Comparison of Two Distinct Subpopulations of Klebsiella pneumoniae ST16 Co-Occurring in a Single Patient

ABSTRACT The higher resistance rate to ceftazidime-avibactam (CZA) is mainly related to carbapenem resistance, especially New Delhi metallo-β-lactamase (NDM). The CZA-susceptible Klebsiella pneumoniae (K191663) and the later CZA-resistant isolates (K191724, K191725, K191773) co-producing NDM-4 and O...

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Main Authors: Biying Zhang, Renjing Hu, Qinghua Liang, Shuang Liang, Qin Li, Jiawei Bai, Manlin Ding, Feiyang Zhang, Yingshun Zhou
Format: Article
Language:English
Published: American Society for Microbiology 2022-06-01
Series:Microbiology Spectrum
Subjects:
Online Access:https://journals.asm.org/doi/10.1128/spectrum.02624-21
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author Biying Zhang
Renjing Hu
Qinghua Liang
Shuang Liang
Qin Li
Jiawei Bai
Manlin Ding
Feiyang Zhang
Yingshun Zhou
author_facet Biying Zhang
Renjing Hu
Qinghua Liang
Shuang Liang
Qin Li
Jiawei Bai
Manlin Ding
Feiyang Zhang
Yingshun Zhou
author_sort Biying Zhang
collection DOAJ
description ABSTRACT The higher resistance rate to ceftazidime-avibactam (CZA) is mainly related to carbapenem resistance, especially New Delhi metallo-β-lactamase (NDM). The CZA-susceptible Klebsiella pneumoniae (K191663) and the later CZA-resistant isolates (K191724, K191725, K191773) co-producing NDM-4 and OXA-181 were obtained from the same hospitalized patient returning from Vietnam. Our study aims to elucidate the diversity of K. pneumoniae ST16 through comparative analysis of whole-genome sequencing (WGS) data and identify the potential evolution of plasmids by sequencing longitudinal clinical isolates during antibiotic treatment. Firstly, multilocus sequence typing analysis and phylogenic analysis suggested that these strains belong to the two lineages of K. pneumoniae ST16. Surprisingly, the CZA-resistant strains were closely related to K. pneumoniae ST16 described in South Korea, instead of the blaNDM-4- or blaOXA-181-carrying ST16 reported in Vietnam. Secondly, blaNDM-4, blaTEM-1B, and rmtB co-existed on a self-conjugative IncFII(Yp)-like plasmid, which played a significant role in CZA resistance. It could transfer into the recipient Escherichia coli J53 at high frequency, indicating the risk of mobile carbapenemases. In addition, the loss of 12-kbp fragment occurred in blaNDM-4-positive isolate (K191773), which was likely caused by insertion sequence-mediated homologous recombination. Last but not least, as a repressor of acrAB operon system, acrR was truncated by a frameshift mutation in K191663. Thus, our study provided baseline information for monitoring the occurrence and development of bacterial resistance. IMPORTANCE As a leading health care-acquired infection pathogen, Klebsiella pneumoniae is threatening a large number of inpatients due to its diverse antibiotic resistance and virulence factors. Heretofore, with a growing number of reports about the coexistence of several carbapenemases in carbapenem-resistant K. pneumoniae (CRKP), epidemiologic surveillance has been strengthened. Nevertheless, the nosocomial outbreaks by CRKP ST16 are gradually increasing worldwide. Our study provides a deeper insight into the diversification of clinical isolates of CRKP ST16 in China. In addition, the comparison analysis of resistant plasmids may reveal the transmission of carbapenemase-encoding genes. Furthermore, our study also highlights the importance of longitudinal specimen collection and continuous monitoring during the treatment, which play a crucial role in understanding the development of antibiotic resistance and the evolution of resistance plasmids.
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spelling doaj.art-40efe762c63e41a4b57e313027a6cf362022-12-22T03:32:54ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972022-06-0110310.1128/spectrum.02624-21Comparison of Two Distinct Subpopulations of Klebsiella pneumoniae ST16 Co-Occurring in a Single PatientBiying Zhang0Renjing Hu1Qinghua Liang2Shuang Liang3Qin Li4Jiawei Bai5Manlin Ding6Feiyang Zhang7Yingshun Zhou8Department of Pathogenic Biology, School of Basic Medicine, Southwest Medical University, Luzhou, Sichuan, ChinaDepartment of Laboratory Medicine, The Affiliated Wuxi No.2 People’s Hospital of Nanjing Medical University, Wuxi, Jiangsu, ChinaDepartment of Pathogenic Biology, School of Basic Medicine, Southwest Medical University, Luzhou, Sichuan, ChinaDepartment of Pathogenic Biology, School of Basic Medicine, Southwest Medical University, Luzhou, Sichuan, ChinaDepartment of Pathogenic Biology, School of Basic Medicine, Southwest Medical University, Luzhou, Sichuan, ChinaDepartment of Pathogenic Biology, School of Basic Medicine, Southwest Medical University, Luzhou, Sichuan, ChinaDepartment of Pathogenic Biology, School of Basic Medicine, Southwest Medical University, Luzhou, Sichuan, ChinaDepartment of Pathogenic Biology, School of Basic Medicine, Southwest Medical University, Luzhou, Sichuan, ChinaDepartment of Pathogenic Biology, School of Basic Medicine, Southwest Medical University, Luzhou, Sichuan, ChinaABSTRACT The higher resistance rate to ceftazidime-avibactam (CZA) is mainly related to carbapenem resistance, especially New Delhi metallo-β-lactamase (NDM). The CZA-susceptible Klebsiella pneumoniae (K191663) and the later CZA-resistant isolates (K191724, K191725, K191773) co-producing NDM-4 and OXA-181 were obtained from the same hospitalized patient returning from Vietnam. Our study aims to elucidate the diversity of K. pneumoniae ST16 through comparative analysis of whole-genome sequencing (WGS) data and identify the potential evolution of plasmids by sequencing longitudinal clinical isolates during antibiotic treatment. Firstly, multilocus sequence typing analysis and phylogenic analysis suggested that these strains belong to the two lineages of K. pneumoniae ST16. Surprisingly, the CZA-resistant strains were closely related to K. pneumoniae ST16 described in South Korea, instead of the blaNDM-4- or blaOXA-181-carrying ST16 reported in Vietnam. Secondly, blaNDM-4, blaTEM-1B, and rmtB co-existed on a self-conjugative IncFII(Yp)-like plasmid, which played a significant role in CZA resistance. It could transfer into the recipient Escherichia coli J53 at high frequency, indicating the risk of mobile carbapenemases. In addition, the loss of 12-kbp fragment occurred in blaNDM-4-positive isolate (K191773), which was likely caused by insertion sequence-mediated homologous recombination. Last but not least, as a repressor of acrAB operon system, acrR was truncated by a frameshift mutation in K191663. Thus, our study provided baseline information for monitoring the occurrence and development of bacterial resistance. IMPORTANCE As a leading health care-acquired infection pathogen, Klebsiella pneumoniae is threatening a large number of inpatients due to its diverse antibiotic resistance and virulence factors. Heretofore, with a growing number of reports about the coexistence of several carbapenemases in carbapenem-resistant K. pneumoniae (CRKP), epidemiologic surveillance has been strengthened. Nevertheless, the nosocomial outbreaks by CRKP ST16 are gradually increasing worldwide. Our study provides a deeper insight into the diversification of clinical isolates of CRKP ST16 in China. In addition, the comparison analysis of resistant plasmids may reveal the transmission of carbapenemase-encoding genes. Furthermore, our study also highlights the importance of longitudinal specimen collection and continuous monitoring during the treatment, which play a crucial role in understanding the development of antibiotic resistance and the evolution of resistance plasmids.https://journals.asm.org/doi/10.1128/spectrum.02624-21carbapenemase-producing Klebsiella pneumoniaeST16NDM-4OXA-181ceftazidime–avibactamIS26
spellingShingle Biying Zhang
Renjing Hu
Qinghua Liang
Shuang Liang
Qin Li
Jiawei Bai
Manlin Ding
Feiyang Zhang
Yingshun Zhou
Comparison of Two Distinct Subpopulations of Klebsiella pneumoniae ST16 Co-Occurring in a Single Patient
Microbiology Spectrum
carbapenemase-producing Klebsiella pneumoniae
ST16
NDM-4
OXA-181
ceftazidime–avibactam
IS26
title Comparison of Two Distinct Subpopulations of Klebsiella pneumoniae ST16 Co-Occurring in a Single Patient
title_full Comparison of Two Distinct Subpopulations of Klebsiella pneumoniae ST16 Co-Occurring in a Single Patient
title_fullStr Comparison of Two Distinct Subpopulations of Klebsiella pneumoniae ST16 Co-Occurring in a Single Patient
title_full_unstemmed Comparison of Two Distinct Subpopulations of Klebsiella pneumoniae ST16 Co-Occurring in a Single Patient
title_short Comparison of Two Distinct Subpopulations of Klebsiella pneumoniae ST16 Co-Occurring in a Single Patient
title_sort comparison of two distinct subpopulations of klebsiella pneumoniae st16 co occurring in a single patient
topic carbapenemase-producing Klebsiella pneumoniae
ST16
NDM-4
OXA-181
ceftazidime–avibactam
IS26
url https://journals.asm.org/doi/10.1128/spectrum.02624-21
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