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<p>Developing short, stable, and potent antimicrobial peptides is a promising strategy to combat antibiotic resistance and persistence. We present CAMPER (<b>C</b>onstraint-driven <b>AMP E</b>ngineering with <b>R</b>anking), a mechanistic artificial intelligence framework that integrates machine learning with biophysical ranking to prioritize membrane-targeting peptides effective against persister and biofilm forms of methicillin-resistant <i>Staphylococcus aureus</i>. We apply CAMPER to identify WP-CAMPER1 (12mer) that kills <i>S. aureus</i> MW2 at a minimal inhibitory concentration of 4 µg/mL. A 2% topical WP-CAMPER1 formulation reduces <i>S. aureus</i> MW2 burden by 2.5 log<sub>10</sub> (<i>p</i> &lt; 0.0002) in a murine prophylactic skin infection model, while its D-enantiomer, WP-CAMPER1-d, achieves 1.37 log<sub>10</sub> (<i>p</i> &lt; 0.0001) reduction in an established biofilm infection model. Single-cell analysis using a high-throughput microfluidic system shows that WP-CAMPER1-d reduces exponential-phase persisters of <i>S. aureus</i> USA300, and, in a deep-seated murine thigh infection model, decreases stationary-phase <i>S. aureus</i> MW2 persisters by 1.6 log<sub>10</sub> (<i>p</i> &lt; 0.0001).</p>

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CAMPER: mechanistic artificial intelligence for designing peptides that target MRSA persisters

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月9日

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  • Fadi Shehadeh,
  • Biswajit Mishra,
  • Raquel Ferrer-Espada,
  • Anindya Basu,
  • LewisOscar Felix,
  • Charilaos Dellis,
  • Narchonai Ganesan,
  • Liyang Zhang,
  • Andrew T. Martens,
  • Youlian Goulev,
  • Michael B. Sherman,
  • Johan Paulsson,
  • Mandar T. Naik,
  • Paul P. Sotiriadis,
  • Eleftherios Mylonakis

摘要

Developing short, stable, and potent antimicrobial peptides is a promising strategy to combat antibiotic resistance and persistence. We present CAMPER (Constraint-driven AMP Engineering with Ranking), a mechanistic artificial intelligence framework that integrates machine learning with biophysical ranking to prioritize membrane-targeting peptides effective against persister and biofilm forms of methicillin-resistant Staphylococcus aureus. We apply CAMPER to identify WP-CAMPER1 (12mer) that kills S. aureus MW2 at a minimal inhibitory concentration of 4 µg/mL. A 2% topical WP-CAMPER1 formulation reduces S. aureus MW2 burden by 2.5 log10 (p < 0.0002) in a murine prophylactic skin infection model, while its D-enantiomer, WP-CAMPER1-d, achieves 1.37 log10 (p < 0.0001) reduction in an established biofilm infection model. Single-cell analysis using a high-throughput microfluidic system shows that WP-CAMPER1-d reduces exponential-phase persisters of S. aureus USA300, and, in a deep-seated murine thigh infection model, decreases stationary-phase S. aureus MW2 persisters by 1.6 log10 (p < 0.0001).