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The global distribution and spread of the mobilized colistin resistance gene mcr-1

By Ruobing Wang, Lucy van Dorp, Liam Shaw, Phelim Bradley, Qi Wang, Xiaojuan Wang, Longyang Jin, Qing Zhang, Yuqing Liu, Adrien Rieux, Thamarai Dorai-Schneiders, Lucy Anne Weinert, Zamin Iqbal, Jeffrey D. Jensen, Hui Wang, Francois Balloux

Posted 17 Nov 2017
bioRxiv DOI: 10.1101/220921 (published DOI: 10.1038/s41467-018-03205-z)

Colistin represents one of the very few available drugs for treating infections caused by carbapenem resistant Enterobacteriaceae (CRE). As such, the recent plasmid-mediated spread of the mobilized colistin resistance gene mcr-1 poses a significant public health threat requiring global monitoring and surveillance. In this work, we characterize the global distribution of mcr-1 using a dataset of 457 mcr-1 positive sequenced isolates consisting of currently publicly available mcr-1 carrying sequences combined with an additional 110 newly sequenced mcr-1 positive isolates from China. We find mcr-1 in a diversity of plasmid backgrounds but identify an immediate background common to all mcr-1 sequences. Our analyses establish that all mcr-1 elements in circulation descend from the same initial mobilization of mcr-1 by an ISApl1 transposon in the mid 2000s (2002-2008; 95% higher posterior density), followed by a dramatic demographic expansion, which led to its current global distribution. Our results provide the first systematic phylogenetic analysis of the origin and spread of mcr-1, and emphasize the importance of understanding the movement of mobile elements carrying antibiotic resistance genes across multiple levels of genomic organization.

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