Comparative analysis of the Colistin resistance-regulating gene cluster in Klebsiella species

CrrAB two-component regulatory system is associated with colistin resistance in Klebsiella pneumoniae . Recently, some K. pneumoniae isolates lacking crrAB genes have been identified. In this study, we investigated the distribution and structural variation of the crrBAC-kexD cluster. To evaluate the structural variation of the crrBAC-kexD cluster, we explored 59 clinical K. pneumoniae isolates from Korea, and 508 whole genomes of K. pneumoniae and other strains of Klebsiella sp. Significant structural variations in crrBAC-kexD and its surrounding regions were identified among K. pneumoniae genomes. Within the genus Klebsiella , the cluster was identified only in K. pneumoniae , K. variicola , and K. quasipneumoniae , which form the K. pneumoniae complex. Among the 304 available K. pneumoniae genomes, an intact crrBAC-kexD cluster was identified in 178 isolates (58.6%), while the cluster was absent in 90 isolates (29.6%). Partial deletions within the cluster were identified in 22 genomes (7.2%). The most diverse structural patterns of the crrBAC-kexD cluster were observed in ST11 strains. Some clades lacked the crrBAC-kexD cluster. The crrBAC-kexD cluster was identified in the genomes of other bacterial species, including Citrobacter freundii and Enterobacter ludwigii. The crrBAC-kexD cluster is proposed to have been acquired by the ancestor of the K. pneumoniae complex from other bacterial species and the cluster may have been lost and re-acquired repeatedly in K. pneumoniae strains according to the phylogenetic analysis. The dynamic evolution of the crrBAC-kexD cluster suggests that it may have other roles, in addition to colistin resistance, in bacterial physiology.