Emergence of a novel mobile colistin resistance gene, mcr-8 , in NDM-producing Klebsiella pneumoniae

• DOI: 10.1038/s41426-018-0124-z
• Publication Date: 2018-06-30T06:24:41Z
• Authors: Xiaoming Wang; Yao Wang; Ying Zhou; Jiyun Li; Wenjuan Yin; Shaolin Wang; Suxia Zhang; Jianzhong Shen; Zhangqi Shen; Yang Wang
• Keywords: Models, Molecular; 0301 basic medicine; 0303 health sciences; Colistin; Protein Conformation; Microbial Sensitivity Tests; Article; beta-Lactam Resistance; beta-Lactamases; Anti-Bacterial Agents; Klebsiella Infections; 3. Good health; Klebsiella pneumoniae; 03 medical and health sciences; Conjugation, Genetic; Escherichia coli; Humans; Position-Specific Scoring Matrices; Amino Acid Sequence; Phylogeny

The rapid increase in carbapenem resistance among gram-negative bacteria has renewed focus on the importance of polymyxin antibiotics (colistin or polymyxin E). However, the recent emergence of plasmid-mediated colistin resistance determinants (mcr-1, -2, -3, -4, -5, -6, and -7), especially mcr-1, in carbapenem-resistant Enterobacteriaceae is a serious threat to global health. Here, we characterized a novel mobile colistin resistance gene, mcr-8, located on a transferrable 95,983-bp IncFII-type plasmid in Klebsiella pneumoniae. The deduced amino-acid sequence of MCR-8 showed 31.08%, 30.26%, 39.96%, 37.85%, 33.51%, 30.43%, and 37.46% identity to MCR-1, MCR-2, MCR-3, MCR-4, MCR-5, MCR-6, and MCR-7, respectively. Functional cloning indicated that the acquisition of the single mcr-8 gene significantly increased resistance to colistin in both Escherichia coli and K. pneumoniae. Notably, the coexistence of mcr-8 and the carbapenemase-encoding gene blaNDM was confirmed in K. pneumoniae isolates of livestock origin. Moreover, BLASTn analysis of mcr-8 revealed that this gene was present in a colistin- and carbapenem-resistant K. pneumoniae strain isolated from the sputum of a patient with pneumonia syndrome in the respiratory intensive care unit of a Chinese hospital in 2016. These findings indicated that mcr-8 has existed for some time and has disseminated among K. pneumoniae of both animal and human origin, further increasing the public health burden of antimicrobial resistance.