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

doi:10.3390/microorganisms8010137

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 blaNDM-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 blaNDM-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.

Highlights

The last decade has witnessed a dramatic increase both in the proportion and absolute number of multi-drug resistant bacterial pathogens [1]
Infections caused by extensively drug-resistant (XDR) Gram-negative pathogens have emerged as one of the world’s greatest threats [2], not the least of which are the carbapenem-resistant bacteria that are on the rise globally [3,4,5]
Five out of the 263 rectal swabs as well as the five blood culture samples obtained from infected patients for comparison, were confirmed as carbapenem-resistant K. pneumoniae (CRKP)

Summary

Introduction

The last decade has witnessed a dramatic increase both in the proportion and absolute number of multi-drug resistant bacterial pathogens [1]. Carbapenems are a potent class of β-lactam antibiotics that are often used as “last-line agents” or “antibiotics of last resort” when infected patients become severely ill or are suspected of harboring resistant bacteria [12] They are considered first-line agents in the treatment of infections caused by extended-spectrum β-lactamase (ESBL)-producing organisms [13]. The alarming global spread of CPE isolates has reached African countries including in Angola, Algeria, Gabon, Mali, Nigeria, and South Africa with NDM-1 and OXA-48 been the most commonly reported carbapenemases [19,20,21,22,23,24]. A total of 760 K. pneumoniae plasmid annotation reports are available at the Pathosystems Resource Integration Center (PATRIC) database (https://www.patricbrc.org/)

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Conclusion