Regional circulation of blaNDM-1 by CC147 members of Klebsiella pneumoniae: Does it resemble a Relay Race?

Certain clonal complexes (CC) of Klebsiella pneumoniae such as CC147 (ST147, ST392) are major drivers of blaNDM dissemination across the world. Understanding the mechanisms of blaNDM circulation among K.pneumoniae population will help to design better preventing strategies. Comparative genomic analysis of 51 carbapenem non-susceptible strains as well as three hypervirulent K.pneumoniae (hvKp) recovered during 16-months surveillance was performed and the strains were analyzed with XX publicly available ST147/NDM+ genomes. While blaOXA-48 which harboured by IncL/M plasmid was distributed among divergent clones, blaNDM-1 was circulated by twenty of 25 CC147 dominant clone and were mostly recovered from the ICU. While NDM-1 core structure was bracketed by a single isoform of mobile genetic elements (MGEs) [?ISKpn26-NDM-TnAs3-?IS3000-Tn5403] and was located on Col440I plasmid in 68.7% of ST392, different arrangements of MGEs including MITESen1/ISSen4/IS903B/IS5/ISEhe3 on IncFIb(pB171) was identified in ST147 strains. During 2015, ST392 circulated the blaNDM-1 and was gradually replaced by ST147 from the mid to the end of sample collection in 2016. The ST147 strains showed high genetic similarity with four public genomes which harboured blaNDM-1 on the same replicon type. The iucA-D and iroBCDN operons were detected in two ST86 and one ST2159 hvKp, however yersiniabactins were identified among varied STs and in association with different ICEs. Hospitalized patients were found to have multiple transmission patterns, including horizontal transfer of resistance genes between different STs and the clonal dissemination of convergent strains. This is the first analyses of circulating ST147/NDM+ clone in the global context from Iran.