Molecular mechanisms of polymyxin resistance and detection of mcr genes

Area of Science:

• Microbiology
• Molecular Biology
• Genetics

Background:

• Antibiotic resistance poses a significant global health challenge, with increasing numbers of bacteria becoming resistant to major antibiotics.
• Polymyxins are crucial bactericidal antibiotics effective against Gram-negative bacteria, but resistance is a growing concern.
• Mechanisms of polymyxin resistance include intrinsic, mutational, adaptive, and recently discovered horizontally acquired resistance.

Purpose of the Study:

• To review bacterial strategies for developing enhanced resistance to polymyxins.
• To highlight the role of outer membrane changes, efflux pumps, and other resistance determinants.
• To introduce novel in silico tested primers for PCR assays to detect plasmid-encoded mcr genes responsible for colistin resistance.

Main Methods:

• Literature review of polymyxin resistance mechanisms in bacteria.
• Analysis of genetic and molecular strategies contributing to resistance.
• In silico design and testing of primers for PCR-based detection of mcr genes.

Main Results:

• Bacteria employ diverse strategies to resist polymyxins, involving alterations in the outer membrane and increased efflux.
• Horizontally acquired resistance mechanisms, particularly plasmid-mediated mcr genes, are critical for colistin resistance.
• Novel PCR primers have been developed for efficient detection of mcr genes in colistin-resistant isolates.

Conclusions:

• Understanding the genetic basis of polymyxin resistance is vital for developing new antimicrobial agents.
• The identification of novel resistance mechanisms necessitates continuous surveillance and the development of rapid detection methods.
• The developed PCR assay can aid in combating the spread of colistin resistance by enabling quick identification of resistant strains.