Molecular Mechanisms of Colistin Resistance in in a Tertiary Care Teaching Hospital.

Background: Over the last two decades, the prevalence of colistin resistance among the members of has been increasing, particularly among isolates; this limits the potential use of colistin and leads to worsened clinical outcomes.

Methods: We investigated the prevalence and genetic characteristics of colistin-resistant (COLR-KP) in clinical isolates using genomic sequencing.

Results: In total, 53 K isolates (4.5%, 53/1,171) were confirmed as COLR-KP, of which eight isolates carried mobile colistin-resistant () gene. Although the overall prevalence rate (0.7%, 8/1,171) of -like genes in clinical remained relatively low, the presence of (15.1%, 8/53) among the COLR-KP isolates indicated that the mobile resistance gene was already widespread among isolates in hospital setting. We randomly selected 13 COLR-KP isolates (four -bearing and nine non--bearing isolates) for whole-genome sequencing, including two pandrug-resistant and four sequence type 11 (ST11) isolates. Phylogenetic analysis revealed that all COLR-KP isolates were genetically diverse. Among the four -bearing isolates, three (KP4, KP18, and KP30) were positive for and one (KP23) for ; none of the other genes were detected. The in the KP4 and KP30 isolates were located in an plasmid (approximately 33 kb) and could be successfully transferred to J53AZ. In contrast, for the -bearing plasmid in KP23 (), colistin resistance could not be transferred by conjugation. The mcr-1-producing isolate KP18 coexists a novel plasmid-carried tigecycline resistance gene tmexCD1-toprJ1. The most common chromosomal mutation associated with colistin resistance was a T246A amino acid substitution in PmrB, which was identified in most COLR-KP isolates (11/13, 84.6%). All ST11 isolates additionally had an R256G amino acid substitution. Critical virulence factors associated with hypervirulent were detected in four COLR-KP isolates; these virulence factors included aerobactin, salmochelin, and yersiniabactin.

Conclusion: We found that -bearing COLR-KP emerged in our hospital and was growing at an increasing rate. Simultaneous emergence of hypervirulence and colistin-tigecycline-carbapenem resistance in the epidemic clone ST11 was also observed; this highlights the significance of active and continuous surveillance.