First report of IS element mediating gene disruption in the ST1 colistin- and carbapenem-resistant cluster isolated from a patient with chest infection.

Unlabelled: Colistin is used as a last-line therapy against carbapenem-resistant (CRKP). However, colistin resistance in is increasingly reported worldwide. This study aims to investigate the instrumental role of insertion sequence (IS) elements in colistin resistance through disruption in during treatment. Five clinical isolates of CRKP, designated KPN1~KPN5 were collected from the lower respiratory tract of a patient with chest infection before and after treatment with colistin. Antimicrobial susceptibility testing was performed using the broth microdilution method. Whole genome sequencing and bioinformatics were used to analyze the sequence types (STs), resistance genes, and genetic characteristics of the five isolates of . Antimicrobial susceptibility testing indicated that all five isolates were resistant to cephalosporins (ceftriaxone, ceftazidime, and cefepime), several carbapenems (imipenem, meropenem), cefoperazone-sulbactam, piperacillin-tazobactam, ciprofloxacin, and fosfomycin, whereas they were sensitive to amikacin and tigecycline. In addition, three of these isolates were resistant to colistin, with minimum inhibitory concentration values of >8 mg/L. Whole genome sequencing revealed that all five isolates belonged to sequence type 1 (ST1), which shared an identical . Notably, disruption of by the IS insertion sequence was shown to be the primary colistin resistance mechanism during the treatment. To our knowledge, this is the first report of IS element mediating disruption in the ST1 colistin and CRKP obtained from a patient with chest infection in mainland China. This study provides new research ideas to explore the clinical drug resistance mechanism of CRKP and the critical need to monitor and understand resistance mechanisms to preserve the efficacy of last-line antibiotics such as colistin.

Importance: Of note, this chapter gives an update on colistin resistance in sequence type 1 , by focusing on the disrupted by IS element.