Genome sequencing unveils blaKPC-2-harboring plasmids as drivers of enhanced resistance and virulence in nosocomial Klebsiella pneumoniae

被引:5
作者
Han, Xinhong [1 ,2 ,3 ]
Zhou, Junxin [1 ,2 ,3 ]
Yu, Lifei [4 ]
Shao, Lina [1 ]
Cai, Shiqi [1 ,2 ,3 ]
Hu, Huangdu [1 ,2 ,3 ]
Shi, Qiucheng [1 ,2 ,3 ]
Wang, Zhengan [1 ,2 ,3 ]
Hua, Xiaoting [1 ,2 ,3 ]
Jiang, Yan [1 ,2 ,3 ]
Yu, Yunsong [1 ,2 ,3 ]
机构
[1] Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Infect Dis, Sch Med, Hangzhou, Peoples R China
[2] Key Lab Microbial Technol & Bioinformat Zhejiang P, Hangzhou, Peoples R China
[3] Zhejiang Univ, Sir Run Run Shaw Hosp, Natl Inst Resp Dis, Reg Med Ctr,Sch Med, Hangzhou, Peoples R China
[4] Zhejiang Univ, Affiliated Hangzhou Peoples Hosp 1, Dept Infect Dis, Sch Med, Hangzhou, Peoples R China
基金
中国国家自然科学基金;
关键词
carbapenem-resistant K. pneumoniae; KPC-2; carbapenemase; long-read sequencing; plasmid evolution; novel beta-lactam/beta-lactamase inhibitor combinations;
D O I
10.1128/msystems.00924-23
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The threat posed by Klebsiella pneumoniae in healthcare settings has worsened due to the evolutionary advantages conferred by blaKPC-2-harboring plasmids (pKPC-2). However, the specific evolutionary pathway of nosocomial K. pneumoniae carrying pKPC-2 and its transmission between patients and healthcare environments are not yet well understood. Between 1 August and 31 December 2019, 237 ST11 KPC-2-producing-carbapenem-resistant K. pneumoniae (CRKP) (KPC-2-CRKP) were collected from patient or ward environments in an intensive care unit and subjected to Illumina sequencing, of which 32 strains were additionally selected for Nanopore sequencing to obtain complete plasmid sequences. Bioinformatics analysis, conjugation experiments, antimicrobial susceptibility tests, and virulence assays were performed to identify the evolutionary characteristics of pKPC-2. The pKPC-2 plasmids were divided into three subgroups with distinct evolutionary events, including Tn3-mediated plasmid homologous recombination, IS26-mediated horizontal gene transfer, and dynamic duplications of antibiotic resistance genes (ARGs). Surprisingly, the incidence rates of multicopy blaKPC-2, blaSHV-12, and blaCTX-M-65 were quite high (ranging from 27.43% to 67.01%), and strains negative for extended-spectrum beta-lactamase tended to develop multicopy blaKPC-2. Notably, the presence of multicopy blaSHV-12 reduced sensitivity to ceftazidime/avibactam (CZA), and the relative expression level of blaSHV-12 in the CZA-resistant group was 6.12 times higher than that in the sensitive group. Furthermore, a novel hybrid pKPC-2 was identified, presenting enhanced virulence levels and decreased susceptibility to CZA. This study emphasizes the notable prevalence of multicopy ARGs and provides a comprehensive insight into the intricate and diverse evolutionary pathways of resistant plasmids that disseminate among patients and healthcare environments.
引用
收藏
页数:16
相关论文
共 45 条
  • [1] [Anonymous], 2015, Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically
  • [2] [Anonymous], 2020, Clinical Laboratory Standards Institute: CLSI Guidelines
  • [3] Beyond microbial core genomic epidemiology: towards pan genomic epidemiology Comment
    Castillo-Ramirez, Santiago
    [J]. LANCET MICROBE, 2022, 3 (04): : E244 - E245
  • [4] Multi-institute analysis of carbapenem resistance reveals remarkable diversity, unexplained mechanisms, and limited clonal outbreaks
    Cerqueira, Gustavo C.
    Earl, Ashlee M.
    Ernst, Christoph M.
    Grad, Yonatan H.
    Dekker, John P.
    Feldgarden, Michael
    Chapman, Sinead B.
    Reis-Cunha, Joao L.
    Shea, Terrance P.
    Young, Sarah
    Zeng, Qiandong
    Delaney, Mary L.
    Kim, Diane
    Peterson, Ellena M.
    O'Brien, Thomas F.
    Ferraro, Mary Jane
    Hooper, David C.
    Huang, Susan S.
    Kirby, James E.
    Onderdonk, Andrew B.
    Birren, Bruce W.
    Hung, Deborah T.
    Cosimi, Lisa A.
    Wortman, Jennifer R.
    Murphy, Cheryl I.
    Hanage, William P.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2017, 114 (05) : 1135 - 1140
  • [5] Delineation of ISEcp1 and IS26-Mediated Plasmid Fusion Processes by MinION Single-Molecule Long-Read Sequencing
    Chen, Kaichao
    Xie, Miaomiao
    Chan, Edward Wai-Chi
    Chen, Sheng
    [J]. FRONTIERS IN MICROBIOLOGY, 2022, 12
  • [6] Integrated chromosomal and plasmid sequence analyses reveal diverse modes of carbapenemase gene spread among Klebsiella pneumoniae
    David, Sophia
    Cohen, Victoria
    Reuter, Sandra
    Sheppard, Anna E.
    Giani, Tommaso
    Parkhill, Julian
    Rossolini, Gian Maria
    Feil, Edward J.
    Grundmann, Hajo
    Aanensen, David M.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2020, 117 (40) : 25043 - 25054
  • [7] Pandemic spread of blaKPC-2 among Klebsiella pneumoniae ST11 in China is associated with horizontal transfer mediated by IncFII-like plasmids
    Fu, Pan
    Tang, Yu
    Li, Gang
    Yu, Lianhua
    Wang, Yong
    Jiang, Xiaofei
    [J]. INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, 2019, 54 (02) : 117 - 124
  • [8] The transferability and evolution of NDM-1 and KPC-2 co-producing Klebsiella pneumoniae from clinical settings
    Gao, Hua
    Liu, Yudong
    Wang, Ruobing
    Wang, Qi
    Jin, Longyang
    Wang, Hui
    [J]. EBIOMEDICINE, 2020, 51
  • [9] Epidemiological Characteristics of OXA-232-Producing Carbapenem-Resistant Klebsiella pneumoniae Strains Isolated during Nosocomial Clonal Spread Associated with Environmental Colonization
    Han, Xinhong
    Chen, Ying
    Zhou, Junxin
    Shi, Qiucheng
    Jiang, Yan
    Wu, Xueqing
    Quan, Jingjing
    Hu, Huangdu
    Wang, Qian
    Yu, Yunsong
    Fu, Ying
    [J]. MICROBIOLOGY SPECTRUM, 2022, 10 (04):
  • [10] Emergence of Ceftazidime/Avibactam and Tigecycline Resistance in Carbapenem-Resistant Klebsiella pneumoniae Due to In-Host Microevolution
    Han, Xinhong
    Shi, Qiucheng
    Mao, Yihan
    Quan, Jingjing
    Zhang, Ping
    Lan, Peng
    Jiang, Yan
    Zhao, Dongdong
    Wu, Xueqing
    Hua, Xiaoting
    Yu, Yunsong
    [J]. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, 2021, 11