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Published in: BMC Infectious Diseases 1/2020

01-12-2020 | Imipenem | Research article

Emergence of carbapenem-resistant and colistin-susceptible Enterobacter cloacae complex co-harboring blaIMP-1 and mcr-9 in Japan

Authors: Pegah Kananizadeh, Satoshi Oshiro, Shin Watanabe, Shu Iwata, Kyoko Kuwahara-Arai, Masahiro Shimojima, Miho Ogawa, Tatsuya Tada, Teruo Kirikae

Published in: BMC Infectious Diseases | Issue 1/2020

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Abstract

Background

The spread of Enterobacteriaceae producing both carbapenemases and Mcr, encoded by plasmid-mediated colistin resistance genes, has become a serious public health problem worldwide. This study describes three clinical isolates of Enterobacter cloacae complex co-harboring blaIMP-1 and mcr-9 that were resistant to carbapenem but susceptible to colistin.

Methods

Thirty-two clinical isolates of E. cloacae complex non-susceptible to carbapenems were obtained from patients at 14 hospitals in Japan. Their minimum inhibitory concentrations (MICs) were determined by broth microdilution methods and E-tests. Their entire genomes were sequenced by MiSeq and MinION methods. Multilocus sequence types were determined and a phylogenetic tree constructed by single nucleotide polymorphism (SNP) alignment of whole genome sequencing data.

Results

All 32 isolates showed MICs of ≥2 μg/ml for imipenem and/or meropenem. Whole-genome analysis revealed that all these isolates harbored blaIMP-1, with three also harboring mcr-9. These three isolates showed low MICs of 0.125 μg/ml for colistin. In two of these isolates, blaIMP-1 and mcr-9 were present on two separate plasmids, of sizes 62 kb and 280/290 kb, respectively. These two isolates did not possess a qseBC gene encoding a two-component system, which is thought to regulate the expression of mcr-9. In the third isolate, however, both blaIMP-1 and mcr-9 were present on the chromosome.

Conclusion

The mcr-9 is silently distributed among carbapenem-resistant E. cloacae complex isolates, of which are emerging in hospitals in Japan. To our knowledge, this is the first report of isolates of E. cloacae complex harboring both blaIMP-1 and mcr-9 in Japan.
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Literature
1.
go back to reference Nordmann P, Poirel L. The difficult-to-control spread of carbapenemase producers among Enterobacteriaceae worldwide. Clin Microbiol Infect. 2014;20(9):821–30.CrossRef Nordmann P, Poirel L. The difficult-to-control spread of carbapenemase producers among Enterobacteriaceae worldwide. Clin Microbiol Infect. 2014;20(9):821–30.CrossRef
2.
go back to reference Cornaglia G, Giamarellou H, Rossolini GM. Metallo-beta-lactamases: a last frontier for beta-lactams? Lancet Infect Dis. 2011;11(5):381–93.CrossRef Cornaglia G, Giamarellou H, Rossolini GM. Metallo-beta-lactamases: a last frontier for beta-lactams? Lancet Infect Dis. 2011;11(5):381–93.CrossRef
3.
go back to reference Jeannot K, Bolard A, Plesiat P. Resistance to polymyxins in gram-negative organisms. Int J Antimicrob Agents. 2017;49(5):526–35.CrossRef Jeannot K, Bolard A, Plesiat P. Resistance to polymyxins in gram-negative organisms. Int J Antimicrob Agents. 2017;49(5):526–35.CrossRef
4.
go back to reference Falagas ME, Kasiakou SK. Colistin: the revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections. Clin Infect Dis. 2005;40(9):1333–41.CrossRef Falagas ME, Kasiakou SK. Colistin: the revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections. Clin Infect Dis. 2005;40(9):1333–41.CrossRef
5.
go back to reference Olaitan AO, Morand S, Rolain JM. Mechanisms of polymyxin resistance: acquired and intrinsic resistance in bacteria. Front Microbiol. 2014;5:643.CrossRef Olaitan AO, Morand S, Rolain JM. Mechanisms of polymyxin resistance: acquired and intrinsic resistance in bacteria. Front Microbiol. 2014;5:643.CrossRef
6.
go back to reference Osei SJ. Mcr colistin resistance gene: a systematic review of current diagnostics and detection methods. Microbiologyopen. 2019;8(4):e00682.CrossRef Osei SJ. Mcr colistin resistance gene: a systematic review of current diagnostics and detection methods. Microbiologyopen. 2019;8(4):e00682.CrossRef
7.
go back to reference Esposito F, Fernandes MR, Lopes R, Munoz M, Sabino CP, Cunha MP, et al. Detection of colistin-resistant MCR-1-positive Escherichia coli by use of assays based on inhibition by EDTA and zeta potential. J Clin Microbiol. 2017;55(12):3454–65.CrossRef Esposito F, Fernandes MR, Lopes R, Munoz M, Sabino CP, Cunha MP, et al. Detection of colistin-resistant MCR-1-positive Escherichia coli by use of assays based on inhibition by EDTA and zeta potential. J Clin Microbiol. 2017;55(12):3454–65.CrossRef
8.
go back to reference Abdul Momin MHF, Bean DC, Hendriksen RS, Haenni M, Phee LM, Wareham DW. CHROMagar COL-APSE: a selective bacterial culture medium for the isolation and differentiation of colistin-resistant gram-negative pathogens. J Med Microbiol. 2017;66(11):1554–61.CrossRef Abdul Momin MHF, Bean DC, Hendriksen RS, Haenni M, Phee LM, Wareham DW. CHROMagar COL-APSE: a selective bacterial culture medium for the isolation and differentiation of colistin-resistant gram-negative pathogens. J Med Microbiol. 2017;66(11):1554–61.CrossRef
9.
go back to reference Liu YY, Wang Y, Walsh TR, Yi LX, Zhang R, Spencer J, et al. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis. 2016;16(2):161–8.CrossRef Liu YY, Wang Y, Walsh TR, Yi LX, Zhang R, Spencer J, et al. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis. 2016;16(2):161–8.CrossRef
10.
go back to reference Carroll LM, Gaballa A, Guldimann C, Sullivan G, Henderson LO, Wiedmann M. Identification of novel mobilized colistin resistance gene mcr-9 in a multidrug-resistant, colistin-susceptible Salmonella enterica serotype Typhimurium isolate. mBio. 2019;10(3). Carroll LM, Gaballa A, Guldimann C, Sullivan G, Henderson LO, Wiedmann M. Identification of novel mobilized colistin resistance gene mcr-9 in a multidrug-resistant, colistin-susceptible Salmonella enterica serotype Typhimurium isolate. mBio. 2019;10(3).
11.
go back to reference Yuan Y, Li Y, Wang G, Li C, Xiang L, She J, et al. Coproduction of MCR-9 and NDM-1 by colistin-resistant Enterobacter hormaechei isolated from bloodstream infection. Infect Drug Resist. 2019;12:2979–85.CrossRef Yuan Y, Li Y, Wang G, Li C, Xiang L, She J, et al. Coproduction of MCR-9 and NDM-1 by colistin-resistant Enterobacter hormaechei isolated from bloodstream infection. Infect Drug Resist. 2019;12:2979–85.CrossRef
12.
go back to reference Huang L, Wang X, Feng Y, Xie Y, Xie L, Zong Z. First identification of an IMI-1 carbapenemase-producing colistin-resistant Enterobacter cloacae in China. Ann Clin Microbiol Antimicrob. 2015;14:51.CrossRef Huang L, Wang X, Feng Y, Xie Y, Xie L, Zong Z. First identification of an IMI-1 carbapenemase-producing colistin-resistant Enterobacter cloacae in China. Ann Clin Microbiol Antimicrob. 2015;14:51.CrossRef
13.
go back to reference Miltgen G, Bonnin RA, Avril C, Benoit-Cattin T, Martak D, Leclaire A, et al. Outbreak of IMI-1 carbapenemase-producing colistin-resistant Enterobacter cloacae on the French island of Mayotte (Indian Ocean). Int J Antimicrob Agents. 2018;52(3):416–20.CrossRef Miltgen G, Bonnin RA, Avril C, Benoit-Cattin T, Martak D, Leclaire A, et al. Outbreak of IMI-1 carbapenemase-producing colistin-resistant Enterobacter cloacae on the French island of Mayotte (Indian Ocean). Int J Antimicrob Agents. 2018;52(3):416–20.CrossRef
14.
go back to reference Manohar P, Shanthini T, Ayyanar R, Bozdogan B, Wilson A, Tamhankar AJ, et al. The distribution of carbapenem- and colistin-resistance in gram-negative bacteria from the Tamil Nadu region in India. J Med Microbiol. 2017;66(7):874–83.CrossRef Manohar P, Shanthini T, Ayyanar R, Bozdogan B, Wilson A, Tamhankar AJ, et al. The distribution of carbapenem- and colistin-resistance in gram-negative bacteria from the Tamil Nadu region in India. J Med Microbiol. 2017;66(7):874–83.CrossRef
15.
go back to reference Norgan AP, Freese JM, Tuin PM, Cunningham SA, Jeraldo PR, Patel R. Carbapenem- and colistin-resistant Enterobacter cloacae from Delta, Colorado, in 2015. Antimicrob Agents Chemother. 2016;60(5):3141–4.CrossRef Norgan AP, Freese JM, Tuin PM, Cunningham SA, Jeraldo PR, Patel R. Carbapenem- and colistin-resistant Enterobacter cloacae from Delta, Colorado, in 2015. Antimicrob Agents Chemother. 2016;60(5):3141–4.CrossRef
16.
go back to reference Chavda KD, Westblade LF, Satlin MJ, Hemmert AC, Castanheira M, Jenkins SG, et al. First report of bla VIM-4- and mcr-9-coharboring Enterobacter species isolated from a pediatric patient. mSphere. 2019;4:5.CrossRef Chavda KD, Westblade LF, Satlin MJ, Hemmert AC, Castanheira M, Jenkins SG, et al. First report of bla VIM-4- and mcr-9-coharboring Enterobacter species isolated from a pediatric patient. mSphere. 2019;4:5.CrossRef
17.
go back to reference Le-Ha TD, Le L, Le-Vo HN, Anda M, Motooka D, Nakamura S, et al. Characterization of a carbapenem- and colistin-resistant Enterobacter cloacae carrying Tn6901 in Bla NDM-1 genomic context. Infect Drug Resist. 2019;12:733–9.CrossRef Le-Ha TD, Le L, Le-Vo HN, Anda M, Motooka D, Nakamura S, et al. Characterization of a carbapenem- and colistin-resistant Enterobacter cloacae carrying Tn6901 in Bla NDM-1 genomic context. Infect Drug Resist. 2019;12:733–9.CrossRef
18.
go back to reference Srinivas P, Rivard K. Polymyxin resistance in gram-negative pathogens. Curr Infect Dis Rep. 2017;19(11):38.CrossRef Srinivas P, Rivard K. Polymyxin resistance in gram-negative pathogens. Curr Infect Dis Rep. 2017;19(11):38.CrossRef
19.
go back to reference Tumbarello M, Trecarichi EM, De Rosa FG, Giannella M, Giacobbe DR, Bassetti M, et al. Infections caused by KPC-producing Klebsiella pneumoniae: differences in therapy and mortality in a multicentre study. J Antimicrob Chemother. 2015;70(7):2133–43.CrossRef Tumbarello M, Trecarichi EM, De Rosa FG, Giannella M, Giacobbe DR, Bassetti M, et al. Infections caused by KPC-producing Klebsiella pneumoniae: differences in therapy and mortality in a multicentre study. J Antimicrob Chemother. 2015;70(7):2133–43.CrossRef
20.
go back to reference CLSI. In: Clinical and Laboratory Standards Institute, editor. Performance Standards for Antimicrobial Susceptibility Testing. 29th. CLSI supplement M100. Wayne, PA; 2019. CLSI. In: Clinical and Laboratory Standards Institute, editor. Performance Standards for Antimicrobial Susceptibility Testing. 29th. CLSI supplement M100. Wayne, PA; 2019.
22.
go back to reference Yoon SH, Ha SM, Lim J, Kwon S, Chun J. A large-scale evaluation of algorithms to calculate average nucleotide identity. Antonie Van Leeuwenhoek. 2017;110(10):1281–6.CrossRef Yoon SH, Ha SM, Lim J, Kwon S, Chun J. A large-scale evaluation of algorithms to calculate average nucleotide identity. Antonie Van Leeuwenhoek. 2017;110(10):1281–6.CrossRef
23.
go back to reference Meier-Kolthoff JP, Auch AF, Klenk HP, Goker M. Genome sequence-based species delimitation with confidence intervals and improved distance functions. BMC Bioinformatics. 2013;14:60.CrossRef Meier-Kolthoff JP, Auch AF, Klenk HP, Goker M. Genome sequence-based species delimitation with confidence intervals and improved distance functions. BMC Bioinformatics. 2013;14:60.CrossRef
24.
go back to reference Kieffer N, Royer G, Decousser JW, Bourrel AS, Palmieri M, Ortiz De La Rosa JM, et al. mcr-9, an inducible gene encoding an acquired phosphoethanolamine transferase in Escherichia coli, and its origin. Antimicrob Agents Chemother. 2019;63:9. Kieffer N, Royer G, Decousser JW, Bourrel AS, Palmieri M, Ortiz De La Rosa JM, et al. mcr-9, an inducible gene encoding an acquired phosphoethanolamine transferase in Escherichia coli, and its origin. Antimicrob Agents Chemother. 2019;63:9.
25.
go back to reference Andersen PS, Stegger M, Aziz M, Contente-Cuomo T, Gibbons HS, Keim P, et al. Complete genome sequence of the epidemic and highly virulent CTX-M-15-producing H30-Rx subclone of Escherichia coli ST131. Genome Announc. 2013;1:6.CrossRef Andersen PS, Stegger M, Aziz M, Contente-Cuomo T, Gibbons HS, Keim P, et al. Complete genome sequence of the epidemic and highly virulent CTX-M-15-producing H30-Rx subclone of Escherichia coli ST131. Genome Announc. 2013;1:6.CrossRef
26.
go back to reference Clarke MB, Sperandio V. Transcriptional autoregulation by quorum sensing Escherichia coli regulators B and C (QseBC) in enterohaemorrhagic E. coli (EHEC). Mol Microbiol. 2005;58(2):441–55.CrossRef Clarke MB, Sperandio V. Transcriptional autoregulation by quorum sensing Escherichia coli regulators B and C (QseBC) in enterohaemorrhagic E. coli (EHEC). Mol Microbiol. 2005;58(2):441–55.CrossRef
27.
go back to reference Falgenhauer L, Waezsada S-E, Gwozdzinski K, Ghosh H, Doijad S, Bunk B, et al. Chromosomal locations of mcr-1 and blaCTX-M-15 in fluoroquinolone-resistant Escherichia coli ST410. Emerg Infect Dis. 2016;22(9):1689.CrossRef Falgenhauer L, Waezsada S-E, Gwozdzinski K, Ghosh H, Doijad S, Bunk B, et al. Chromosomal locations of mcr-1 and blaCTX-M-15 in fluoroquinolone-resistant Escherichia coli ST410. Emerg Infect Dis. 2016;22(9):1689.CrossRef
28.
go back to reference Sun J, Li XP, Fang LX, Sun RY, He YZ, Lin J, et al. Co-occurrence of mcr-1 in the chromosome and on an IncHI2 plasmid: persistence of colistin resistance in Escherichia coli. Int J Antimicrob Agents. 2018;51(6):842–7.CrossRef Sun J, Li XP, Fang LX, Sun RY, He YZ, Lin J, et al. Co-occurrence of mcr-1 in the chromosome and on an IncHI2 plasmid: persistence of colistin resistance in Escherichia coli. Int J Antimicrob Agents. 2018;51(6):842–7.CrossRef
29.
go back to reference Yu H, Qu F, Shan B, Huang B, Jia W, Chen C, et al. Detection of the mcr-1 colistin resistance gene in carbapenem-resistant Enterobacteriaceae from different hospitals in China. Antimicrob Agents Chemother. 2016;60(8):5033–5.CrossRef Yu H, Qu F, Shan B, Huang B, Jia W, Chen C, et al. Detection of the mcr-1 colistin resistance gene in carbapenem-resistant Enterobacteriaceae from different hospitals in China. Antimicrob Agents Chemother. 2016;60(8):5033–5.CrossRef
30.
go back to reference Veldman K, van Essen-Zandbergen A, Rapallini M, Wit B, Heymans R, van Pelt W, et al. Location of colistin resistance gene mcr-1 in Enterobacteriaceae from livestock and meat. J Antimicrob Chemother. 2016;71(8):2340–2.CrossRef Veldman K, van Essen-Zandbergen A, Rapallini M, Wit B, Heymans R, van Pelt W, et al. Location of colistin resistance gene mcr-1 in Enterobacteriaceae from livestock and meat. J Antimicrob Chemother. 2016;71(8):2340–2.CrossRef
31.
go back to reference AbuOun M, Stubberfield EJ, Duggett NA, Kirchner M, Dormer L, Nunez-Garcia J, et al. Mcr-1 and mcr-2 variant genes identified in Moraxella species isolated from pigs in Great Britain from 2014 to 2015. J Antimicrob Chemother. 2017;72(10):2745–9.CrossRef AbuOun M, Stubberfield EJ, Duggett NA, Kirchner M, Dormer L, Nunez-Garcia J, et al. Mcr-1 and mcr-2 variant genes identified in Moraxella species isolated from pigs in Great Britain from 2014 to 2015. J Antimicrob Chemother. 2017;72(10):2745–9.CrossRef
32.
go back to reference Zając MM, Sztromwasser P, Bortolaia V, Leekitcharoenphon P, Cavaco LM, Ziętek-Barszcz A, et al. Occurrence and characterization of mcr-1-positive Escherichia coli isolated from food-producing animals in Poland, 2011-2016. Front Microbiol. 2019;10:1753.CrossRef Zając MM, Sztromwasser P, Bortolaia V, Leekitcharoenphon P, Cavaco LM, Ziętek-Barszcz A, et al. Occurrence and characterization of mcr-1-positive Escherichia coli isolated from food-producing animals in Poland, 2011-2016. Front Microbiol. 2019;10:1753.CrossRef
33.
go back to reference Zhou HW, Zhang T, Ma JH, Fang Y, Wang HY, Huang ZX, et al. Occurrence of plasmid- and chromosome-carried mcr-1 in waterborne Enterobacteriaceae in China. Antimicrob Agents Chemother. 2017;61:8. Zhou HW, Zhang T, Ma JH, Fang Y, Wang HY, Huang ZX, et al. Occurrence of plasmid- and chromosome-carried mcr-1 in waterborne Enterobacteriaceae in China. Antimicrob Agents Chemother. 2017;61:8.
Metadata
Title
Emergence of carbapenem-resistant and colistin-susceptible Enterobacter cloacae complex co-harboring blaIMP-1 and mcr-9 in Japan
Authors
Pegah Kananizadeh
Satoshi Oshiro
Shin Watanabe
Shu Iwata
Kyoko Kuwahara-Arai
Masahiro Shimojima
Miho Ogawa
Tatsuya Tada
Teruo Kirikae
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/s12879-020-05021-7

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