Genomic Analysis of Carbapenemase - Producing Extensively Drug-Resistant Klebsiella pneumoniae Isolates Reveals the Horizontal Spread of p18-43_01 Plasmid Encoding blaNDM-1 in South Africa

Yogandree Ramsamy; Koleka P Mlisana; Mushal Allam; Daniel G Amoako; Akebe L K Abia; Arshad Ismail; Ravesh Singh; Theroshnie Kisten; Khine Swe Han; David J Jackson Muckart; Timothy Hardcastle; Moosa Suleman; Sabiha Y Essack

doi:10.3390/microorganisms8010137

Genomic Analysis of Carbapenemase - Producing Extensively Drug-Resistant Klebsiella pneumoniae Isolates Reveals the Horizontal Spread of p18-43_01 Plasmid Encoding bla_NDM-1 in South Africa

Microorganisms. 2020 Jan 17;8(1):137. doi: 10.3390/microorganisms8010137.

Authors

Yogandree Ramsamy^{1

2

3}, Koleka P Mlisana^{2

3}, Mushal Allam⁴, Daniel G Amoako¹, Akebe L K Abia³, Arshad Ismail⁴, Ravesh Singh^{2

3}, Theroshnie Kisten^{5

6}, Khine Swe Han^{2

3}, David J Jackson Muckart⁷, Timothy Hardcastle⁷, Moosa Suleman⁸, Sabiha Y Essack¹

Affiliations

¹ Antimicrobial Research Unit, College of Health Sciences, University of KwaZulu-Natal, Durban 4000, South Africa.
² Medical Microbiology, National Health Laboratory Services, Durban 4000, South Africa.
³ Medical Microbiology, College of Health Sciences, University of KwaZulu-Natal, Durban 4000, South Africa.
⁴ Sequencing Core Facility, National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg 2131, South Africa.
⁵ School of Clinical Medicine, Discipline of Anaesthetics & Critical Care, College of Health Sciences, University of KwaZulu-Natal, Durban 4000, South Africa.
⁶ Inkosi Albert Luthuli Central Hospital, Department of Critical Care, College of Health Sciences, University of KwaZulu-Natal, Durban 4000, South Africa.
⁷ Inkosi Albert Luthuli Central Hospital, Department of Surgery & Trauma Unit, College of Health Sciences, University of KwaZulu-Natal, Durban 4000, South Africa.
⁸ Ahmed Al-Kadi Private Hospital, Durban 4000, South Africa.

Abstract

Whole-genome sequence (WGS) analyses were employed to investigate the genomic epidemiology of extensively drug-resistant Klebsiella pneumoniae strains, focusing on the carbapenem resistance-encoding determinants, mobile genetic support, clonal and epidemiological relationships. A total of ten isolates were obtained from patients admitted to the intensive care unit (ICU) in a public hospital in South Africa. Five isolates were from rectal swabs of colonized patients and five from blood cultures of patients with invasive carbapenem-resistant infections. Following microbial identification and antibiotic susceptibility tests, the isolates were subjected to WGS on the Illumina MiSeq platform. All the isolates showed genotypic resistance to tested β-lactams (NDM-1, OXA-1, CTX-M-15, TEM-1B, SHV-1) and other antibiotics. All but one isolate belonged to the ST152 with a novel sequence type, ST3136, differing by a single-locus variant. The isolates had the same plasmid multilocus sequence type (IncF[K12:A-:B36]) and capsular serotype (KL149), supporting the epidemiological linkage between the clones. Resistance to carbapenems in the 10 isolates was conferred by the bla_NDM-1 mediated by the acquisition of multi-replicon [ColRNAI, IncFIB(pB171), Col440I, IncFII, IncFIB(K) and IncFII(Yp)] p18-43_01 plasmid. These findings suggest that the acquisition of bla_NDM-1-bearing plasmid structure (p18-43_01), horizontal transfer and clonal dissemination facilitate the spread of carbapenemases in South Africa. This emphasizes the importance of targeted infection control measures to prevent dissemination.

Keywords: Klebsiella pneumoniae; South Africa; carbapenemase; epidemiology; extensively drug-resistant; genomics; mobile genetic elements; phylogenomic.