The global distribution and spread of the mobilized colistin resistance gene mcr-1

Area of Science:

• Microbiology and Molecular Biology
• Genomics and Bioinformatics
• Public Health and Epidemiology

Background:

• Colistin is a last-resort antibiotic for carbapenem-resistant Enterobacteriaceae (CRE) infections.
• The emergence and spread of plasmid-mediated colistin resistance, particularly the mcr-1 gene, represent a significant global health threat.
• Effective monitoring and surveillance are crucial to combat the dissemination of antibiotic resistance.

Purpose of the Study:

• To characterize the global distribution and evolutionary history of the mcr-1 gene.
• To identify the genetic elements and mechanisms driving the spread of mcr-1.
• To provide a systematic phylogenetic analysis of mcr-1's origin and dissemination.

Main Methods:

• Phylogenetic analysis of 457 mcr-1-positive sequenced isolates.
• Comparative genomics to identify common genetic backgrounds and associated mobile genetic elements.
• Molecular clock analysis to estimate the timing of mcr-1 mobilization and expansion.

Main Results:

• The mcr-1 gene was detected across diverse plasmid types, indicating versatile dissemination.
• A common genetic background was identified across all analyzed mcr-1 sequences.
• Phylogenetic analyses traced the origin of circulating mcr-1 elements to a single mobilization event by the ISApl1 transposon between 2002-2008.
• A significant demographic expansion following this event led to the current global distribution of mcr-1.

Conclusions:

• The global spread of mcr-1 originated from a single, specific mobilization event approximately two decades ago.
• Understanding the movement of antibiotic resistance genes across genomic levels is vital for public health.
• Continuous surveillance and phylogenetic studies are essential to track and control the spread of antimicrobial resistance.