Genomic path to pandrug resistance in a clinical isolate of Klebsiella pneumoniae.

Carbapenem-resistant Klebsiella pneumoniae have spread globally throughout tertiary hospitals. Many Carbapenem-resistant K. pneumoniae clinical isolates are multidrug-resistant (MDR) and may become eventually pandrug-resistant (PDR). Here we present the closed genome of a PDR VIM-1-producing K. pneumoniae strain (KP1050) obtained in a tertiary hospital. The isolate belonged to sequence type 54 (ST54) and had five extrachromosomal elements (four plasmids and a circular phage genome). Most of the antimicrobial resistance genes (ARGs) were located in two clusters borne by two of the plasmids, comprising a class 1 integron that contained up to 14 ARGs including a VIM-1 metallo-ß-lactamase gene, and an IS26 transposon that contained a mobile element from Acinetobacter baumannii encoding the amikacin resistance gene aac(6')-Ian. A MDR isolate obtained 6 years previously was identified (KP1048) retrospectively and was sequenced. Comparison of the two genomes showed that chromosomal mutations in outer membrane porins as well as mutations in the ramR and phoQ genes contributed to increase the resistance spectrum.