Genetic framework and evolutionary dynamics of mcr-positive Klebsiella pneumoniae from 2000 to 2023

The international transmission of the colistin resistance gene mcr in Enterobacteriaceae poses significant public health burdens, while the understanding of the population structure and evolutionary history of mcr -positive Klebsiella pneumoniae worldwide remains unclear. Here, we conducted a genomic analysis on 463 sequences of K. pneumoniae harboring mcr genes from public database between 2000 and 2023. A total of 6 mcr variants ( mcr-1 , - 2 , - 3 , - 8 to - 10 ) were detected, with mcr - 9 (36.1%), mcr - 1 (33.7%) and mcr - 8 (29.2%) genes being the most common. 43.4% of total isolates (201/463) carried carbapenemase genes ( bla NDM , bla KPC , bla IMP , bla OXA-48/181/232 , bla VIM and bla GES ) and 15.3% of isolates (71/463) contained hypervirulent genes ( iucA or iroB ). Correlation analysis indicated mcr - 1 / 8 / 9 genes were positively correlated with specific genomic elements that were rarely described, including mcr - 1 with iucABC and iutA; mcr - 8 with oqxB; mcr-9 with dfrA19 , IS Esa and repA (R absolute value > 0.3, p<0.01). The population of K. pneumoniae can be classified into 6 clusters, some isolates co-harboring mcr and carbapenemase genes exhibited high level of genetic similarity and dispersed in several countries, indicating the possibility of clonal transmission. mcr - 9 gene was introduced into K. pneumoniae in 1978 before the time of mcr - 1 gene in 1988 and mcr - 8 gene in 1993. We found mcr - 1 / 8 / 9 genes in K. pneumoniae evolved high-risk lineages in specific geographical location (China, Thailand and the United Kingdom) that most isolates typically contained iucA, bla NDM or bla KPC . This study highlighted that continuous surveillance for the evolution of mcr -positive K. pneumoniae harboring iucA or carbapenemase genes is essential.