MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Key Laboratory of Pathogen Bioscience and Anti-infective Medicine, School of Basic Medical Science, Suzhou Medical College of Soochow University, Suzhou, China; Department of Medical Microbiology, Experimental Center, Suzhou Medical College of Soochow University, Suzhou, China.
Department of Medical Microbiology, School of Basic Medical Science, Suzhou Medical College of Soochow University, Suzhou, China.
J Glob Antimicrob Resist. 2024 Sep;38:158-162. doi: 10.1016/j.jgar.2024.06.003. Epub 2024 Jun 13.
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.
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.
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.
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.
本研究旨在探讨Ⅰ型 tet(A)变体（tetA-v1）对肺炎克雷伯菌适应性的影响。
以临床分离的肺炎克雷伯菌为亲本菌株，构建仅携带质粒载体（pBBR1MCS-5）或 tetA-v1 重组质粒（ptetA-v1）的菌株。药敏试验估计 tetA-v1 对耐药性的贡献。通过在无替加环素的情况下连续传代 10 代评估质粒稳定性。通过生长曲线分析、体外竞争试验和中性粒细胞减少症小鼠大腿感染模型来检测生物适应性。
获得 tetA-v1 后，替加环素 MIC 增加了 2-4 倍。在没有替加环素治疗的情况下，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 质粒减少了约 20%。tetA-v1 基因的获得可以抑制肺炎克雷伯菌株在体外和体内的生长能力。tetA-v1 基因在肺炎克雷伯菌中造成了适应性代价，特别是在 CRKP 菌株 Kp51 中，W 值约为 0.56。
在没有替加环素的情况下，tetA-v1 的存在与肺炎克雷伯菌的显著适应性代价有关，无论是在体外还是体内。
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