Rongmu Luo, Guannan Ma, Qian Yu, Zhengqin Tian, Qihang Man, Xiangrong Shu, Xuetong Liu, Yupeng Shi, Lei Zhang, Jingbo Wang
{"title":"从儿童血液中分离出多重bla基因的多药耐药ST11-KL64高毒肺炎克雷伯菌。","authors":"Rongmu Luo, Guannan Ma, Qian Yu, Zhengqin Tian, Qihang Man, Xiangrong Shu, Xuetong Liu, Yupeng Shi, Lei Zhang, Jingbo Wang","doi":"10.3389/fped.2024.1450201","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) poses an increasing public health risk due to its high treatment difficulty and associated mortality, especially in bone marrow transplant (BMT) patients. The emergence of strains with multiple resistance mechanisms further complicates the management of these infections.</p><p><strong>Methods: </strong>We isolated and characterized a novel ST11-KL64 hv-CRKP strain from a pediatric bone marrow transplantation patient. Antimicrobial susceptibility testing was performed to determine resistance patterns. Comprehensive genomic analysis was conducted to identify plasmid types, virulence factors, and antimicrobial resistance genes, as well as potential resistance mechanisms associated with mutations and plasmid-mediated variants.</p><p><strong>Results: </strong>The isolated hv-CRKP strain exhibited multidrug resistance to carbapenem, tigecycline, and polymyxin. Genomic analysis revealed that the IncHI1B/repB plasmid carried virulence factors (<i>rmpA, ΔrmpA2, iucABCD, iutA</i>), while IncFII/IncR and IncFII plasmids harbored resistance genes [<i>bla</i> <sub><i>C</i> <i>T</i> <i>X</i> <i>-</i> <i>M</i> <i>-</i> <i>6</i> <i>5</i></sub> <i>, bla</i> <sub><i>T</i> <i>E</i> <i>M</i> <i>-</i> <i>1</i> <i>B</i></sub> <i>, rmtB, bla</i> <sub><i>S</i> <i>H</i> <i>V</i> <i>-</i> <i>1</i> <i>2</i></sub> <i>, bla</i> <sub><i>K</i> <i>P</i> <i>C</i> <i>-</i> <i>2</i></sub> <i>, qnrS1, bla</i> <sub><i>L</i> <i>A</i> <i>P</i> <i>-</i> <i>2</i></sub> <i>, sul2, dfrA14, tet(A), tet(R)</i>]. The coexistence of <i>bla</i> <sub><i>C</i> <i>T</i> <i>X</i> <i>-</i> <i>M</i> <i>-</i> <i>6</i> <i>5</i></sub> <i>, bla</i> <sub><i>T</i> <i>E</i> <i>M</i> <i>-</i> <i>1</i> <i>B</i></sub> <i>, bla</i> <sub><i>S</i> <i>H</i> <i>V</i> <i>-</i> <i>1</i> <i>2</i></sub> <i>, bla</i> <sub><i>L</i> <i>A</i> <i>P</i> <i>-</i> <i>2</i></sub> <i>,</i>and <i>bla</i> <sub><i>K</i> <i>P</i> <i>C</i> <i>-</i> <i>2</i></sub> in one hv-CRKP strain is exceptionally rare. Additionally, the Tet(A)-S251A variant in the conjugative plasmid pTET-4 may confer tigecycline resistance. Mutations in MgrB, PhoPQ, and PmrABCDK were identified as potential contributors to increased polymyxin resistance. Interestingly, plasmid-encoded restriction-modification systems and Retron regions were identified, which could potentially confer phage resistance.</p><p><strong>Discussion: </strong>The combination of virulence and antimicrobial resistance factors in the ST11-KL64 hv-CRKP strain represents a significant challenge for treating immunocompromised pediatric patients. Particularly concerning is the resistance to polymyxin and tigecycline, which are often last-resort treatments for multidrug-resistant infections. The findings highlight the urgent need for effective surveillance, infection control measures, and novel therapeutic strategies to manage such hypervirulent and multidrug-resistant pathogens.</p>","PeriodicalId":12637,"journal":{"name":"Frontiers in Pediatrics","volume":"12 ","pages":"1450201"},"PeriodicalIF":2.1000,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743731/pdf/","citationCount":"0","resultStr":"{\"title\":\"Multidrug-resistant ST11-KL64 hypervirulent <i>Klebsiella pneumoniae</i> with multiple <i>bla-</i> genes isolated from children's blood.\",\"authors\":\"Rongmu Luo, Guannan Ma, Qian Yu, Zhengqin Tian, Qihang Man, Xiangrong Shu, Xuetong Liu, Yupeng Shi, Lei Zhang, Jingbo Wang\",\"doi\":\"10.3389/fped.2024.1450201\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) poses an increasing public health risk due to its high treatment difficulty and associated mortality, especially in bone marrow transplant (BMT) patients. The emergence of strains with multiple resistance mechanisms further complicates the management of these infections.</p><p><strong>Methods: </strong>We isolated and characterized a novel ST11-KL64 hv-CRKP strain from a pediatric bone marrow transplantation patient. Antimicrobial susceptibility testing was performed to determine resistance patterns. Comprehensive genomic analysis was conducted to identify plasmid types, virulence factors, and antimicrobial resistance genes, as well as potential resistance mechanisms associated with mutations and plasmid-mediated variants.</p><p><strong>Results: </strong>The isolated hv-CRKP strain exhibited multidrug resistance to carbapenem, tigecycline, and polymyxin. Genomic analysis revealed that the IncHI1B/repB plasmid carried virulence factors (<i>rmpA, ΔrmpA2, iucABCD, iutA</i>), while IncFII/IncR and IncFII plasmids harbored resistance genes [<i>bla</i> <sub><i>C</i> <i>T</i> <i>X</i> <i>-</i> <i>M</i> <i>-</i> <i>6</i> <i>5</i></sub> <i>, bla</i> <sub><i>T</i> <i>E</i> <i>M</i> <i>-</i> <i>1</i> <i>B</i></sub> <i>, rmtB, bla</i> <sub><i>S</i> <i>H</i> <i>V</i> <i>-</i> <i>1</i> <i>2</i></sub> <i>, bla</i> <sub><i>K</i> <i>P</i> <i>C</i> <i>-</i> <i>2</i></sub> <i>, qnrS1, bla</i> <sub><i>L</i> <i>A</i> <i>P</i> <i>-</i> <i>2</i></sub> <i>, sul2, dfrA14, tet(A), tet(R)</i>]. The coexistence of <i>bla</i> <sub><i>C</i> <i>T</i> <i>X</i> <i>-</i> <i>M</i> <i>-</i> <i>6</i> <i>5</i></sub> <i>, bla</i> <sub><i>T</i> <i>E</i> <i>M</i> <i>-</i> <i>1</i> <i>B</i></sub> <i>, bla</i> <sub><i>S</i> <i>H</i> <i>V</i> <i>-</i> <i>1</i> <i>2</i></sub> <i>, bla</i> <sub><i>L</i> <i>A</i> <i>P</i> <i>-</i> <i>2</i></sub> <i>,</i>and <i>bla</i> <sub><i>K</i> <i>P</i> <i>C</i> <i>-</i> <i>2</i></sub> in one hv-CRKP strain is exceptionally rare. Additionally, the Tet(A)-S251A variant in the conjugative plasmid pTET-4 may confer tigecycline resistance. Mutations in MgrB, PhoPQ, and PmrABCDK were identified as potential contributors to increased polymyxin resistance. Interestingly, plasmid-encoded restriction-modification systems and Retron regions were identified, which could potentially confer phage resistance.</p><p><strong>Discussion: </strong>The combination of virulence and antimicrobial resistance factors in the ST11-KL64 hv-CRKP strain represents a significant challenge for treating immunocompromised pediatric patients. Particularly concerning is the resistance to polymyxin and tigecycline, which are often last-resort treatments for multidrug-resistant infections. The findings highlight the urgent need for effective surveillance, infection control measures, and novel therapeutic strategies to manage such hypervirulent and multidrug-resistant pathogens.</p>\",\"PeriodicalId\":12637,\"journal\":{\"name\":\"Frontiers in Pediatrics\",\"volume\":\"12 \",\"pages\":\"1450201\"},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2025-01-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743731/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Pediatrics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3389/fped.2024.1450201\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"PEDIATRICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Pediatrics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fped.2024.1450201","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"PEDIATRICS","Score":null,"Total":0}
引用次数: 0
摘要
高毒力耐碳青霉烯肺炎克雷伯菌（hv-CRKP）由于其高治疗难度和相关死亡率，特别是在骨髓移植（BMT）患者中，造成了越来越大的公共卫生风险。具有多种耐药机制的菌株的出现使这些感染的管理进一步复杂化。方法：我们从一名儿童骨髓移植患者中分离出一株新的ST11-KL64 hv-CRKP菌株并对其进行鉴定。进行药敏试验以确定耐药模式。研究人员进行了全面的基因组分析，以确定质粒类型、毒力因子和抗菌耐药基因，以及与突变和质粒介导的变异相关的潜在耐药机制。结果：分离的hv-CRKP菌株对碳青霉烯类、替加环素和多粘菌素均表现出多重耐药。基因组分析显示，IncHI1B/repB质粒携带毒力因子（rmpA、ΔrmpA2、iucABCD、iutA），而IncFII/IncR和IncFII质粒携带抗性基因[bla C T X - M - 6.5、bla T E M - 1b、rmtB、bla S H V - 12、bla K P - 2、qnrS1、bla L A P - 2、sul2、dfrA14、tet(A)、tet(R)]。在一个hv-CRKP菌株中同时存在bla C T X - M - 65、bla T E M - 1b、bla S H V - 12、bla L A P - 2和bla KP C - 2的情况极为罕见。此外，缀合质粒pTET-4中的Tet(A)-S251A变体可能赋予替加环素耐药性。MgrB、PhoPQ和PmrABCDK突变被确定为增加多粘菌素耐药性的潜在因素。有趣的是，质粒编码的限制性修饰系统和逆转录区被鉴定出来，这可能会赋予噬菌体耐药性。讨论：ST11-KL64 hv-CRKP菌株的毒力和抗菌耐药因素的结合对治疗免疫功能低下的儿科患者来说是一个重大挑战。尤其令人担忧的是对多粘菌素和替加环素的耐药性，这两种药物通常是治疗耐多药感染的最后手段。这些发现突出表明，迫切需要有效的监测、感染控制措施和新的治疗策略来管理这种高毒力和多重耐药病原体。
Multidrug-resistant ST11-KL64 hypervirulent Klebsiella pneumoniae with multiple bla- genes isolated from children's blood.
Introduction: Hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) poses an increasing public health risk due to its high treatment difficulty and associated mortality, especially in bone marrow transplant (BMT) patients. The emergence of strains with multiple resistance mechanisms further complicates the management of these infections.
Methods: We isolated and characterized a novel ST11-KL64 hv-CRKP strain from a pediatric bone marrow transplantation patient. Antimicrobial susceptibility testing was performed to determine resistance patterns. Comprehensive genomic analysis was conducted to identify plasmid types, virulence factors, and antimicrobial resistance genes, as well as potential resistance mechanisms associated with mutations and plasmid-mediated variants.
Results: The isolated hv-CRKP strain exhibited multidrug resistance to carbapenem, tigecycline, and polymyxin. Genomic analysis revealed that the IncHI1B/repB plasmid carried virulence factors (rmpA, ΔrmpA2, iucABCD, iutA), while IncFII/IncR and IncFII plasmids harbored resistance genes [blaCTX-M-65, blaTEM-1B, rmtB, blaSHV-12, blaKPC-2, qnrS1, blaLAP-2, sul2, dfrA14, tet(A), tet(R)]. The coexistence of blaCTX-M-65, blaTEM-1B, blaSHV-12, blaLAP-2,and blaKPC-2 in one hv-CRKP strain is exceptionally rare. Additionally, the Tet(A)-S251A variant in the conjugative plasmid pTET-4 may confer tigecycline resistance. Mutations in MgrB, PhoPQ, and PmrABCDK were identified as potential contributors to increased polymyxin resistance. Interestingly, plasmid-encoded restriction-modification systems and Retron regions were identified, which could potentially confer phage resistance.
Discussion: The combination of virulence and antimicrobial resistance factors in the ST11-KL64 hv-CRKP strain represents a significant challenge for treating immunocompromised pediatric patients. Particularly concerning is the resistance to polymyxin and tigecycline, which are often last-resort treatments for multidrug-resistant infections. The findings highlight the urgent need for effective surveillance, infection control measures, and novel therapeutic strategies to manage such hypervirulent and multidrug-resistant pathogens.
期刊介绍：
Frontiers in Pediatrics (Impact Factor 2.33) publishes rigorously peer-reviewed research broadly across the field, from basic to clinical research that meets ongoing challenges in pediatric patient care and child health. Field Chief Editors Arjan Te Pas at Leiden University and Michael L. Moritz at the Children''s Hospital of Pittsburgh are 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 Pediatrics also features Research Topics, Frontiers special theme-focused issues managed by Guest Associate Editors, addressing important areas in pediatrics. In this fashion, Frontiers serves as an outlet to publish the broadest aspects of pediatrics in both basic and clinical research, including high-quality reviews, case reports, editorials and commentaries related to all aspects of pediatrics.
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