{"title":"bla CTX-M-3基因参与肺炎克雷伯菌特殊耐药表型的出现。","authors":"Peishan Li, Leping Yan, Jingjie Song, Chengfeng Lin, Fangyin Zeng, Shihan Zeng","doi":"10.3389/fcimb.2025.1545157","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to investigate the mechanism underlying a peculiar resistance phenotype in <i>Klebsiella pneumoniae</i>, characterized by reduced susceptibility to cefepime compared to ceftazidime.</p><p><strong>Methods: </strong>Antimicrobial susceptibility testing, plasmid conjugation experiments, whole-genome sequencing, and bioinformatic analyses were employed to characterize the resistance phenotype and identify genetic determinants.</p><p><strong>Results: </strong>A total of 20 <i>K. pneumoniae</i> strains exhibiting peculiar resistance phenotypes were collected and analyzed. Ten distinct sequence types (STs) were identified, including ST25 (4/20), ST967 (3/20), ST65 (2/20), ST133 (2/20), ST48 (2/20), ST353 (1/20), ST628 (1/20), ST753 (1/20), ST792 (1/20), and ST254 (1/20). All strains were resistant to FEP (MIC<sub>50</sub> = 128 µg/mL) but not to CAZ (MIC<sub>50</sub> = 8 µg/mL). This resistance was primarily attributed to the presence of the <i>bla</i> <sub>CTX-M-3</sub> (14/20) and <i>bla</i> <sub>OXA-10</sub> (3/20). Conjugation experiments demonstrated that 5 out of 14 <i>bla</i> <sub>CTX-M-3</sub>-positive <i>K. pneumoniae</i> strains successfully acquired transconjugants, which exhibited the same peculiar resistance phenotype. PCR analysis confirmed that the conjugates contained the IncFII plasmid. To further elucidate the genetic basis of the resistance phenotype, whole-genome long-read sequencing was performed on three <i>bla</i> <sub>CTX-M-3</sub>-positive <i>K. pneumoniae</i> strains. The sequencing results confirmed that <i>bla</i> <sub>CTX-M-3</sub> was located on the IncFII plasmid, and analysis of its genetic environment revealed a frequent association with mobile genetic elements such as IS<i>26</i>, IS<i>Ecp1</i>, and Tn<i>3</i>.</p><p><strong>Discussion: </strong>The primary driver of this phenotype in <i>K. pneumoniae</i> is the presence of the IncFII plasmid carrying <i>bla</i> <sub>CTX-M-3</sub>, which contrasts with the resistance mechanisms often reported in <i>Pseudomonas aeruginosa</i> exhibiting similar phenotypes. This study emphasizes the critical role of plasmid-mediated resistance in the spread of multidrug resistance in <i>K. pneumoniae</i> and provides insights into strategies for combating resistance in these pathogens.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1545157"},"PeriodicalIF":4.6000,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106457/pdf/","citationCount":"0","resultStr":"{\"title\":\"Involvement of the <i>bla</i> <sub>CTX-M-3</sub> gene in emergence of a peculiar resistance phenotype in <i>Klebsiella pneumoniae</i>.\",\"authors\":\"Peishan Li, Leping Yan, Jingjie Song, Chengfeng Lin, Fangyin Zeng, Shihan Zeng\",\"doi\":\"10.3389/fcimb.2025.1545157\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>This study aimed to investigate the mechanism underlying a peculiar resistance phenotype in <i>Klebsiella pneumoniae</i>, characterized by reduced susceptibility to cefepime compared to ceftazidime.</p><p><strong>Methods: </strong>Antimicrobial susceptibility testing, plasmid conjugation experiments, whole-genome sequencing, and bioinformatic analyses were employed to characterize the resistance phenotype and identify genetic determinants.</p><p><strong>Results: </strong>A total of 20 <i>K. pneumoniae</i> strains exhibiting peculiar resistance phenotypes were collected and analyzed. Ten distinct sequence types (STs) were identified, including ST25 (4/20), ST967 (3/20), ST65 (2/20), ST133 (2/20), ST48 (2/20), ST353 (1/20), ST628 (1/20), ST753 (1/20), ST792 (1/20), and ST254 (1/20). All strains were resistant to FEP (MIC<sub>50</sub> = 128 µg/mL) but not to CAZ (MIC<sub>50</sub> = 8 µg/mL). This resistance was primarily attributed to the presence of the <i>bla</i> <sub>CTX-M-3</sub> (14/20) and <i>bla</i> <sub>OXA-10</sub> (3/20). Conjugation experiments demonstrated that 5 out of 14 <i>bla</i> <sub>CTX-M-3</sub>-positive <i>K. pneumoniae</i> strains successfully acquired transconjugants, which exhibited the same peculiar resistance phenotype. PCR analysis confirmed that the conjugates contained the IncFII plasmid. To further elucidate the genetic basis of the resistance phenotype, whole-genome long-read sequencing was performed on three <i>bla</i> <sub>CTX-M-3</sub>-positive <i>K. pneumoniae</i> strains. The sequencing results confirmed that <i>bla</i> <sub>CTX-M-3</sub> was located on the IncFII plasmid, and analysis of its genetic environment revealed a frequent association with mobile genetic elements such as IS<i>26</i>, IS<i>Ecp1</i>, and Tn<i>3</i>.</p><p><strong>Discussion: </strong>The primary driver of this phenotype in <i>K. pneumoniae</i> is the presence of the IncFII plasmid carrying <i>bla</i> <sub>CTX-M-3</sub>, which contrasts with the resistance mechanisms often reported in <i>Pseudomonas aeruginosa</i> exhibiting similar phenotypes. This study emphasizes the critical role of plasmid-mediated resistance in the spread of multidrug resistance in <i>K. pneumoniae</i> and provides insights into strategies for combating resistance in these pathogens.</p>\",\"PeriodicalId\":12458,\"journal\":{\"name\":\"Frontiers in Cellular and Infection Microbiology\",\"volume\":\"15 \",\"pages\":\"1545157\"},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2025-05-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106457/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Cellular and Infection Microbiology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3389/fcimb.2025.1545157\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Cellular and Infection Microbiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fcimb.2025.1545157","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
本研究旨在探讨肺炎克雷伯菌一种特殊耐药表型的机制，其特征是与头孢他啶相比，对头孢吡肟的敏感性降低。方法：采用药敏试验、质粒偶联实验、全基因组测序和生物信息学分析等方法对耐药表型进行表征，并确定遗传决定因素。结果：共收集并分析了20株具有特殊耐药表型的肺炎克雷伯菌。共鉴定出ST25（4/20）、ST967（3/20）、ST65（2/20）、ST133（2/20）、ST48（2/20）、ST353（1/20）、ST628（1/20）、ST753（1/20）、ST792（1/20）、ST254（1/20）等10种不同的序列类型（STs）。所有菌株对FEP （MIC50 = 128µg/mL）均耐药，对CAZ （MIC50 = 8µg/mL）无耐药。这种耐药主要归因于bla CTX-M-3（14/20）和bla OXA-10（3/20）的存在。偶联实验表明，14株bla ctx - m -3阳性肺炎克雷伯菌中有5株成功获得了转偶联物，并表现出相同的特殊抗性表型。PCR分析证实该偶联物含有IncFII质粒。为了进一步阐明耐药表型的遗传基础，对3株bla ctx - m -3阳性肺炎克雷伯菌进行了全基因组长读测序。测序结果证实bla CTX-M-3位于IncFII质粒上，遗传环境分析显示bla CTX-M-3与IS26、ISEcp1、Tn3等移动遗传元件存在密切关联。讨论：肺炎克雷勃菌这种表型的主要驱动因素是携带bla CTX-M-3的IncFII质粒的存在，这与具有类似表型的铜绿假单胞菌中经常报道的耐药机制形成对比。本研究强调了质粒介导的耐药在肺炎克雷伯菌多药耐药传播中的关键作用，并为对抗这些病原体的耐药策略提供了见解。
Involvement of the blaCTX-M-3 gene in emergence of a peculiar resistance phenotype in Klebsiella pneumoniae.
Introduction: This study aimed to investigate the mechanism underlying a peculiar resistance phenotype in Klebsiella pneumoniae, characterized by reduced susceptibility to cefepime compared to ceftazidime.
Methods: Antimicrobial susceptibility testing, plasmid conjugation experiments, whole-genome sequencing, and bioinformatic analyses were employed to characterize the resistance phenotype and identify genetic determinants.
Results: A total of 20 K. pneumoniae strains exhibiting peculiar resistance phenotypes were collected and analyzed. Ten distinct sequence types (STs) were identified, including ST25 (4/20), ST967 (3/20), ST65 (2/20), ST133 (2/20), ST48 (2/20), ST353 (1/20), ST628 (1/20), ST753 (1/20), ST792 (1/20), and ST254 (1/20). All strains were resistant to FEP (MIC50 = 128 µg/mL) but not to CAZ (MIC50 = 8 µg/mL). This resistance was primarily attributed to the presence of the blaCTX-M-3 (14/20) and blaOXA-10 (3/20). Conjugation experiments demonstrated that 5 out of 14 blaCTX-M-3-positive K. pneumoniae strains successfully acquired transconjugants, which exhibited the same peculiar resistance phenotype. PCR analysis confirmed that the conjugates contained the IncFII plasmid. To further elucidate the genetic basis of the resistance phenotype, whole-genome long-read sequencing was performed on three blaCTX-M-3-positive K. pneumoniae strains. The sequencing results confirmed that blaCTX-M-3 was located on the IncFII plasmid, and analysis of its genetic environment revealed a frequent association with mobile genetic elements such as IS26, ISEcp1, and Tn3.
Discussion: The primary driver of this phenotype in K. pneumoniae is the presence of the IncFII plasmid carrying blaCTX-M-3, which contrasts with the resistance mechanisms often reported in Pseudomonas aeruginosa exhibiting similar phenotypes. This study emphasizes the critical role of plasmid-mediated resistance in the spread of multidrug resistance in K. pneumoniae and provides insights into strategies for combating resistance in these pathogens.
期刊介绍：
Frontiers in Cellular and Infection Microbiology is a leading specialty journal, publishing rigorously peer-reviewed research across all pathogenic microorganisms and their interaction with their hosts. Chief Editor Yousef Abu Kwaik, University of Louisville is supported by an outstanding Editorial Board of international experts. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
Frontiers in Cellular and Infection Microbiology includes research on bacteria, fungi, parasites, viruses, endosymbionts, prions and all microbial pathogens as well as the microbiota and its effect on health and disease in various hosts. The research approaches include molecular microbiology, cellular microbiology, gene regulation, proteomics, signal transduction, pathogenic evolution, genomics, structural biology, and virulence factors as well as model hosts. Areas of research to counteract infectious agents by the host include the host innate and adaptive immune responses as well as metabolic restrictions to various pathogenic microorganisms, vaccine design and development against various pathogenic microorganisms, and the mechanisms of antibiotic resistance and its countermeasures.
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