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CG258 is the dominant carbapenemase-producing  Klebsiella pneumoniae  clone worldwide and treatment of infections caused by this clone relies largely on the last-line antibiotics, colistin, and tigecycline. However, the emergence and global dissemination of  mcr  and  tmexCD1 - toprJ1  genes have significantly compromised their clinical applications. CG258  K. pneumoniae  carrying both  mcr  and  tmexCD1 - toprJ1  have not been reported. A colistin-resistant strain T698-1 belonging to ST1326, a member of CG258, was isolated from the intestinal sample of a patient and characterized by the antimicrobial susceptibility testing, conjugation assay, WGS and bioinformatics analysis. It was resistant to colistin, tetracycline, aminoglycoside, fluoroqinolone, phenicols, sulfonamide, and some β-lactams, and positive for  mcr-8.2 ,  tmexCD1 - toprJ1 , and ESBL genes ( bla   DHA– 1  and  bla   CTX–M– 15 ). The  tmexCD1 - toprJ1  gene cluster was located in an multi-drug resistant (MDR) region flanked by Tn As1  elements on an IncHI1B/FIB plasmid. The genetic context of  tmexCD1 - toprJ1  was slightly distinct from previously reported Tn 5393 -like structures, with an IS 26  element disrupting the upstream Tn 5393  and its adjacent genetic elements. The  mcr-8.2  gene was inserted into the backbone of an IncFII/FIA plasmid with the genetic context of IS Ecl1 - mcr-8.2 - orf -IS Kpn26 . To our knowledge, this is the first report of co-occurrence of  mcr-8.2  and  tmexCD1 - toprJ1  in a CG258  K. pneumoniae  strain. Though this strain is tigecycline sensitive, the acquisition of colistin and tigecycline resistance determinants by the endemic CG258  K. pneumoniae  clone still poses a serious public health concern. CG258, which became resistant to multiple last resort antibiotics, would be the next emerging superbug.

frontiers in microbiology

Emergence of an ST1326 (CG258) Multi-Drug Resistant Klebsiella pneumoniae Co-harboring mcr-8.2, ESBL Genes, and the Resistance-Nodulation-Division Efflux Pump Gene Cluster tmexCD1-toprJ1 in China