Conjugation as an evolutionary bottleneck in antimicrobial resistance spread

Area of Science:

• Microbiology
• Genetics
• Evolutionary Biology

Background:

• Antimicrobial resistance (AMR) is a major global health threat.
• Current understanding of AMR focuses on mutation and selection, which doesn't fully explain rapid resistance spread.
• Horizontal gene transfer, particularly conjugation, plays a critical role in AMR dissemination.

Purpose of the Study:

• To reframe AMR as an amplification problem driven by conjugation.
• To explore conjugation as a rate-limiting step and a therapeutic target for AMR control.
• To review current and emerging strategies for disrupting conjugation and controlling AMR.

Main Methods:

• Literature review synthesizing evidence on conjugation dynamics and AMR spread.
• Analysis of trade-offs influencing conjugation efficiency and plasmid persistence.
• Examination of adaptive plasmid features and their impact on AMR dissemination.

Main Results:

• Conjugation, mediated by plasmids, is a primary driver of AMR amplification and spread.
• Conjugation efficiency is constrained by trade-offs, making it a rate-limiting step.
• Plasmids possess adaptive mechanisms that enhance their persistence and complicate control efforts.

Conclusions:

• Targeting horizontal gene transfer (conjugation) is a viable strategy to control AMR.
• Disrupting conjugation can limit the spread of resistance genes, complementing efforts to prevent their emergence.
• Interventions focused on controlling gene flow offer a pathway to contain AMR expansion.