Multidrug-resistant ST11-KL64 hypervirulent Klebsiella pneumoniae with multiple bla- genes isolated from children's blood

IntroductionHypervirulent 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 furth...

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Main Authors: Rongmu Luo, Guannan Ma, Qian Yu, Zhengqin Tian, Qihang Man, Xiangrong Shu, Xuetong Liu, Yupeng Shi, Lei Zhang, Jingbo Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Pediatrics
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Online Access:https://www.frontiersin.org/articles/10.3389/fped.2024.1450201/full
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author Rongmu Luo
Rongmu Luo
Guannan Ma
Qian Yu
Zhengqin Tian
Qihang Man
Xiangrong Shu
Xuetong Liu
Yupeng Shi
Lei Zhang
Jingbo Wang
author_facet Rongmu Luo
Rongmu Luo
Guannan Ma
Qian Yu
Zhengqin Tian
Qihang Man
Xiangrong Shu
Xuetong Liu
Yupeng Shi
Lei Zhang
Jingbo Wang
author_sort Rongmu Luo
collection DOAJ
description IntroductionHypervirulent 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.MethodsWe 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.ResultsThe 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.DiscussionThe 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.
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spelling doaj-art-12a895a3e275406f904e06917c80f3d02025-01-06T06:59:16ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602025-01-011210.3389/fped.2024.14502011450201Multidrug-resistant ST11-KL64 hypervirulent Klebsiella pneumoniae with multiple bla- genes isolated from children's bloodRongmu Luo0Rongmu Luo1Guannan Ma2Qian Yu3Zhengqin Tian4Qihang Man5Xiangrong Shu6Xuetong Liu7Yupeng Shi8Lei Zhang9Jingbo Wang10Department of Hematology, Aerospace Center Hospital, Beijing, ChinaDepartment of Hematology, China Aerospace Science & Industry Corporation 731 Hospital, Beijing, ChinaMedical Research Center, Key Laboratory of Digital Technology in Medical Diagnostics of Zhejiang Province, Hangzhou, ChinaMedical Research Center, Key Laboratory of Digital Technology in Medical Diagnostics of Zhejiang Province, Hangzhou, ChinaDepartment of Hematology, Aerospace Center Hospital, Beijing, ChinaDepartment of Hematology, Aerospace Center Hospital, Beijing, ChinaDepartment of Hematology, China Aerospace Science & Industry Corporation 731 Hospital, Beijing, ChinaMedical Research Center, Key Laboratory of Digital Technology in Medical Diagnostics of Zhejiang Province, Hangzhou, ChinaMedical Research Center, Key Laboratory of Digital Technology in Medical Diagnostics of Zhejiang Province, Hangzhou, ChinaMedical Research Center, Key Laboratory of Digital Technology in Medical Diagnostics of Zhejiang Province, Hangzhou, ChinaDepartment of Hematology, Aerospace Center Hospital, Beijing, ChinaIntroductionHypervirulent 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.MethodsWe 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.ResultsThe 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.DiscussionThe 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.https://www.frontiersin.org/articles/10.3389/fped.2024.1450201/fullhv-CRKPpolymyxintigecyclinecarbapenemBMT
spellingShingle Rongmu Luo
Rongmu Luo
Guannan Ma
Qian Yu
Zhengqin Tian
Qihang Man
Xiangrong Shu
Xuetong Liu
Yupeng Shi
Lei Zhang
Jingbo Wang
Multidrug-resistant ST11-KL64 hypervirulent Klebsiella pneumoniae with multiple bla- genes isolated from children's blood
Frontiers in Pediatrics
hv-CRKP
polymyxin
tigecycline
carbapenem
BMT
title Multidrug-resistant ST11-KL64 hypervirulent Klebsiella pneumoniae with multiple bla- genes isolated from children's blood
title_full Multidrug-resistant ST11-KL64 hypervirulent Klebsiella pneumoniae with multiple bla- genes isolated from children's blood
title_fullStr Multidrug-resistant ST11-KL64 hypervirulent Klebsiella pneumoniae with multiple bla- genes isolated from children's blood
title_full_unstemmed Multidrug-resistant ST11-KL64 hypervirulent Klebsiella pneumoniae with multiple bla- genes isolated from children's blood
title_short Multidrug-resistant ST11-KL64 hypervirulent Klebsiella pneumoniae with multiple bla- genes isolated from children's blood
title_sort multidrug resistant st11 kl64 hypervirulent klebsiella pneumoniae with multiple bla genes isolated from children s blood
topic hv-CRKP
polymyxin
tigecycline
carbapenem
BMT
url https://www.frontiersin.org/articles/10.3389/fped.2024.1450201/full
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