Prevalence and molecular characteristics of colistin-resistant isolates among carbapenem-resistant Klebsiella pneumoniae in Central South China: a multicenter study

Abstract Background The emergence of colistin resistance in carbapenem-resistant Klebsiella pneumoniae (CRKP) is a significant public health concern, as colistin has been the last resort for treating such infections. This study aimed to investigate the prevalence and molecular characteristics of col...

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Main Authors: Zijuan Jian, Yanjun Liu, Zhiqian Wang, Peilin Liu, Jiahui Wang, Qun Yan, Wenen Liu
Format: Article
Language:English
Published: BMC 2025-01-01
Series:Annals of Clinical Microbiology and Antimicrobials
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Online Access:https://doi.org/10.1186/s12941-024-00769-1
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author Zijuan Jian
Yanjun Liu
Zhiqian Wang
Peilin Liu
Jiahui Wang
Qun Yan
Wenen Liu
author_facet Zijuan Jian
Yanjun Liu
Zhiqian Wang
Peilin Liu
Jiahui Wang
Qun Yan
Wenen Liu
author_sort Zijuan Jian
collection DOAJ
description Abstract Background The emergence of colistin resistance in carbapenem-resistant Klebsiella pneumoniae (CRKP) is a significant public health concern, as colistin has been the last resort for treating such infections. This study aimed to investigate the prevalence and molecular characteristics of colistin-resistant CRKP isolates in Central South China. Methods CRKP isolates from twelve hospitals in Central South China were screened for colistin resistance using broth microdilution. The epidemiological characteristics, virulome, resistome, plasmid replicons and two-component systems associated with colistin resistance of colistin-resistant isolates were explored by whole-genome sequencing. The mgrB gene and the relative expression of the pmrC and pmrK genes were analyzed by polymerase chain reaction (PCR) and real-time quantitative PCR, respectively. The bacterial virulence was evaluated through a Galleria mellonella larvae infection model. Results Of the 429 nonduplicate CRKP isolates, 26 (6.1%) were colistin-resistant and they included eight clonal clusters. Six distinct sequence type (ST)-capsule loci (KL) types were identified: ST11-KL64, ST11-KL47, ST963-KL16, ST307-KL102, ST751-KL64 and ST5254-KL47. 88.5% (23/26) of them were found to carry at least one carbapenemase gene, including bla KPC−2 (65.4%, 17/26) and bla NDM−1 (7.7%, 2/26), as well as coharbouring bla KPC−2 and bla NDM−1 (15.4%, 4/26). Diverse mutations of colistin resistance-related genes were observed, with mgrB inactivation by insertions and the T157P deleterious mutation in pmrB being detected in 57.7% and 42.3% of the colistin-resistant isolates, respectively. In addition, a novel deleterious mutation, R248P, in the crrB gene was found in two ST11 isolates. 88.5% of the 26 isolates presented an increase in pmrK transcription, and 69.2% of them had an overexpression of the pmrC gene. All the 16 ST11-KL64 isolates and one ST751-KL64 isolate (65.4%, 17/26) carried at least two hypervirulence biomarkers and showed high virulence in vivo. Conclusions This study highlights the presence of different colistin resistance mechanisms in isolates belonging to the same clone and identified multiple clonal transmission clusters in colistin resistant isolates, including the globally high-risk ST11 and ST307 clones, of which a significant proportion exhibited high virulence. Consequently, it is crucial to enforce measures to prevent the ongoing spread of colistin resistance.
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spelling doaj-art-92ede413659c4aca92b405f0114680bf2025-01-05T12:11:00ZengBMCAnnals of Clinical Microbiology and Antimicrobials1476-07112025-01-0124111410.1186/s12941-024-00769-1Prevalence and molecular characteristics of colistin-resistant isolates among carbapenem-resistant Klebsiella pneumoniae in Central South China: a multicenter studyZijuan Jian0Yanjun Liu1Zhiqian Wang2Peilin Liu3Jiahui Wang4Qun Yan5Wenen Liu6Department of Clinical Laboratory, Xiangya Hospital, Central South UniversityDepartment of Clinical Laboratory, Xiangya Hospital, Central South UniversityDepartment of Clinical Laboratory, Xiangya Hospital, Central South UniversityDepartment of Clinical Laboratory, Xiangya Hospital, Central South UniversityDepartment of Clinical Laboratory, Xiangya Hospital, Central South UniversityDepartment of Clinical Laboratory, Xiangya Hospital, Central South UniversityDepartment of Clinical Laboratory, Xiangya Hospital, Central South UniversityAbstract Background The emergence of colistin resistance in carbapenem-resistant Klebsiella pneumoniae (CRKP) is a significant public health concern, as colistin has been the last resort for treating such infections. This study aimed to investigate the prevalence and molecular characteristics of colistin-resistant CRKP isolates in Central South China. Methods CRKP isolates from twelve hospitals in Central South China were screened for colistin resistance using broth microdilution. The epidemiological characteristics, virulome, resistome, plasmid replicons and two-component systems associated with colistin resistance of colistin-resistant isolates were explored by whole-genome sequencing. The mgrB gene and the relative expression of the pmrC and pmrK genes were analyzed by polymerase chain reaction (PCR) and real-time quantitative PCR, respectively. The bacterial virulence was evaluated through a Galleria mellonella larvae infection model. Results Of the 429 nonduplicate CRKP isolates, 26 (6.1%) were colistin-resistant and they included eight clonal clusters. Six distinct sequence type (ST)-capsule loci (KL) types were identified: ST11-KL64, ST11-KL47, ST963-KL16, ST307-KL102, ST751-KL64 and ST5254-KL47. 88.5% (23/26) of them were found to carry at least one carbapenemase gene, including bla KPC−2 (65.4%, 17/26) and bla NDM−1 (7.7%, 2/26), as well as coharbouring bla KPC−2 and bla NDM−1 (15.4%, 4/26). Diverse mutations of colistin resistance-related genes were observed, with mgrB inactivation by insertions and the T157P deleterious mutation in pmrB being detected in 57.7% and 42.3% of the colistin-resistant isolates, respectively. In addition, a novel deleterious mutation, R248P, in the crrB gene was found in two ST11 isolates. 88.5% of the 26 isolates presented an increase in pmrK transcription, and 69.2% of them had an overexpression of the pmrC gene. All the 16 ST11-KL64 isolates and one ST751-KL64 isolate (65.4%, 17/26) carried at least two hypervirulence biomarkers and showed high virulence in vivo. Conclusions This study highlights the presence of different colistin resistance mechanisms in isolates belonging to the same clone and identified multiple clonal transmission clusters in colistin resistant isolates, including the globally high-risk ST11 and ST307 clones, of which a significant proportion exhibited high virulence. Consequently, it is crucial to enforce measures to prevent the ongoing spread of colistin resistance.https://doi.org/10.1186/s12941-024-00769-1Colistin resistanceCRKPWhole-genome sequencingMgrBHypervirulenceCentral South China
spellingShingle Zijuan Jian
Yanjun Liu
Zhiqian Wang
Peilin Liu
Jiahui Wang
Qun Yan
Wenen Liu
Prevalence and molecular characteristics of colistin-resistant isolates among carbapenem-resistant Klebsiella pneumoniae in Central South China: a multicenter study
Annals of Clinical Microbiology and Antimicrobials
Colistin resistance
CRKP
Whole-genome sequencing
MgrB
Hypervirulence
Central South China
title Prevalence and molecular characteristics of colistin-resistant isolates among carbapenem-resistant Klebsiella pneumoniae in Central South China: a multicenter study
title_full Prevalence and molecular characteristics of colistin-resistant isolates among carbapenem-resistant Klebsiella pneumoniae in Central South China: a multicenter study
title_fullStr Prevalence and molecular characteristics of colistin-resistant isolates among carbapenem-resistant Klebsiella pneumoniae in Central South China: a multicenter study
title_full_unstemmed Prevalence and molecular characteristics of colistin-resistant isolates among carbapenem-resistant Klebsiella pneumoniae in Central South China: a multicenter study
title_short Prevalence and molecular characteristics of colistin-resistant isolates among carbapenem-resistant Klebsiella pneumoniae in Central South China: a multicenter study
title_sort prevalence and molecular characteristics of colistin resistant isolates among carbapenem resistant klebsiella pneumoniae in central south china a multicenter study
topic Colistin resistance
CRKP
Whole-genome sequencing
MgrB
Hypervirulence
Central South China
url https://doi.org/10.1186/s12941-024-00769-1
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