Abstract:
Carbapenem-resistant
Klebsiella pneumoniae (CRKP) remains a major clinical pathogen and public health threat with few therapeutic
options. The mobilome, resistome, methylome, virulome and phylogeography of CRKP in South Africa and globally were
characterized. CRKP collected in 2018 were subjected to antimicrobial susceptibility testing, screening by multiplex PCR, genotyping
by repetitive element palindromic (REP)-PCR,
plasmid size, number, incompatibility and mobility analyses, and PacBio’s
SMRT sequencing (n=6). There were 56 multidrug-resistant
CRKP, having blaOXA-48-like
and blaNDM-1/7 carbapenemases on self-transmissible
IncF, A/C, IncL/M and IncX3 plasmids endowed with prophages, traT, resistance islands, and type I and II restriction
modification systems (RMS). Plasmids and clades detected in this study were respectively related to globally established/
disseminated plasmids clades/clones, evincing transboundary horizontal and vertical dissemination. Reduced susceptibility to
colistin occurred in 23 strains. Common clones included ST307, ST607, ST17, ST39 and ST3559. IncFIIk virulent plasmid replicon
was present in 56 strains. Whole-genome
sequencing of six strains revealed least 41 virulence genes, extensive ompK36
mutations, and four different K- and O-loci
types: KL2, KL25, KL27, KL102, O1, O2, O4 and O5. Types I, II and III RMS, conferring
m6A (GATC, GATGNNNNNNTTG, CAANNNNNNCATC motifs) and m4C (CCWGG) modifications on chromosomes and plasmids,
were found. The nature of plasmid-mediated,
clonal and multi-clonal
dissemination of blaOXA-48-like
and blaNDM-1 mirrors epidemiological
trends observed for closely related plasmids and sequence types internationally. Worryingly, the presence of both
blaOXA-48 and blaNDM-1 in the same isolates was observed. Plasmid-mediated
transmission of RMS, virulome and prophages influence
bacterial evolution, epidemiology, pathogenicity and resistance, threatening infection treatment. The influence of RMS on
antimicrobial and bacteriophage therapy needs urgent investigation.
