Whole genome sequencing characterization of the new KPC-245 variant-carrying Klebsiella pneumoniae strain isolated from a transplanted patient and resistant to ceftazidime/avibactam, meropenem/vaborbactam and imipenem/relebactam.
Claudia Vaiana, Roberta Vazzana, Salvatore Castelbuono, Andrea Cona, Alessandra Mularoni, Rita Minucci, Francesco Monaco, Daniele Di Carlo, Pier Giulio Conaldi, Alessia Gallo, Nicola Cuscino
{"title":"Whole genome sequencing characterization of the new KPC-245 variant-carrying Klebsiella pneumoniae strain isolated from a transplanted patient and resistant to ceftazidime/avibactam, meropenem/vaborbactam and imipenem/relebactam.","authors":"Claudia Vaiana, Roberta Vazzana, Salvatore Castelbuono, Andrea Cona, Alessandra Mularoni, Rita Minucci, Francesco Monaco, Daniele Di Carlo, Pier Giulio Conaldi, Alessia Gallo, Nicola Cuscino","doi":"10.1016/j.jgar.2025.03.006","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>Across recent decades the increasing prevalence of multi-drug resistant KPC-carrying K. pneumoniae (KPC-Kp) has become a worldwide public concern. Herein, we characterized a ceftazidime/avibactam (CAZ/AVI), meropenem/vaborbactam (MER-VAB) and imipenem/relebactam (IMI-REL) resistant KPC-Kp strain isolated from a critically ill transplanted patient.</p><p><strong>Methods: </strong>Antimicrobial susceptibility test and whole-genome sequencing (WGS) were conducted to characterize the strain at the phenotypic and the genotypic levels. Genomic DNA was sequenced using the Illumina platform. Bioinformatic analyses were used to investigate the genome sequences both for resistance and virulence features, and for characterization of plasmids.</p><p><strong>Results: </strong>The phenotypic characterization revealed that the KPC-Kp isolate was highly resistant to a wide range of antibiotics, including all the beta-lactam/beta lactamase inhibitor combinations, such as CAZ/AVI, MER-VAB, IMI-REL, and cefiderocol (FDC). WGS analysis showed that the isolate, belonging to the rare lineage ST661, contained several resistance and virulence genes. Among the resistance genes, we identified a new KPC variant, inside the mobile genetic element Tn4401, KPC-245, characterized by an insertion of 9 aminoacids (RAPNKDDYT) at position 263 and an aminoacidic change E274D of the protein sequence, compared to KPC-3. Interestingly, the presence of mutations only in bla<sub>KPC</sub> gene, and not in other beta-lactamases coding genes, strongly points KPC-245 role in beta-lactam/beta-lactamase inhibitor combinations and FDC resistance.</p><p><strong>Conclusions: </strong>In our study, by using WGS analysis on a clinical isolate, we identified a new bla<sub>KPC</sub> variant inside the Tn4401 transposon. Our results confirm the important role of the continuous surveillance of MDR K. pneumoniae in the clinical context.</p>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":" ","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of global antimicrobial resistance","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jgar.2025.03.006","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
引用次数: 0
Abstract
Objectives: Across recent decades the increasing prevalence of multi-drug resistant KPC-carrying K. pneumoniae (KPC-Kp) has become a worldwide public concern. Herein, we characterized a ceftazidime/avibactam (CAZ/AVI), meropenem/vaborbactam (MER-VAB) and imipenem/relebactam (IMI-REL) resistant KPC-Kp strain isolated from a critically ill transplanted patient.
Methods: Antimicrobial susceptibility test and whole-genome sequencing (WGS) were conducted to characterize the strain at the phenotypic and the genotypic levels. Genomic DNA was sequenced using the Illumina platform. Bioinformatic analyses were used to investigate the genome sequences both for resistance and virulence features, and for characterization of plasmids.
Results: The phenotypic characterization revealed that the KPC-Kp isolate was highly resistant to a wide range of antibiotics, including all the beta-lactam/beta lactamase inhibitor combinations, such as CAZ/AVI, MER-VAB, IMI-REL, and cefiderocol (FDC). WGS analysis showed that the isolate, belonging to the rare lineage ST661, contained several resistance and virulence genes. Among the resistance genes, we identified a new KPC variant, inside the mobile genetic element Tn4401, KPC-245, characterized by an insertion of 9 aminoacids (RAPNKDDYT) at position 263 and an aminoacidic change E274D of the protein sequence, compared to KPC-3. Interestingly, the presence of mutations only in blaKPC gene, and not in other beta-lactamases coding genes, strongly points KPC-245 role in beta-lactam/beta-lactamase inhibitor combinations and FDC resistance.
Conclusions: In our study, by using WGS analysis on a clinical isolate, we identified a new blaKPC variant inside the Tn4401 transposon. Our results confirm the important role of the continuous surveillance of MDR K. pneumoniae in the clinical context.
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.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
