Magnesium depletion unleashes two unusual modes of colistin resistance with different fitness costs.

ABSTRACT: Increasing bacterial resistance to colistin, a vital last-resort antibiotic, is an urgent challenge. We previously reported that magnesium sequestration by Candida albicans enables Pseudomonas aeruginosa to become colistin-resistant. Here, we show that Mg²⁺ depletion drives P. aeruginosa to evolve greater colistin resistance through genetic changes in lipid A biosynthesis-modification pathways and a putative magnesium transporter. These mutations synergize with the Mg²⁺-sensing PhoPQ two-component signaling system to remodel lipid A structures of the bacterial outer membrane in previously uncharacterized ways. One predominant mutational pathway relies on early mutations in htrB2, a non-essential gene involved in lipid A biosynthesis, which

SUBMITTER: Hsieh YP 

PROVIDER: S-EPMC11507728 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature