Identification of blaKPC-90 in Klebsiella pneumoniae associated with ceftazidime-avibactam resistance and the translocation & truncation of resistant genes mediated by IS26
Weiwei Yang , Heping Xu , Yuanxun Zhao , Wannan Chen , Xiaobo Ma , Fupin Hu
{"title":"Identification of blaKPC-90 in Klebsiella pneumoniae associated with ceftazidime-avibactam resistance and the translocation & truncation of resistant genes mediated by IS26","authors":"Weiwei Yang , Heping Xu , Yuanxun Zhao , Wannan Chen , Xiaobo Ma , Fupin Hu","doi":"10.1016/j.ijantimicag.2024.107388","DOIUrl":null,"url":null,"abstract":"<div><h3>Objectives</h3><div>In this study, we discovered <em>bla</em><sub>KPC-90</sub> in ceftazidime-avibactam resistant clinical isolates of <em>K. pneumoniae</em> from a patient with multiple comorbidities and investigated the resistance & transfer mechanism of <em>bla</em><sub>KPC-90</sub>.</div></div><div><h3>Methods</h3><div><em>K. pneumoniae</em> strains carrying <em>bla</em><sub>KPC-2</sub> and <em>bla</em><sub>KPC-90</sub> were isolated from the patient. Antimicrobial susceptibility tests and whole genome sequencing were performed to investigate the phenotype & genotype of strains. Conjugation assays, cloning experiment, kinetic parameters measuring, outer membrane protein SDS-PAGE and qRT-PCR were performed to explore the spread and antimicrobial resistance mechanisms.</div></div><div><h3>Results</h3><div>KPC-90 isolates had an insertion of two amino acids (Thr180_Ser181 ins Tyr Thr) compared to the wildtype KPC-2. Antimicrobial susceptibility testing of isolates with KPC-90 vs. KPC-2 showed ceftazidime-avibactam MICs of >128 vs. 1–2 mg/L, meropenem-vaborbactam MICs of 4 vs. 1 mg/L, meropenem MICs of 4–8 vs. >128 mg/L and imipenem MICs of 0.5–1 vs. 64 mg/L. Analysis of kinetic parameters of KPC-90 compared to KPC-2 showed decreased hydrolysis of carbapenems and increased IC50 of avibactam. Genetic characterization of the plasmid revealed that IS26 could mediate the intramolecular inversion, translocation and truncation of the resistance determinant region.</div></div><div><h3>Conclusion</h3><div>We have described the case of a patient infected with <em>bla</em><sub>KPC-90</sub>-carrying <em>K. pneumoniae</em> strains and investigated the mechanism of resistance to carbapenems and ceftazidime-avibactam associated with <em>bla</em><sub>KPC-2</sub> and its variants. We have also focused on the functional diversity of IS26 in relation to antimicrobial resistance. In the future, it is crucial to pay more attention to the evolution and horizontal transmission of <em>bla</em><sub>KPC</sub>.</div></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":"65 1","pages":"Article 107388"},"PeriodicalIF":4.9000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Antimicrobial Agents","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0924857924003042","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
引用次数: 0
Abstract
Objectives
In this study, we discovered blaKPC-90 in ceftazidime-avibactam resistant clinical isolates of K. pneumoniae from a patient with multiple comorbidities and investigated the resistance & transfer mechanism of blaKPC-90.
Methods
K. pneumoniae strains carrying blaKPC-2 and blaKPC-90 were isolated from the patient. Antimicrobial susceptibility tests and whole genome sequencing were performed to investigate the phenotype & genotype of strains. Conjugation assays, cloning experiment, kinetic parameters measuring, outer membrane protein SDS-PAGE and qRT-PCR were performed to explore the spread and antimicrobial resistance mechanisms.
Results
KPC-90 isolates had an insertion of two amino acids (Thr180_Ser181 ins Tyr Thr) compared to the wildtype KPC-2. Antimicrobial susceptibility testing of isolates with KPC-90 vs. KPC-2 showed ceftazidime-avibactam MICs of >128 vs. 1–2 mg/L, meropenem-vaborbactam MICs of 4 vs. 1 mg/L, meropenem MICs of 4–8 vs. >128 mg/L and imipenem MICs of 0.5–1 vs. 64 mg/L. Analysis of kinetic parameters of KPC-90 compared to KPC-2 showed decreased hydrolysis of carbapenems and increased IC50 of avibactam. Genetic characterization of the plasmid revealed that IS26 could mediate the intramolecular inversion, translocation and truncation of the resistance determinant region.
Conclusion
We have described the case of a patient infected with blaKPC-90-carrying K. pneumoniae strains and investigated the mechanism of resistance to carbapenems and ceftazidime-avibactam associated with blaKPC-2 and its variants. We have also focused on the functional diversity of IS26 in relation to antimicrobial resistance. In the future, it is crucial to pay more attention to the evolution and horizontal transmission of blaKPC.
期刊介绍：
The International Journal of Antimicrobial Agents is a peer-reviewed publication offering comprehensive and current reference information on the physical, pharmacological, in vitro, and clinical properties of individual antimicrobial agents, covering antiviral, antiparasitic, antibacterial, and antifungal agents. The journal not only communicates new trends and developments through authoritative review articles but also addresses the critical issue of antimicrobial resistance, both in hospital and community settings. Published content includes solicited reviews by leading experts and high-quality original research papers in the specified fields.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
