Genetic Characterization of Enterobacter hormaechei Co-Harboring blaNDM-1 and mcr-9 Causing Upper Respiratory Tract Infection

Purpose With the spread of multiple drug-resistant bacteria, blaNDM-1 and mcr-9 have been detected in various bacteria worldwide. However, the simultaneous detection of blaNDM-1 and mcr-9 in Enterobacter hormaechei has been rarely reported. This study identified an E. hormaechei strain carrying both blaNDM-1 and mcr-9. We investigated the genetic characteristics of these two resistance genes in detail, elucidating various potential mechanisms by which they may be transmitted. Methods Bacterial genomic features and possible origins were assessed by whole-genome sequencing (WGS) with Illumina and PacBio platforms and phylogenetic analysis. Subsequent investigations were performed, including antimicrobial susceptibility testing and multilocus sequence typing (MLST). Results We isolated an E. hormaechei strain DY1901 carrying both blaNDM-1 and mcr-9 from the sputum sample. Susceptibility testing showed that the isolate was multidrug-resistant. Multiple antibiotic resistance genes and virulence genes are widely distributed in DY1901. S1-PFGE, Southern blotting, and plasmid replicon typing showed that DY1901 carried four plasmids. The plasmid carrying mcr-9 was 259Kb in size and belonged to IncHI2, while the plasmid carrying blaNDM-1 was 45Kb in length and belonged to IncX3. Conclusion The E. hormaechei strain isolated in this study has a broad antibiotic resistance spectrum, posing a challenge to clinical treatment. Plasmids carrying mcr-9 are fusion plasmids, and those taking NDM are widely disseminated in China, suggesting that we should conduct routine genomic surveillance on such plasmids to curb the spread of drug-resistant bacteria in the region.

[1]  Zhiqiang Wang,et al.  Coexistence of tet(X4), mcr-1, and blaNDM-5 in ST6775 Escherichia coli Isolates of Animal Origin in China , 2022, Microbiology spectrum.

[2]  S. Brady,et al.  A naturally inspired antibiotic to target multidrug-resistant pathogens , 2022, Nature.

[3]  Jianhua Guo,et al.  Colonization of gut microbiota by plasmid-carrying bacteria is facilitated by evolutionary adaptation to antibiotic treatment , 2021, The ISME Journal.

[4]  Liangxing Wang,et al.  First Report of Coexistence of blaSFO–1 and blaNDM–1 β-Lactamase Genes as Well as Colistin Resistance Gene mcr-9 in a Transferrable Plasmid of a Clinical Isolate of Enterobacter hormaechei , 2021, Frontiers in Microbiology.

[5]  Long Sun,et al.  Coexistence of mcr-9 and blaNDM-1 in a multidrug-resistant Enterobacter hormaechei strain recovered from a bloodstream infection in China. , 2021, Journal of global antimicrobial resistance.

[6]  Y. Chu,et al.  Carbapenem-resistant Enterobacter cloacae complex in a tertiary Hospital in Northeast China, 2010–2019 , 2021, BMC Infectious Diseases.

[7]  Junxing Yang,et al.  Enterobacter cloacae infection of the shoulder in a 52-year-old woman without apparent predisposing risk factor: a case report and literature review , 2021, BMC Infectious Diseases.

[8]  J. Hrabák,et al.  Detection of Five mcr-9-Carrying Enterobacterales Isolates in Four Czech Hospitals , 2020, mSphere.

[9]  M. A. De la Cruz,et al.  Two Type VI Secretion Systems of Enterobacter cloacae Are Required for Bacterial Competition, Cell Adherence, and Intestinal Colonization , 2020, Frontiers in Microbiology.

[10]  A. Okoh,et al.  Antibiogram Signatures of Some Enterobacteria Recovered from Irrigation Water and Agricultural Soil in two District Municipalities of South Africa , 2020, Microorganisms.

[11]  Junyoung Kim,et al.  Horizontal transfer of blaNDM-1-carrying IncX3 plasmid between carbapenem-resistant Enterobacteriaceae in a single patient. , 2020, The Journal of infection.

[12]  F. Hu,et al.  Dissemination of Carbapenemases (KPC, NDM, OXA-48, IMP, and VIM) Among Carbapenem-Resistant Enterobacteriaceae Isolated From Adult and Children Patients in China , 2020, Frontiers in Cellular and Infection Microbiology.

[13]  J. Osei Sekyere,et al.  Emergence of mcr-9.1 in Extended-Spectrum-β-Lactamase-Producing Clinical Enterobacteriaceae in Pretoria, South Africa: Global Evolutionary Phylogenomics, Resistome, and Mobilome , 2020, mSystems.

[14]  Luhua Zhang,et al.  Characterization of the global distribution and diversified plasmid reservoirs of the colistin resistance gene mcr-9 , 2020, Scientific Reports.

[15]  Guo-Bao Tian,et al.  Co-Occurrence of mcr-9 and blaNDM-1 in Enterobacter cloacae Isolated from a Patient with Bloodstream Infection , 2020, Infection and drug resistance.

[16]  Eric R. Geertsma,et al.  AcrB: a mean, keen, drug efflux machine , 2020, Annals of the New York Academy of Sciences.

[17]  Eirini Christaki,et al.  Antimicrobial Resistance in Bacteria: Mechanisms, Evolution, and Persistence , 2019, Journal of Molecular Evolution.

[18]  J. Pagés,et al.  Enterobacter spp.: Update on Taxonomy, Clinical Aspects, and Emerging Antimicrobial Resistance , 2019, Clinical Microbiology Reviews.

[19]  T. Salminen,et al.  Klebsiella pneumoniae type VI secretion system-mediated microbial competition is PhoPQ controlled and reactive oxygen species dependent , 2019, bioRxiv.

[20]  Y. Carmeli,et al.  Combining VITEK® 2 with colistin agar dilution screening assist timely reporting of colistin susceptibility. , 2019, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[21]  M. Wiedmann,et al.  Identification of Novel Mobilized Colistin Resistance Gene mcr-9 in a Multidrug-Resistant, Colistin-Susceptible Salmonella enterica Serotype Typhimurium Isolate , 2019, mBio.

[22]  H. Balkhy,et al.  Insertion element mediated mgrB disruption and presence of ISKpn28 in colistin-resistant Klebsiella pneumoniae isolates from Saudi Arabia , 2018, Infection and drug resistance.

[23]  Yang Wang,et al.  Emergence of a novel mobile colistin resistance gene, mcr-8, in NDM-producing Klebsiella pneumoniae , 2018, Emerging Microbes & Infections.

[24]  Youjun Feng,et al.  First detection and genomics analysis of KPC-2-producing Citrobacter isolates from river sediments. , 2018, Environmental pollution.

[25]  E. Svetoch,et al.  Identification of IS1R and IS10R elements inserted into ompk36 porin gene of two multidrug-resistant Klebsiella pneumoniae hospital strains. , 2017, FEMS microbiology letters.

[26]  M. A. Maciel,et al.  Clonal spread and accumulation of &bgr;‐lactam resistance determinants in Enterobacter aerogenes and Enterobacter cloacae complex isolates from infection and colonization in patients at a public hospital in Recife, Pernambuco, Brazil , 2017, Journal of medical microbiology.

[27]  Yonghong Xiao,et al.  Coexistence of MCR-1 and NDM-1 in Clinical Escherichia coli Isolates. , 2016, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[28]  Jianzhong Shen,et al.  Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. , 2015, The Lancet. Infectious diseases.

[29]  Yonghong Xiao,et al.  Emergence of Raoultella ornithinolytica Coproducing IMP-4 and KPC-2 Carbapenemases in China , 2015, Antimicrobial Agents and Chemotherapy.

[30]  Jacqueline A. Keane,et al.  Rapid phylogenetic analysis of large samples of recombinant bacterial whole genome sequences using Gubbins , 2014, Nucleic acids research.

[31]  G. Dalmasso,et al.  IS1R-Mediated Plasticity of IncL/M Plasmids Leads to the Insertion of blaOXA-48 into the Escherichia coli Chromosome , 2014, Antimicrobial Agents and Chemotherapy.

[32]  Hui Wang,et al.  Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases. , 2013, The Lancet. Infectious diseases.

[33]  S. Stefani,et al.  Enterobacter cloacae complex: clinical impact and emerging antibiotic resistance. , 2012, Future microbiology.

[34]  D. Livermore,et al.  The emerging NDM carbapenemases. , 2011, Trends in microbiology.

[35]  J. Turnidge,et al.  Colistin: the re-emerging antibiotic for multidrug-resistant Gram-negative bacterial infections. , 2006, The Lancet. Infectious diseases.

[36]  C. Sanders,et al.  Enterobacter spp.: pathogens poised to flourish at the turn of the century , 1997, Clinical microbiology reviews.