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Updated: Jan 30, 2026

Characterizing Herbivore Resistance Mechanisms: Spittlebugs on Brachiaria spp. as an Example
Published on: June 19, 2011
Action and mechanism of the colistin resistance enzyme MCR-4
Huimin Zhang1,2,3, Mengyun Hou1,2, Yongchang Xu1,2
11Department of Pathogen Biology & Microbiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058 China.
Abstract:
Colistin is the last-resort antibiotic against lethal infections with multidrug-resistant bacterial pathogens. A rainbow coalition of mobile colistin resistance (mcr) genes raises global health concerns. Here, we describe the action and mechanism of colistin resistance imparted by MCR-4, a recently-identified member from the broader MCR family. We found that MCR-4 originates from the silenced variant of Shewanella frigidimarina via progressive evolution and forms a phylogenetically-distinct group from the well-studied MCR-1/2 family. Domain-swapping experiments further confirmed that MCR-1 and MCR-4 transmembrane and catalytic domains are not functionally-interchangeable. However, structural and functional analyses demonstrated that MCR-4 possesses a similar PE lipid substrate-recognizable cavity and exploits an almost-identical ping-pong catalysis mechanism. MCR-4 also can alleviate colistin-triggered accumulation of reactive oxygen species (ROS). Taken together, this finding constitutes a functional proof that MCR-4 proceeds in a distinct evolutionary path to fulfill a consistent molecular mechanism, resulting in phenotypic colistin resistance.
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