Infection and Drug Resistance (Nov 2019)

Coexistence Of Plasmid-Mediated mcr-1 And blaNDM-4 Genes In A Klebsiella pneumoniae Clinical Strain In Vietnam

  • Le L,
  • Tran LK,
  • Le-Ha TD,
  • Tran BP,
  • Le-Vo HN,
  • Nguyen YN,
  • Nguyen HL,
  • Hoang-Ngoc KQ,
  • Matsumoto Y,
  • Motooka D,
  • Nakamura S,
  • Jones JW,
  • Iida T,
  • Cao V

Journal volume & issue
Vol. Volume 12
pp. 3703 – 3707

Abstract

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Lien Le,1,* Linh Khanh Tran,1,* Tam-Duong Le-Ha,1 Bich-Phuong Tran,1 Hong-Ngoc Le-Vo,1 Yen-Nhi Nguyen,1 Hanh-Lan Nguyen,1 Khanh-Quynh Hoang-Ngoc,1 Yuki Matsumoto,2 Daisuke Motooka,2 Shota Nakamura,2 James W Jones,3 Tetsuya Iida,2,4 Van Cao1 1Department of Immunology and Microbiology, Pasteur Institute in Ho Chi Minh City, Ho Chi Minh City, Vietnam; 2Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; 3Department of Bacterial and Parasitic Diseases, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; 4Department of Bacterial Infections, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan*These authors contributed equally to this workCorrespondence: Van CaoDepartment of Immunology and Microbiology, Pasteur Institute in Ho Chi Minh City, 167 Pasteur Street, District 3, Ho Chi Minh City, VietnamTel +8428 38 205131Fax +8428 38 231419Email [email protected]: In this study, we characterized the first clinical Klebsiella pneumoniae strain co- harboring mcr-1 and blaNDM-4 genes in Vietnam, which was recovered from a patient admitted to hospital in 2015. This strain demonstrated nonsusceptible to all tested antibiotics, including last-line antibiotics such as carbapenems (MICs ≥128 μg/mL) and colistin (MIC =32 μg/mL), except tigecycline (MIC =1 μg/mL). Whole-genome analysis using both MinION and MiSeq data revealed that the strain carried 29 resistance genes. Particularly, mcr-1 and blaNDM-4 genes were carried by different self-conjugative plasmids and able to be transferred to a recipient by conjugation. The colistin resistance of this strain was conferred by mcr-1 and additional chromosomal resistance determinants. Eight amino acid substitutions found in PmrA, PmrB, PmrC, PmrI, and PmrJ, all proteins that are involved in lipopolysaccharide modifications, may be associated with chromosomal colistin resistance. The accumulation of multiple antibiotic resistance mechanisms in this clinical isolate raises alarm on potential spread of extensively drug-resistant K. pneumoniae in healthcare settings.Keywords: coexistence, mcr-1, blaNDM-4, Klebsiella pneumoniae, Vietnam  

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