Antimicrobial resistance is one of the world's most alarming public health challenges, because the multidrug-resistant (MDR) gram-negative bacteria increasingly render even last-line antibiotics ineffective, leading to substantially higher mortality rates. Polymyxins are a class of antibiotics that remain among the few treatment options available for severe infections caused by resistant Escherichia coli. But their widespread use is limited by serious side effects, including kidney and nerve toxicity.
Driven by this gap, researchers have now developed an innovative strategy that makes bacteria more susceptible to these antibiotics, potentially allowing doctors to use lower, safer doses without sacrificing effectiveness. This transformative approach shifts the focus from antibiotic-centric to bacteria-control-centric therapy rendering bacteria more susceptible to the antibiotics by facilitating membrane gateways that enhance antibiotic uptake.
The research team was led by Professor Kwang-sun Kim from the Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Republic of Korea. This study was made available online on April 22, 2026, and was published in Volume 87 of the journal Drug Resistance Updates on July 01, 2026.
"With the development of new antibiotics failing to keep pace with bacterial evolution, maximizing the efficacy of existing resources will become the primary strategy to bridge the therapeutic gap in clinical settings," says Prof. Kim
Rather than designing another antibiotic to kill bacteria directly, the team identified a naturally occurring peptide called TimP, encoded by a bacterial small non-coding RNA (sRNA) RyfA, that prompts bacteria to reorganize their own outer membrane. This remodeling creates openings that allow polymyxins to penetrate the bacterial envelope more effectively.
The team screened 91 bacterial sRNAs to identify molecules capable of increasing sensitivity to polymyxins and identified RyfA, within which peptide TimP was responsible for dramatically enhancing antibiotic susceptibility. Through structural prediction and in vitro validation, we showed that TimP binds to the outer membrane protein called porin LamB, triggering widespread changes in the bacterial envelope. These changes include increased membrane permeability, higher production of reactive oxygen species, and greater release of extracellular vesicles.
