A Model for Transposition of the Colistin Resistance Gene mcr-1 by ISApl1

Area of Science:

• Microbiology
• Genetics
• Molecular Biology

Background:

• The emergence and spread of antimicrobial resistance (AMR) is a significant global health threat.
• The mcr-1 gene confers resistance to colistin, a critical last-resort antibiotic.
• Understanding the genetic mechanisms of mcr-1 mobilization is crucial for controlling its dissemination.

Purpose of the Study:

• To investigate the DNA elements and mechanisms responsible for the mobilization of the mcr-1 gene.
• To characterize the structure of the DNA segment associated with mcr-1.
• To elucidate the role of ISApl1 in mcr-1 transposition.

Main Methods:

• Bioinformatic analysis of mcr-1-containing DNA sequences.
• Comparative sequence analysis to identify conserved DNA segments.
• Investigating the flanking regions and potential mobile genetic elements.

Main Results:

• A common approximately 2,607-bp DNA segment was identified in mcr-1-containing sequences.
• This DNA segment is frequently flanked by the ISApl1 insertion sequence.
• Evidence suggests mcr-1 is mobilized by an ISApl1 composite transposon, which may undergo partial or complete loss of ISApl1 copies.
• mcr-1 mobilization can occur via a single upstream ISApl1 copy and remnants of a downstream ISApl1.

Conclusions:

• The ISApl1 composite transposon is a key player in the mobilization of the mcr-1 gene.
• The plasticity of the ISApl1 composite transposon, including potential loss of ISApl1 copies, contributes to the adaptability of mcr-1 dissemination.
• These findings provide insights into the genetic mobility of mcr-1, aiding in the development of strategies to combat colistin resistance.