Scholarlink

<p>Antibiotic resistance is a growing concern, and there is an urgent need for alternative treatments. A proposed solution includes endolysins. Naturally occurring endolysins have limited activity against Gram-negative bacteria due to the presence of an outer membrane. Previous agar-based screening methods did not consider this and screened for activity on autoclaved cell debris. In this study, we used a soft-agar-based screening method to identify endolysins targeting <i>Pseudomonas aeruginosa</i>. This method enabled us to screen for activity of endolysins on live <i>Pseudomonas aeruginosa</i>, taking the outer membrane into account. The application of this randomized forward screening method led to the discovery of three highly bactericidal endolysins, L0779, L0782, and L0799. These endolysins displayed a broad spectrum of activity against other Gram-negative bacterial species. We report minimal inhibitory concentrations (MICs) for endolysins acting on multiple Gram-negative ESKAPE species, with MICs for L0782 on <i>Pseudomonas aeruginosa</i>, <i>Escherichia coli</i>, <i>Klebsiella pneumoniae</i> and <i>Acinetobacter baumannii</i> ranging from 4 to 16&#xa0;µg/mL. In summary, our screening method enables rapid identification of endolysins with broad-spectrum activity against Gram-negative bacteria. These show potential for further development as alternative treatments for antibiotic-resistant infections.</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

Discovery of potent endolysins against Pseudomonas aeruginosa and other gram-negative ESKAPE pathogens by an agar-based screening method

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月11日

查看全文
  • Vera Oberbauer,
  • Michele Mutti,
  • Timo Schwebs,
  • Svetlana Durica-Mitic,
  • Zehra Visram,
  • Donaat Kestemont,
  • Adriana Badarau,
  • Lorenzo Corsini

摘要

Antibiotic resistance is a growing concern, and there is an urgent need for alternative treatments. A proposed solution includes endolysins. Naturally occurring endolysins have limited activity against Gram-negative bacteria due to the presence of an outer membrane. Previous agar-based screening methods did not consider this and screened for activity on autoclaved cell debris. In this study, we used a soft-agar-based screening method to identify endolysins targeting Pseudomonas aeruginosa. This method enabled us to screen for activity of endolysins on live Pseudomonas aeruginosa, taking the outer membrane into account. The application of this randomized forward screening method led to the discovery of three highly bactericidal endolysins, L0779, L0782, and L0799. These endolysins displayed a broad spectrum of activity against other Gram-negative bacterial species. We report minimal inhibitory concentrations (MICs) for endolysins acting on multiple Gram-negative ESKAPE species, with MICs for L0782 on Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii ranging from 4 to 16 µg/mL. In summary, our screening method enables rapid identification of endolysins with broad-spectrum activity against Gram-negative bacteria. These show potential for further development as alternative treatments for antibiotic-resistant infections.