Co-existence of two blaNDM-5 and blaOXA-181 on distinct plasmids in a carbapenem-resistant Klebsiella pneumoniae from a tertiary hospital, Tanzania

Abstract

Purpose

To understand the mechanisms of carbapenem-resistant Klebsiella pneumoniae (CRKP) from Tanzania and characterize the genomes carrying the carbapenemase genes.

Methods

Clinical CRKP isolates were selected from ongoing antimicrobial resistance surveillance at Muhimbili National Hospital, Dar es Salaam, Tanzania. Whole-genome sequencing was performed utilizing Illumina and Nanopore platforms.

Results

A total of twelve CRKP were analyzed in this study. Six different multilocus sequence types were detected, six isolates were sequence type ST437 and one belonged to a novel sequence type, ST6258. Resistance to carbapenems was multifactorial with co-existence of bla_NDM-5 and bla_OXA-181 in six CRKP, and bla_NDM-5 and bla_OXA-232 in one isolate, and chromosomal mutation of ompK36 and ompK37 in all twelve isolates. All the CRKP carried genes conferring resistance to 3rd generation cephalosporins, penicillin, aminoglycosides, fosfomycin, trimethoprim-sulfamethoxazole, and quinolones. The hybrid assemblies of 001BS and 002PS2 revealed that they harbored seven and six different plasmids, respectively. The 001BS carried two bla_NDM-5 on distinct plasmids. The first bla_NDM-5 gene was carried on an IncFIB(K) plasmid; and the second bla_NDM-5 co-existed with bla_OXA-181 on the ColPK3-IncX3 plasmid. In contrast, in 002PS2 the bla_NDM-5 and bla_OXA-181 were carried on the IncFIB(K)-IncFII(K) and ColPK3-IncX3 plasmids, respectively. The genetic environment of the bla_NDM-5 gene on both plasmids was flanked by the same genetic core IS26–IS30–bla_NDM-5 –ble–trpF–DsbD–ISCR1–sul1– QacE–IS3000.

Conclusion

Clonally related CRKP ST437 with multiple co-existing carbapenemase genes were detected for the first time at the tertiary hospital in Tanzania. The existence of this high-risk clone poses a great risk for further spread at our facility.