Scholarlink

<p>ESKAPE pathogens-induced meningitis seriously threatens human health due to antimicrobial resistance and low permeability of blood-brain barrier (BBB). It’s a promising strategy to combat drug-resistant pathogens using synthetic mimics of host defense peptide (HDP) bearing positive charges that are mainly provided by amine or guanidine. Here, we report that biguanide serves as a type of positively charged moiety to design HDP mimics. Biguanide exerts a stronger interaction with bacterial membrane phospholipids via bidentate hydrogen bonds than do amine and guanidine. The biguanide-functionalized HDP mimic, PBGProOx<sub>20</sub>, targets bacterial membrane phospholipids to show potent activity against all ESKAPE pathogens and does not induce antimicrobial resistance. PBGProOx<sub>20</sub> exhibits promising BBB-penetrating property and displays potent therapeutic effects in female mice full-thickness infection model, sub-cutaneous infection model, kidney infection model, peritonitis model, and meningitis model. This study provides a promising strategy for designing HDP mimics to combat ESKAPE pathogens and meningitis.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Biguanide-functionalized peptide mimics effectively combat drug-resistant ESKAPE pathogens and meningitis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月9日

查看全文
  • Weinan Jiang,
  • Min Zhou,
  • Kang Chen,
  • Ximian Xiao,
  • Jia Shi,
  • Haodong Zhang,
  • Jiayang Xie,
  • Sheng Chen,
  • Minzhang Chen,
  • Zihao Cong,
  • Longqiang Liu,
  • Yueming Wu,
  • Runhui Liu

摘要

ESKAPE pathogens-induced meningitis seriously threatens human health due to antimicrobial resistance and low permeability of blood-brain barrier (BBB). It’s a promising strategy to combat drug-resistant pathogens using synthetic mimics of host defense peptide (HDP) bearing positive charges that are mainly provided by amine or guanidine. Here, we report that biguanide serves as a type of positively charged moiety to design HDP mimics. Biguanide exerts a stronger interaction with bacterial membrane phospholipids via bidentate hydrogen bonds than do amine and guanidine. The biguanide-functionalized HDP mimic, PBGProOx20, targets bacterial membrane phospholipids to show potent activity against all ESKAPE pathogens and does not induce antimicrobial resistance. PBGProOx20 exhibits promising BBB-penetrating property and displays potent therapeutic effects in female mice full-thickness infection model, sub-cutaneous infection model, kidney infection model, peritonitis model, and meningitis model. This study provides a promising strategy for designing HDP mimics to combat ESKAPE pathogens and meningitis.