期刊
ENVIRONMENTAL MICROBIOLOGY
卷 23, 期 2, 页码 844-860出版社
WILEY
DOI: 10.1111/1462-2920.15171
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资金
- National Natural Science Foundation of China [31830001]
- National Key R&D Program of China [2017YFD0500202]
- national 'Young 1000 talents' Award of China
MCR-4 and MCR-8 are new members of the ongoing MCR family of colistin resistance, while NMCR-2 is identified as a possible progenitor of MCR-8 with similar actions and mechanisms.
MCR-4 and MCR-8 are two recently identified members of an ongoing MCR family of colistin resistance. Although that aquatic reservoir for MCR-4 is proposed, the origin and mechanism of MCR-8 is poorly understood. Here we report a previously unrecognized non-mobile colistin resistance enzyme, termed NMCR-2, originating from the plant pathogenKosakonia pseudosacchari. NMCR-2 (551aa) gives 67.3% identity to MCR-8 (565aa). NMCR-2 is placed as a progenitor/ancestor for MCR-8 in phylogeny of MCR members. Genetic study reveals thatnmcr-2is comparable tomcr-8in the ability of producing phenotypic colistin resistance. Biochemical analyses determine that these two enzymes catalyse the transfer of PEA from the donor PE lipid substrate to the recipient lipid A molecule by a putative 'ping-pong' trade-off. Further experiment of protein engineering demonstrates that the two motifs (TM region and catalytic domain) of NMCR-2 are functionally exchangeable with that of MCR-8, rather than MCR-1. Physiological impacts ofnmcr-2and/ormcr-8are detected inEscherichia coli, featuring with fitness cost. Evidently, the action and mechanism of NMCR-2 is analogous to that of MCR-8. Therefore, our finding underlines that NMCR-2 might be a possible progenitor of MCR-8.
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