Molecular Insights into Functional Differences between mcr-3- and mcr-1-Mediated Colistin Resistance.

ABSTRACT: The global emergence of plasmid-mediated colistin resistance genes mcr-1 and mcr-3 has threatened the role of the "last-resort" drug colistin in the defense against infections caused by multidrug-resistant Gram-negative bacteria. However, functional differences between these two genes in mediating colistin resistance remain poorly understood. Protein sequence alignment of MCR-3 and MCR-1 was therefore conducted in Clustal Omega to identify sequence divergence. The molecular recognition of lipid A head group phosphatidylethanolamine and MCR-3 enzyme was studied by homology modeling and molecular docking, with the catalytic mechanism of MCR-3 also being explored. Thr277 in MCR-3 was validated as the key amino acid residue responsible for the catalytic reaction using site-directed mutagenesis

SUBMITTER: Li H 

PROVIDER: S-EPMC6125512 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature