A blaOXA-181-harbouring multi-resistant ST147 Klebsiella pneumoniae isolate from Pakistan that represent an intermediate stage towards pan-drug resistance

Abstract

Carbapenem resistant Klebsiella pneumoniae (CR-KP) infections are an ever-increasing global issue, especially in the Indian subcontinent. Here we report genetic insight into a blaOXA-181 harbouring Klebsiella pneumoniae, belonging to the pandemic lineage ST147, that represents an intermediate stage towards pan-drug resistance. The CR-KP isolate DA48896 was isolated from a patient from Pakistan and was susceptible only to tigecycline and colistin. It harboured blaOXA-181 and was assigned to sequence type ST147. Analysis from whole genome sequencing revealed a very high sequence similarity to the previously sequenced pan-resistant K. pneumoniae isolate MS6671 from the United Arab Emirates. The two isolates are very closely related with only 46 chromosomal nucleotide differences, 14 indels and differences in plasmid content. Both carry a substantial number of plasmid-borne and chromosomally encoded resistance determinants. Interestingly, the two differences in susceptibility between the isolates could be attributed to DA48896 lacking an insertion of blaOXA-181 into the mgrB gene that results in colistin resistance in MS6671 and SNPs affecting AcrAB efflux pump expression likely to result in tigecycline resistance. These differences between the otherwise very similar isolates indicate that strong selection has occurred for resistance towards these last-resort drugs and illustrates the trajectory of resistance evolution of OXA-181-producing versions of the ST147 international risk clone.

Molecular characteristics of carbapenemase-producing Enterobacterales in the Netherlands; results of the 2014–2018 national laboratory surveillance

“…The predominant classical MLST type among bla OXA-181carrying K. pneumoniae and E. coli isolates were ST147 and ST410, respectively. These sequence types are known to circulate around the world [20,21], which might be reflected by the increasing occurrence of bla OXA-181 in the Netherlands. Another carbapenemase allele worth noting is bla VIM-1 , which until 2016 was found rarely among Enterobacterales in the Netherlands and globally [22], but was found 25 times in 2017, 11 of which belonged to an outbreak.…”

Coexistence of Two blaNDM–5 Genes Carried on IncX3 and IncFII Plasmids in an Escherichia coli Isolate Revealed by Illumina and Nanopore Sequencing

“…The 52-kb backbone of pNDM5-GZ04_B contained a set of core genes for plasmid replication (repA), conjugation/T4SS (tra and trb genes), stability (stdB) and segregation (parM). This backbone was highly identical to those of F2:A-:B-plasmids (Pu et al, 2016;Nahid et al, 2017;Shin et al, 2017) including pCC1410-2 but lacked a 5-kb region carrying the psiA, psiB, spo0J and ssbF genes associated with plasmid SOS inhibition, partition and recombination.…”

Antibiotic Resistance and Mobile Genetic Elements in Extensively Drug-Resistant Klebsiella pneumoniae Sequence Type 147 Recovered from Germany

“…The expansion of high-risk K. pneumoniae clones with a multidrug-resistant (MDR) or extensive drug-resistant (XDR) phenotype has been observed in recent years [ 4 ]. K. pneumoniae ST147 has been reported as an emerging high-risk clone associated with plasmid-encoded extended-spectrum β-lactamases (ESBLs) like bla CTX-M-15, or carbapenemases such as bla OXA-48 and bla NDM-1 [ 4 , 12 , 13 , 14 , 15 , 16 , 17 ].…”