Dataset Information

Clonal Dissemination of Clinical Carbapenem-Resistant Klebsiella pneumoniae Isolates Carrying fosA3 and bla _KPC-2 Coharboring Plasmids in Shandong, China.

ABSTRACT: Treatment strategies of infection by carbapenem-resistant Klebsiella pneumoniae (CRKP) are limited. Fosfomycin, a broad-spectrum antibiotic, has attracted renewed interest in combination therapy to fight K. pneumoniae infections. However, reports on fosfomycin-resistant K. pneumoniae are increasing. Among the 57 CRKP strains, 40 (70.2%) were resistant to fosfomycin. Thus, whole-genome sequencing and bioinformatics analysis were conducted to reveal molecular characteristics of fosfomycin-resistant K. pneumoniae. Twenty-three isolates coharbored fosA ^kp and fosA3, with K. pneumoniae carbapenemase (KPC)-producing ST11-KL64-wzi64-O2 (n = 13) and ST11-KL47-wzi209-OL101 (n = 8), the predominating clonal groups, while fosA3 was not detected in isolates carrying class B carbapenemase genes. Twenty-two (out of 26) ST11-KL64 strains were positive for rmpA2, of which 12 carried fosA3. Four of the 23 fosA3-positive isolates could successfully transfer their fosfomycin-resistant determinants to Escherichia coli J53Azi ^R . All four strains belonged to ST11-KL47 with the same pulsed-field gel electrophoresis profile, and their transconjugants acquired fosfomycin, carbapenem, and aminoglycoside resistance. A 127-kb conjugative pCT-KPC-like hybrid plasmid (pJNKPN52_KPC_fosA) coharboring fosA3, bla _KPC-2, bla _CTX-M-65, bla _SHV-12, rmtB, and bla _TEM-1 was identified. ST11-KL64 and ST11-KL47 K. pneumoniae, with higher resistance and virulence, should be critically monitored to prevent the future dissemination of resistance.

SUBMITTER: Hao Y

PROVIDER: S-EPMC8718808 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Clonal Dissemination of Clinical Carbapenem-Resistant Klebsiella pneumoniae Isolates Carrying fosA3 and bla KPC-2 Coharboring Plasmids in Shandong, China.

Hao Yingying Y Zhao Xuguang X Zhang Cui C Bai Yuanyuan Y Song Zhen Z Lu Xinglun X Chen Ran R Zhu Yaoyao Y Wang Yueling Y

Frontiers in microbiology 20211217

Treatment strategies of infection by carbapenem-resistant Klebsiella pneumoniae (CRKP) are limited. Fosfomycin, a broad-spectrum antibiotic, has attracted renewed interest in combination therapy to fight K. pneumoniae infections. However, reports on fosfomycin-resistant K. pneumoniae are increasing. Among the 57 CRKP strains, 40 (70.2%) were resistant to fosfomycin. Thus, whole-genome sequencing and bioinformatics analysis were conducted to reveal molecular characteristics o ...[more]

PMID: 34975798

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Project description:IntroductionColistin is regarded as one of the last-resort antibiotics against severe infections caused by carbapenem-resistant Enterobacteriaceae. Strains with cooccurrence of mcr-9 and carbapenemase genes are of particular concern. This study aimed to investigate the genetic characteristics of a bla KPC-2-carrying plasmid, bla NDM-1-carrying plasmid and mcr-9-carrying plasmid coexisting in a carbapenem-resistant Enterobacter hormaechei isolate.MethodsE. hormaechei strain E1532 was subjected to whole-genome sequencing, and the complete nucleotide sequences of three resistance plasmids identified in the strain were compared with related plasmid sequences. The resistance phenotypes mediated by these plasmids were analyzed by plasmid transfer, carbapenemase activity and antimicrobial susceptibility testing.ResultsWhole-genome sequencing revealed that strain E1532 carries three different resistance plasmids, pE1532-KPC, pE1532-NDM and pE1532-MCR. pE1532-KPC harboring bla KPC-2 and pE1532-NDM harboring bla NDM-1 are highly identical to the IncR plasmid pHN84KPC and IncX3 plasmid pNDM-HN380, respectively. The mcr-9-carrying plasmid pE1532-MCR possesses a backbone highly similar to that of the IncHI2 plasmids R478 and p505108-MDR, though their accessory modules differ. These three coexisting plasmids carry a large number of resistance genes and contribute to high resistance to almost all antibiotics tested, except for amikacin, trimethoprim/sulfamethoxazole, tigecycline and polymyxin B. Most of the plasmid-mediated resistance genes are located in or flanked by various mobile genetic elements, facilitating horizontal transfer of antibiotic resistance genes.DiscussionThis is the first report of a single E. hormaechei isolate with coexistence of three resistance plasmids carrying mcr-9 and the two most common carbapenemase genes, bla KPC-2 and bla NDM-1. The prevalence and genetic features of these coexisting plasmids should be monitored to facilitate the establishment of effective strategies to control their further spread.

Project description:Untreated wastewater is a reservoir for multidrug-resistant bacteria, but its role in the spread of antibiotic resistance in the human population remains poorly investigated. In this study, we isolated a KPC-2-producing ST2787 Klebsiella quasipneumoniae subsp. quasipneumoniae (WW14A), recovered from raw sewage at a wastewater treatment plant in Argentina in 2018 and determined its complete genome sequence. Strain WW14A was resistant to all β-lactams, ciprofloxacin and amikacin. A core genome phylogenetic analysis indicated that WW14A was closely related to a GES-5-producing Taiwanese strain isolated from hospital wastewater in 2015 and it was clearly distinct from strains isolated recently in Argentina and Brazil. Interestingly, bla KPC-2 was harbored by a recently described IncP-6 broad-spectrum plasmid which was sporadically reported worldwide and had never been reported before in Argentina. We investigated the presence of the IncP-6 replicon in isolates obtained from the same sampling and found a novel non-typable/IncP-6 hybrid plasmid in a newly assigned ST1407 Enterobacter asburiae (WW19C) also harboring bla KPC-2. Nanopore sequencing and hybrid assembly of strains WW14A and WW19C revealed that both IncP-6 plasmids shared 72% of coverage (~20 kb), with 99.99% of sequence similarity and each one also presented uniquely combined regions that were derived from other plasmids recently reported in different countries of South America, Asia, and Europe. The region harboring the carbapenem resistance gene (~11 kb) in both plasmids contained a Tn3 transposon disrupted by a Tn3-ISApu-flanked element and the core sequence was composed by ΔISKpn6/bla KPC-2/Δbla TEM-1/ISKpn27. Both strains also carried genes conferring resistance to heavy metals (e.g., arsenic, mercury, lead, cadmium, copper), pesticides (e.g., glyphosate), disinfectants, and several virulence-related genes, posing a potential pathogenic risk in the case of infections. This is the first study documenting bla KPC-2 associated with IncP-6 plasmids in K. quasipneumoniae and Enterobacter cloacae complex from wastewater in Argentina and highlights the circulation of IncP-6 plasmids as potential reservoirs of bla KPC-2 in the environment.

Dataset Information

Clonal Dissemination of Clinical Carbapenem-Resistant Klebsiella pneumoniae Isolates Carrying fosA3 and bla _KPC-2 Coharboring Plasmids in Shandong, China.

Publications

Clonal Dissemination of Clinical Carbapenem-Resistant <i>Klebsiella pneumoniae</i> Isolates Carrying <i>fosA3</i> and <i>bla</i> <sub><i>KPC</i>-2</sub> Coharboring Plasmids in Shandong, China.

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