Skip to main content
Top
Published in: BMC Infectious Diseases 1/2020

Open Access 01-12-2020 | Expectoration | Research article

Outbreak of KPC-2 Carbapenem-resistant Klebsiella pneumoniae ST76 and Carbapenem-resistant K2 Hypervirulent Klebsiella pneumoniae ST375 strains in Northeast China: molecular and virulent characteristics

Authors: Shanshan Su, Jisheng Zhang, Yongxin Zhao, Lan Yu, Yong Wang, Yuchao Wang, Mingjia Bao, Yu Fu, Chunjiang Li, Xiaoli Zhang

Published in: BMC Infectious Diseases | Issue 1/2020

Login to get access

Abstract

Background

Carbapenem-resistant hypervirulent Klebsiella pneumoniae strains have recently come into existence worldwide; however, researchers in northeast China are not aware of their clinical features and molecular characteristics.

Methods

Here, the molecular and virulent characteristics of 44 carbapenem-resistant K. pneumoniae (CRKP) isolates collected from January 2015 to December 2017 were studied. Multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were carried out to define the clonal relatedness among the isolates. PCR and capsular serotyping of the virulence-associated genes, as well as biofilm formation and serum complement-mediated killing assays, were employed to determine the virulent potential. The genomic features and associated mobile genetic elements of JmsCRE57 were detected by whole genome sequencing.

Results

The only positive isolate was JmsCRE57, which belonged to the ST375 serotype K2 that expressed uge, mrkD, fimH, kpn, aerobactin and rmpA virulence-associated genes and showed strong biofilm formation and serum sensitivity. Sequencing results showed that the JmsCRE57 genome mainly consisted of a circular chromosome, three antimicrobial resistant plasmids and a virulent plasmid. The antimicrobial resistant plasmid expressing blaKPC-2, blaCTX-M-15, aph(3″)-Ib, aph(6)-Id, qnrB1, aac(3)-IIa, aac(6′)-Ib-cr, blaOXA-1, blaTEM-1B, catB4, sul2, dfrA14 and blaSHV-99. The virulent plasmid belonged to the IncHI1B group, which is mainly composed of mucoid phenotype genes and siderophore-associated genes. The remaining CRKP strains that expressed uge, fimH, mrkD and kpn virulence-associated genes were not successfully typed.

Conclusion

Our results provide new insights on the epidemiology of carbapenem-resistant K2 hypervirulent K. pneumoniae ST375 and CRKP ST76 strains in northeast China, which may help control their future outbreaks.
Literature
1.
go back to reference Guo Y, Wang S, Zhan L, Jin Y, Duan J, Hao Z, Lv J, Qi X, Chen L, Kreiswirth BN, et al. Microbiological and clinical characteristics of Hypermucoviscous Klebsiella pneumoniae isolates associated with invasive infections in China. Front Cell Infect Microbiol. 2017;7:24.PubMedPubMedCentral Guo Y, Wang S, Zhan L, Jin Y, Duan J, Hao Z, Lv J, Qi X, Chen L, Kreiswirth BN, et al. Microbiological and clinical characteristics of Hypermucoviscous Klebsiella pneumoniae isolates associated with invasive infections in China. Front Cell Infect Microbiol. 2017;7:24.PubMedPubMedCentral
2.
go back to reference Zheng B, Dai Y, Liu Y, Shi W, Dai E, Han Y, Zheng D, Yu Y, Li M. Molecular epidemiology and risk factors of Carbapenem-resistant Klebsiella pneumoniae infections in eastern China. Front Microbiol. 2017;8:1061.CrossRef Zheng B, Dai Y, Liu Y, Shi W, Dai E, Han Y, Zheng D, Yu Y, Li M. Molecular epidemiology and risk factors of Carbapenem-resistant Klebsiella pneumoniae infections in eastern China. Front Microbiol. 2017;8:1061.CrossRef
3.
go back to reference Siu LK, Fung CP, Chang FY, Lee N, Yeh KM, Koh TH, Ip M. Molecular typing and virulence analysis of serotype K1 Klebsiella pneumoniae strains isolated from liver abscess patients and stool samples from noninfectious subjects in Hong Kong, Singapore, and Taiwan. J Clin Microbiol. 2011;49(11):3761–5.CrossRef Siu LK, Fung CP, Chang FY, Lee N, Yeh KM, Koh TH, Ip M. Molecular typing and virulence analysis of serotype K1 Klebsiella pneumoniae strains isolated from liver abscess patients and stool samples from noninfectious subjects in Hong Kong, Singapore, and Taiwan. J Clin Microbiol. 2011;49(11):3761–5.CrossRef
4.
go back to reference Yao B, Xiao X, Wang F, Zhou L, Zhang X, Zhang J. Clinical and molecular characteristics of multi-clone carbapenem-resistant hypervirulent (hypermucoviscous) Klebsiella pneumoniae isolates in a tertiary hospital in Beijing, China. Int J Infect Dis. 2015;37:107–12.CrossRef Yao B, Xiao X, Wang F, Zhou L, Zhang X, Zhang J. Clinical and molecular characteristics of multi-clone carbapenem-resistant hypervirulent (hypermucoviscous) Klebsiella pneumoniae isolates in a tertiary hospital in Beijing, China. Int J Infect Dis. 2015;37:107–12.CrossRef
5.
go back to reference Bocanegra-Ibarias P, Garza-Gonzalez E, Morfin-Otero R, Barrios H, Villarreal-Trevino L, Rodriguez-Noriega E, Garza-Ramos U, Petersen-Morfin S, Silva-Sanchez J. Molecular and microbiological report of a hospital outbreak of NDM-1-carrying Enterobacteriaceae in Mexico. PLoS One. 2017;12(6):e0179651.CrossRef Bocanegra-Ibarias P, Garza-Gonzalez E, Morfin-Otero R, Barrios H, Villarreal-Trevino L, Rodriguez-Noriega E, Garza-Ramos U, Petersen-Morfin S, Silva-Sanchez J. Molecular and microbiological report of a hospital outbreak of NDM-1-carrying Enterobacteriaceae in Mexico. PLoS One. 2017;12(6):e0179651.CrossRef
6.
go back to reference Struve C, Roe CC, Stegger M, Stahlhut SG, Hansen DS, Engelthaler DM, Andersen PS, Driebe EM, Keim P, Krogfelt KA. Mapping the Evolution of Hypervirulent Klebsiella pneumoniae. mBio. 2015;6(4):e00630.CrossRef Struve C, Roe CC, Stegger M, Stahlhut SG, Hansen DS, Engelthaler DM, Andersen PS, Driebe EM, Keim P, Krogfelt KA. Mapping the Evolution of Hypervirulent Klebsiella pneumoniae. mBio. 2015;6(4):e00630.CrossRef
7.
go back to reference Liu Y, Liu PP, Wang LH, Wei DD, Wan LG, Zhang W. Capsular polysaccharide types and virulence-related traits of epidemic KPC-producing Klebsiella pneumoniae isolates in a Chinese University hospital. Microb Drug Resist. 2017;23(7):901–7.CrossRef Liu Y, Liu PP, Wang LH, Wei DD, Wan LG, Zhang W. Capsular polysaccharide types and virulence-related traits of epidemic KPC-producing Klebsiella pneumoniae isolates in a Chinese University hospital. Microb Drug Resist. 2017;23(7):901–7.CrossRef
8.
go back to reference Diago-Navarro E, Chen L, Passet V, Burack S, Ulacia-Hernando A, Kodiyanplakkal RP, Levi MH, Brisse S, Kreiswirth BN, Fries BC. Carbapenem-resistant Klebsiella pneumoniae exhibit variability in capsular polysaccharide and capsule associated virulence traits. J Infect Dis. 2014;210(5):803–13.CrossRef Diago-Navarro E, Chen L, Passet V, Burack S, Ulacia-Hernando A, Kodiyanplakkal RP, Levi MH, Brisse S, Kreiswirth BN, Fries BC. Carbapenem-resistant Klebsiella pneumoniae exhibit variability in capsular polysaccharide and capsule associated virulence traits. J Infect Dis. 2014;210(5):803–13.CrossRef
9.
go back to reference Yang Z, Liu W, Cui Q, Niu W, Li H, Zhao X, Wei X, Wang X, Huang S, Dong D, et al. Prevalence and detection of Stenotrophomonas maltophilia carrying metallo-beta-lactamase blaL1 in Beijing, China. Front Microbiol. 2014;5:692.PubMedPubMedCentral Yang Z, Liu W, Cui Q, Niu W, Li H, Zhao X, Wei X, Wang X, Huang S, Dong D, et al. Prevalence and detection of Stenotrophomonas maltophilia carrying metallo-beta-lactamase blaL1 in Beijing, China. Front Microbiol. 2014;5:692.PubMedPubMedCentral
10.
go back to reference Gu D, Dong N, Zheng Z, Lin D, Huang M, Wang L, Chan EW-C, Shu L, Yu J, Zhang R, et al. A fatal outbreak of ST11 carbapenem-resistant hypervirulent Klebsiella pneumoniae in a Chinese hospital: a molecular epidemiological study. Lancet Infect Dis. 2018;18(1):37–46.CrossRef Gu D, Dong N, Zheng Z, Lin D, Huang M, Wang L, Chan EW-C, Shu L, Yu J, Zhang R, et al. A fatal outbreak of ST11 carbapenem-resistant hypervirulent Klebsiella pneumoniae in a Chinese hospital: a molecular epidemiological study. Lancet Infect Dis. 2018;18(1):37–46.CrossRef
11.
go back to reference Gong X, Zhang J, Su S, Fu Y, Bao M, Wang Y, Zhang X. Molecular characterization and epidemiology of carbapenem non-susceptible Enterobacteriaceae isolated from the eastern region of Heilongjiang Province, China. BMC Infect Dis. 2018;18(1):417.CrossRef Gong X, Zhang J, Su S, Fu Y, Bao M, Wang Y, Zhang X. Molecular characterization and epidemiology of carbapenem non-susceptible Enterobacteriaceae isolated from the eastern region of Heilongjiang Province, China. BMC Infect Dis. 2018;18(1):417.CrossRef
12.
go back to reference Liang Y, Yin X, Zeng L, Chen S. Clonal replacement of epidemic KPC-producing Klebsiella pneumoniae in a hospital in China. BMC Infect Dis. 2017;17(1):363.CrossRef Liang Y, Yin X, Zeng L, Chen S. Clonal replacement of epidemic KPC-producing Klebsiella pneumoniae in a hospital in China. BMC Infect Dis. 2017;17(1):363.CrossRef
13.
go back to reference Fang CT, Lai SY, Yi WC, Hsueh PR, Liu KL, Chang SC. Klebsiella pneumoniae genotype K1: an emerging pathogen that causes septic ocular or central nervous system complications from pyogenic liver abscess. Clin Infect Dis. 2007;45(3):284–93.CrossRef Fang CT, Lai SY, Yi WC, Hsueh PR, Liu KL, Chang SC. Klebsiella pneumoniae genotype K1: an emerging pathogen that causes septic ocular or central nervous system complications from pyogenic liver abscess. Clin Infect Dis. 2007;45(3):284–93.CrossRef
14.
go back to reference Fu L, Huang M, Zhang X, Yang X, Liu Y, Zhang L, Zhang Z, Wang G, Zhou Y. Frequency of virulence factors in high biofilm formation blaKPC-2 producing Klebsiella pneumoniae strains from hospitals. Microb Pathog. 2018;116:168–72.CrossRef Fu L, Huang M, Zhang X, Yang X, Liu Y, Zhang L, Zhang Z, Wang G, Zhou Y. Frequency of virulence factors in high biofilm formation blaKPC-2 producing Klebsiella pneumoniae strains from hospitals. Microb Pathog. 2018;116:168–72.CrossRef
15.
go back to reference El Fertas-Aissani R, Messai Y, Alouache S, Bakour R. Virulence profiles and antibiotic susceptibility patterns of Klebsiella pneumoniae strains isolated from different clinical specimens. Pathologie-biologie. 2013;61(5):209–16.CrossRef El Fertas-Aissani R, Messai Y, Alouache S, Bakour R. Virulence profiles and antibiotic susceptibility patterns of Klebsiella pneumoniae strains isolated from different clinical specimens. Pathologie-biologie. 2013;61(5):209–16.CrossRef
16.
go back to reference Jian-Li W, Yuan-Yuan S, Shou-Yu G, Fei-Fei D, Jia-Yu Y, Xue-Hua W, Yong-Feng Z, Shi-Jin J, Zhi-Jing X. Serotype and virulence genes of Klebsiella pneumoniae isolated from mink and its pathogenesis in mice and mink. Sci Rep. 2017;7(1):17291.CrossRef Jian-Li W, Yuan-Yuan S, Shou-Yu G, Fei-Fei D, Jia-Yu Y, Xue-Hua W, Yong-Feng Z, Shi-Jin J, Zhi-Jing X. Serotype and virulence genes of Klebsiella pneumoniae isolated from mink and its pathogenesis in mice and mink. Sci Rep. 2017;7(1):17291.CrossRef
17.
go back to reference Podschun R, Sievers D, Fischer A, Ullmann U. Serotypes, hemagglutinins, siderophore synthesis, and serum resistance of Klebsiella isolates causing human urinary tract infections. J Infect Dis. 1993;168(6):1415–21.CrossRef Podschun R, Sievers D, Fischer A, Ullmann U. Serotypes, hemagglutinins, siderophore synthesis, and serum resistance of Klebsiella isolates causing human urinary tract infections. J Infect Dis. 1993;168(6):1415–21.CrossRef
18.
go back to reference Zhang R, Lin D, Chan EW, Gu D, Chen GX, Chen S. Emergence of Carbapenem-resistant serotype K1 Hypervirulent Klebsiella pneumoniae strains in China. Antimicrob Agents Chemother. 2016;60(1):709–11.CrossRef Zhang R, Lin D, Chan EW, Gu D, Chen GX, Chen S. Emergence of Carbapenem-resistant serotype K1 Hypervirulent Klebsiella pneumoniae strains in China. Antimicrob Agents Chemother. 2016;60(1):709–11.CrossRef
19.
go back to reference Russo TA, Olson R, MacDonald U, Beanan J, Davidson BA. Aerobactin, but not yersiniabactin, salmochelin, or enterobactin, enables the growth/survival of hypervirulent (hypermucoviscous) Klebsiella pneumoniae ex vivo and in vivo. Infect Immun. 2015;83(8):3325–33.CrossRef Russo TA, Olson R, MacDonald U, Beanan J, Davidson BA. Aerobactin, but not yersiniabactin, salmochelin, or enterobactin, enables the growth/survival of hypervirulent (hypermucoviscous) Klebsiella pneumoniae ex vivo and in vivo. Infect Immun. 2015;83(8):3325–33.CrossRef
20.
go back to reference Wang X, Xie Y, Li G, Liu J, Li X, Tian L, Sun J, Ou HY, Qu H. Whole-genome-sequencing characterization of bloodstream infection-causing hypervirulent Klebsiella pneumoniae of capsular serotype K2 and ST374. Virulence. 2018;9(1):510–21.CrossRef Wang X, Xie Y, Li G, Liu J, Li X, Tian L, Sun J, Ou HY, Qu H. Whole-genome-sequencing characterization of bloodstream infection-causing hypervirulent Klebsiella pneumoniae of capsular serotype K2 and ST374. Virulence. 2018;9(1):510–21.CrossRef
21.
go back to reference Liao CH, Huang YT, Chang CY, Hsu HS, Hsueh PR. Capsular serotypes and multilocus sequence types of bacteremic Klebsiella pneumoniae isolates associated with different types of infections. Eur J Clin Microbiol Infect Dis. 2014;33(3):365–9.CrossRef Liao CH, Huang YT, Chang CY, Hsu HS, Hsueh PR. Capsular serotypes and multilocus sequence types of bacteremic Klebsiella pneumoniae isolates associated with different types of infections. Eur J Clin Microbiol Infect Dis. 2014;33(3):365–9.CrossRef
22.
go back to reference Yan Q, Zhou M, Zou M, Liu WE. Hypervirulent Klebsiella pneumoniae induced ventilator-associated pneumonia in mechanically ventilated patients in China. Eur J Clin Microbiol Infect Dis. 2016;35(3):387–96.CrossRef Yan Q, Zhou M, Zou M, Liu WE. Hypervirulent Klebsiella pneumoniae induced ventilator-associated pneumonia in mechanically ventilated patients in China. Eur J Clin Microbiol Infect Dis. 2016;35(3):387–96.CrossRef
23.
go back to reference Yu WL, Ko WC, Cheng KC, Lee CC, Lai CC, Chuang YC. Comparison of prevalence of virulence factors for Klebsiella pneumoniae liver abscesses between isolates with capsular K1/K2 and non-K1/K2 serotypes. Diagn Microbiol Infect Dis. 2008;62(1):1–6.CrossRef Yu WL, Ko WC, Cheng KC, Lee CC, Lai CC, Chuang YC. Comparison of prevalence of virulence factors for Klebsiella pneumoniae liver abscesses between isolates with capsular K1/K2 and non-K1/K2 serotypes. Diagn Microbiol Infect Dis. 2008;62(1):1–6.CrossRef
24.
go back to reference Vuotto C, Longo F, Balice MP, Donelli G, Varaldo PE. Antibiotic Resistance Related to Biofilm Formation in Klebsiella pneumoniae. Pathogens (Basel, Switzerland). 2014;3(3):743–58. Vuotto C, Longo F, Balice MP, Donelli G, Varaldo PE. Antibiotic Resistance Related to Biofilm Formation in Klebsiella pneumoniae. Pathogens (Basel, Switzerland). 2014;3(3):743–58.
25.
go back to reference Stahlhut SG, Chattopadhyay S, Kisiela DI, Hvidtfeldt K, Clegg S, Struve C, Sokurenko EV, Krogfelt KA. Structural and population characterization of MrkD, the adhesive subunit of type 3 fimbriae. J Bacteriol. 2013;195(24):5602–13.CrossRef Stahlhut SG, Chattopadhyay S, Kisiela DI, Hvidtfeldt K, Clegg S, Struve C, Sokurenko EV, Krogfelt KA. Structural and population characterization of MrkD, the adhesive subunit of type 3 fimbriae. J Bacteriol. 2013;195(24):5602–13.CrossRef
26.
go back to reference Mei YF, Liu PP, Wan LG, Liu Y, Wang LH, Wei DD, Deng Q, Cao XW. Virulence and genomic feature of a virulent Klebsiella pneumoniae sequence type 14 strain of serotype K2 harboring blaNDM-5 in China. Front Microbiol. 2017;8:335.PubMedPubMedCentral Mei YF, Liu PP, Wan LG, Liu Y, Wang LH, Wei DD, Deng Q, Cao XW. Virulence and genomic feature of a virulent Klebsiella pneumoniae sequence type 14 strain of serotype K2 harboring blaNDM-5 in China. Front Microbiol. 2017;8:335.PubMedPubMedCentral
27.
go back to reference Chiang TT, Yang YS, Yeh KM, Chiu SK, Wang NC, Lin TY, Huang LY, Chang FY, Siu LK, Lin JC, et al. Quantification and comparison of virulence and characteristics of different variants of carbapenemase-producing Klebsiella pneumoniae clinical isolates from Taiwan and the United States. J Microbiol Immunol Infection. 2016;49(1):83–90.CrossRef Chiang TT, Yang YS, Yeh KM, Chiu SK, Wang NC, Lin TY, Huang LY, Chang FY, Siu LK, Lin JC, et al. Quantification and comparison of virulence and characteristics of different variants of carbapenemase-producing Klebsiella pneumoniae clinical isolates from Taiwan and the United States. J Microbiol Immunol Infection. 2016;49(1):83–90.CrossRef
28.
go back to reference Hennequin C, Robin F. Correlation between antimicrobial resistance and virulence in Klebsiella pneumoniae. Eur J Clin Microbiol Infect Dis. 2016;35(3):333–41.CrossRef Hennequin C, Robin F. Correlation between antimicrobial resistance and virulence in Klebsiella pneumoniae. Eur J Clin Microbiol Infect Dis. 2016;35(3):333–41.CrossRef
29.
go back to reference Gottig S, Riedel-Christ S, Saleh A, Kempf VA, Hamprecht A. Impact of blaNDM-1 on fitness and pathogenicity of Escherichia coli and Klebsiella pneumoniae. Int J Antimicrob Agents. 2016;47(6):430–5.CrossRef Gottig S, Riedel-Christ S, Saleh A, Kempf VA, Hamprecht A. Impact of blaNDM-1 on fitness and pathogenicity of Escherichia coli and Klebsiella pneumoniae. Int J Antimicrob Agents. 2016;47(6):430–5.CrossRef
30.
go back to reference Chen L, Mathema B, Chavda KD, DeLeo FR, Bonomo RA, Kreiswirth BN. Carbapenemase-producing Klebsiella pneumoniae: molecular and genetic decoding. Trends Microbiol. 2014;22(12):686–96.CrossRef Chen L, Mathema B, Chavda KD, DeLeo FR, Bonomo RA, Kreiswirth BN. Carbapenemase-producing Klebsiella pneumoniae: molecular and genetic decoding. Trends Microbiol. 2014;22(12):686–96.CrossRef
31.
go back to reference Siu LK, Huang DB, Chiang T. Plasmid transferability of KPC into a virulent K2 serotype Klebsiella pneumoniae. BMC Infect Dis. 2014;14:176.CrossRef Siu LK, Huang DB, Chiang T. Plasmid transferability of KPC into a virulent K2 serotype Klebsiella pneumoniae. BMC Infect Dis. 2014;14:176.CrossRef
32.
go back to reference Zhang Y, Zhao C, Wang Q, Wang X, Chen H, Li H, Zhang F, Li S, Wang R, Wang H. High prevalence of Hypervirulent Klebsiella pneumoniae infection in China: geographic distribution, clinical characteristics, and antimicrobial resistance. Antimicrob Agents Chemother. 2016;60(10):6115–20.CrossRef Zhang Y, Zhao C, Wang Q, Wang X, Chen H, Li H, Zhang F, Li S, Wang R, Wang H. High prevalence of Hypervirulent Klebsiella pneumoniae infection in China: geographic distribution, clinical characteristics, and antimicrobial resistance. Antimicrob Agents Chemother. 2016;60(10):6115–20.CrossRef
Metadata
Title
Outbreak of KPC-2 Carbapenem-resistant Klebsiella pneumoniae ST76 and Carbapenem-resistant K2 Hypervirulent Klebsiella pneumoniae ST375 strains in Northeast China: molecular and virulent characteristics
Authors
Shanshan Su
Jisheng Zhang
Yongxin Zhao
Lan Yu
Yong Wang
Yuchao Wang
Mingjia Bao
Yu Fu
Chunjiang Li
Xiaoli Zhang
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2020
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-020-05143-y

Other articles of this Issue 1/2020

BMC Infectious Diseases 1/2020 Go to the issue