Pusan National University: Beyond Antibiotics--A Paradigm Shift Toward Bacteria-Control-Centric Therapies

Novel extracellular vesicle platform helps polymyxins kill multidrug-resistant gram-negative bacteria at lower and potentially safer doses

BUSAN, South Korea, July 23, 2026 /PRNewswire/ -- Antimicrobial resistance is a major global health threat, with multidrug resistant (MDR) gram- negative bacteria reducing the effectiveness of last-line antibiotics and increasing mortality. Polymyxins are among the few antibiotics available to treat 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 enhances antibiotic susceptibility, enabling lower doses without compromising efficacy. This transformative approach shifts the focus from antibiotic-centric to bacteria-control-centric therapy by facilitating membrane gateways that enhance antibiotic uptake in bacteria.

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.

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, researchers 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.

The researchers then engineered extracellular vesicles (EVs) carrying both TimP and polymyxin B (PMB), creating a targeted delivery platform called PMB@TimP EVs. Acting as a "Trojan-horse drug delivery system," the vesicles delivered the antibiotic directly to bacteria by making the bacterial membrane easier for the drug to penetrate.

Further analysis showed that PMB@TimP EVs enhanced bacterial killing, remained stable across a broader pH range, and caused minimal toxicity to mammalian cells compared with free PMB. In a murine model of sepsis caused by MDR E. coli, the engineered vesicles improved survival where free PMB failed. Safety studies found no abnormal accumulation in major organs, with inflammatory markers and liver enzymes remaining normal.

The team found that LamB, the bacterial outer membrane protein required for TimP activity, is conserved in Salmonella Typhimurium. This finding suggests the broader applicability of the platform against MDR gram-negative bacteria.

"PMB@TimP EVs can serve as a potent adjuvant therapy for patients suffering from sepsis, pneumonia, or urinary tract infections caused by MDR gram-negative bacteria, significantly improving recovery rates," says Prof. Kim.

These findings require further safety and efficacy studies against a broader range of resistant bacterial infections before human clinical trials.

"Within 5-10 years, this platform could be integrated into standards for combating MDR pathogens. This will ultimately reduce the over-prescription of antibiotics and contribute to a more sustainable healthcare system," concludes Prof. Kim.

Reference
Title of original paper: The sRNA-encoded peptide TimP rewires the Escherichia coli envelope via LamB to sensitize bacteria to polymyxins
Journal: Drug Resistance Updates
DOI: 10.1016/j.drup.2026.101406

About Pusan National University
Website: https://www.pusan.ac.kr/eng/Main.do

Media Contact:
Goon-Soo Kim
82 51 510 7928
[email protected]

SOURCE Pusan National University