存在都会使肺炎克雷伯菌付出巨大的健康代价。
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来源期刊
Journal of global antimicrobial resistance
Journal of global antimicrobial resistance INFECTIOUS DISEASES-PHARMACOLOGY & PHARMACY
CiteScore
8.70
自引率
2.20%
发文量
285
审稿时长
34 weeks
期刊介绍: The Journal of Global Antimicrobial Resistance (JGAR) is a quarterly online journal run by an international Editorial Board that focuses on the global spread of antibiotic-resistant microbes. JGAR is a dedicated journal for all professionals working in research, health care, the environment and animal infection control, aiming to track the resistance threat worldwide and provides a single voice devoted to antimicrobial resistance (AMR). Featuring peer-reviewed and up to date research articles, reviews, short notes and hot topics JGAR covers the key topics related to antibacterial, antiviral, antifungal and antiparasitic resistance.
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