Language
English
Publication Date
10-1-2023
Journal
Current Opinion in Structural Biology
DOI
10.1016/j.sbi.2023.102647
PMID
37399693
PMCID
PMC10527939
PubMedCentral® Posted Date
10-1-2024
PubMedCentral® Full Text Version
Author MSS
Abstract
Polymyxins, a last resort antibiotic, target the outer membrane of pathogens and are used to address the increasing prevalence of multidrug-resistant Gram-negative bacteria. The plasmid-encoded enzyme MCR-1 confers polymyxin resistance to bacteria by modifying the outer membrane. Transferable resistance to polymyxins is a major concern; therefore, MCR-1 is an important drug target. In this review, we discuss recent structural and mechanistic aspects of MCR-1 function, its variants and homologs, and how they are relevant to polymyxin resistance. Specifically, we discuss work on polymyxin-mediated disruption of the outer and inner membranes, computational studies on the catalytic mechanism of MCR-1, mutagenesis and structural analysis concerning residues important for substrate binding in MCR-1, and finally, advancements in inhibitors targeting MCR-1.
Keywords
Polymyxins, Colistin, Escherichia coli Proteins, Drug Resistance, Bacterial, Anti-Bacterial Agents, Biology
Published Open-Access
yes
Recommended Citation
Isabel Cristina Materon and Timothy Palzkill, "Structural Biology of Mcr-1-Mediated Resistance to Polymyxin Antibiotics" (2023). Faculty, Staff and Students Publications. 6551.
https://digitalcommons.library.tmc.edu/baylor_docs/6551