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Identification of Antibacterial Immunity Proteins in Escherichia coli using MALDI-TOF-TOF-MS/MS and Top-Down Proteomic Analysis
Published on: May 23, 2021
The Biology of Colicin M and Its Orthologs
Dimitri Chérier1,2, Delphine Patin1, Didier Blanot1
1Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Saclay, 91198 Gif-sur-Yvette, France.
Abstract:
The misuse of antibiotics during the last decades led to the emergence of multidrug resistant pathogenic bacteria. This phenomenon constitutes a major public health issue. Consequently, the discovery of new antibacterials in the short term is crucial. Colicins, due to their antibacterial properties, thus constitute good candidates. These toxin proteins, produced by E. coli to kill enteric relative competitors, exhibit cytotoxicity through ionophoric activity or essential macromolecule degradation. Among the 25 colicin types known to date, colicin M (ColM) is the only one colicin interfering with peptidoglycan biosynthesis. Accordingly, ColM develops its lethal activity in E. coli periplasm by hydrolyzing the last peptidoglycan precursor, lipid II, into two dead-end products, thereby leading to cell lysis. Since the discovery of its unusual mode of action, several ColM orthologs have also been identified based on sequence alignments; all of the characterized ColM-like proteins display the same enzymatic activity of lipid II degradation and narrow antibacterial spectra. This publication aims at being an exhaustive review of the current knowledge on this new family of antibacterial enzymes as well as on their potential use as food preservatives or therapeutic agents.
Insights
New antibacterial enzymes, Colicin M (ColM) and its variants, target essential bacterial cell wall precursors. These findings offer novel strategies against multidrug-resistant bacteria and potential applications in food preservation.
Area of Science:
- Microbiology
- Biochemistry
- Molecular Biology
Background:
- Antibiotic misuse has accelerated the rise of multidrug-resistant bacteria, posing a significant global health threat.
- Novel antibacterial agents are urgently needed to combat resistant pathogens.
- Colicins, bacteriocins produced by E. coli, exhibit potent antibacterial activity and are promising candidates for new antimicrobial therapies.
Purpose of the Study:
- To provide a comprehensive review of Colicin M (ColM) and related enzymes.
- To explore the unique mechanism of ColM in degrading peptidoglycan precursors.
- To assess the potential of ColM-like proteins as therapeutic agents and food preservatives.
Main Methods:
- Literature review of existing research on Colicin M and its orthologs.
- Analysis of sequence alignments to identify ColM-like proteins.
- Examination of the enzymatic activity and antibacterial spectra of characterized ColM variants.
Main Results:
- Colicin M is the only known colicin that inhibits peptidoglycan biosynthesis by hydrolyzing lipid II.
- ColM-like proteins share the same lipid II degradation activity but possess narrow antibacterial spectra.
- Several ColM orthologs have been identified, highlighting a new family of antibacterial enzymes.
Conclusions:
- Colicin M and its variants represent a novel class of antibacterial enzymes with a unique mechanism of action.
- These enzymes hold potential for developing new treatments against multidrug-resistant bacteria.
- Further research into ColM-like proteins could lead to applications in food preservation and novel therapeutics.
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