People's Daily Online, Beijing, Dec. 30 (Reporter: Zhao Zhuaqing) — Bacterial meningitis poses a severe threat to human health. ESKAPE pathogens, a major cause of hospital-acquired infections, have been defined by the World Health Organization (WHO) as priority pathogens requiring critical or high-priority action. The blood-brain barrier (BBB) blocks nearly 100% of large molecules and 98% of small molecules from entering the brain, making the treatment of meningitis particularly difficult. While Host Defense Peptides (HDPs) and their mimetics are considered highly promising candidates against drug-resistant bacterial infections, their application in meningitis research has been hindered by weak broad-spectrum antibacterial activity or an inability to penetrate the BBB.
The Suzhou Institute of Biomedical Engineering and Technology (SIBET) of the Chinese Academy of Sciences has proposed an innovative strategy: "using biguanide as a novel cationic side-chain group for HDP mimetics." Leveraging the high charge density and strong phospholipid binding capacity of the biguanide functional group, the researchers achieved high-efficiency, broad-spectrum membrane-disrupting bactericidal performance against ESKAPE drug-resistant bacteria using biguanide-modified polymers. Furthermore, long-term treatment did not induce bacterial resistance or cross-resistance.
Biguanide-modified peptide mimetics designed based on this strategy have demonstrated excellent therapeutic effects in various animal models, including skin wound, subcutaneous, kidney, and peritonitis infections. More importantly, these mimetics can penetrate the blood-brain barrier via transcytosis, effectively treating drug-resistant bacterial meningitis. This study provides an innovative strategy for designing HDP mimetics that combine potent anti-ESKAPE activity with BBB-penetrating capabilities, holding significant importance for the treatment of ESKAPE infections, including meningitis.
The related research findings were published in Nature Communications. The study was supported by the National Key R&D Program of China and the China Postdoctoral Science Foundation.
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