Within-host acquisition of colistin-resistance of an NDM-producing subsp. strain through the insertion sequence--mediated inactivation of gene in a lung transplant child in China.

Background: Colistin, as the antibiotic of "last resort" for carbapenem-resistant , develop resistance during administration of this antimicrobial agent. We identified an NDM-1-producing subsp. (KQSS) strain KQ20605 recovered from a child, which developed resistance to colistin (KQ20786) through acquiring an IS element between the -27 and -26 bp of promoter region after 6-day colistin usage.

Objectives: The aim of this study is to explore the source of IS in the disruptive gene and its underlying mechanisms.

Materials And Methods: Antibiotics susceptibility testing was conducted microbroth dilution method. The colistin-induced experiment of KQ20605 was performed to mimic the transition from colistin-sensitive to resistant. Whole-genome sequencing was used to molecular identification of colistin resistance mechanism.

Results: The IS element integrated into gene of KQ20786 had a 100% nucleotide identity and coverage match with one IS on plasmid IncR, and only 95.1% (1005/1057) identity to those on chromosome. , upon the pressure of colistin, KQ20605 could also switch its phenotype from colistin-sensitive to resistant with IS elements (e.g., IS and IS) frequently inserted into gene at "hotspots", with the insertion site of IS nearly identical to that of KQ20786. Furthermore, IS elements in this isolate were only encoded by plasmids, including IncR and conjugative plasmid IncN harboring .

Conclusion: Mobilizable IS elements on plasmids tend to be activated and integrated into gene at "hotspots" in this KQSS, thereby causing the colistin resistance emergence and further dissemination.