Scholarlink

<p>The growing threat of <i>Staphylococcus aureus</i>, including methicillin resistant strains, calls for therapies that disarm virulence. Staphyloxanthin, a carotenoid pigment, protects <i>S. aureus</i> from oxidative killing and supports immune evasion. Here we identify clemizole, an FDA approved antihistamine, as a direct inhibitor of CrtN, a key enzyme in staphyloxanthin biosynthesis. Clemizole suppresses pigment with an IC<sub>50</sub> of 102.8 nM and inhibits CrtN activity with an IC<sub>50</sub> of 2.57 μM, increasing killing by human whole blood, macrophages, neutrophils&#xa0;and oxidative stress. It remains active in <i>S. aureus</i> and <i>Pseudomonas aeruginosa</i> coculture. Surface plasmon resonance, docking, and mutagenesis confirm CrtN binding. In a murine skin infection model, clemizole reduces bacterial burden, accelerates wound healing, improves tissue architecture, and dampens local and systemic inflammation. These data validate CrtN as a tractable antivirulence target and support clemizole as a scaffold to promote host mediated clearance.</p><p></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

Clemizole inhibits CrtN-driven staphyloxanthin biosynthesis in Staphylococcus aureus to enhance host immune clearance

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月25日

查看全文
  • Hangqian Yu,
  • Kaiyao Zhang,
  • Jinli Ge,
  • Kelong Ma,
  • Shizhen Ma,
  • Hongtao Liu,
  • Qian Li,
  • Jiazhang Qiu

摘要

The growing threat of Staphylococcus aureus, including methicillin resistant strains, calls for therapies that disarm virulence. Staphyloxanthin, a carotenoid pigment, protects S. aureus from oxidative killing and supports immune evasion. Here we identify clemizole, an FDA approved antihistamine, as a direct inhibitor of CrtN, a key enzyme in staphyloxanthin biosynthesis. Clemizole suppresses pigment with an IC50 of 102.8 nM and inhibits CrtN activity with an IC50 of 2.57 μM, increasing killing by human whole blood, macrophages, neutrophils and oxidative stress. It remains active in S. aureus and Pseudomonas aeruginosa coculture. Surface plasmon resonance, docking, and mutagenesis confirm CrtN binding. In a murine skin infection model, clemizole reduces bacterial burden, accelerates wound healing, improves tissue architecture, and dampens local and systemic inflammation. These data validate CrtN as a tractable antivirulence target and support clemizole as a scaffold to promote host mediated clearance.