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

Key Points

• The aim is to develop effective antimicrobial peptides targeting MRSA persisters using a mechanistic AI approach.
• Development of CAMPER framework combining machine learning and biophysical ranking.
• Identification of WP-CAMPER1 peptide through screening and testing.
• Evaluation of WP-CAMPER1's effectiveness in murine skin and biofilm infection models.
• Single-cell analysis to assess impact on S. aureus persisters.
• WP-CAMPER1 reduces S. aureus MW2 burden by 2.5 log₁₀ in prophylactic models.
• The D-enantiomer, WP-CAMPER1-d, reduces biofilm infection by 1.37 log₁₀.
• WP-CAMPER1-d decreases stationary-phase S. aureus MW2 persisters by 1.6 log₁₀ in infection models.