First-in-class matrix anti-assembly peptide prevents staphylococcal biofilm in vitro and in vivo

Staphylococci are pathogenic biofilm-forming bacteria, source of multidrug-resistance and/or – tolerance causing a broad spectrum of infections. These bacteria are enclosed in a matrix that allows them to colonize medical devices such as catheters and tissue, and which protects against antibiotics and immune systems. Advances in antibiofilm strategies for targeting this matrix are therefore extremely relevant. Plants are constantly attacked by a wide range of pathogens, and have protective factors such as peptides to defend themselves. These peptides are common components in Capsicum peppers (CP). Here, we describe the development of CP bioinspired peptide “capsicumicine”. We demonstrate that capsicumicine strongly prevents methicillin-resistant S. epidermidis biofilm via a new extracellular “matrix anti-assembly” mechanism of action. Catheters pre-coated with capsicumicine decreased S. aureus colonization leading to the attenuation of infection, decreasing mice systemic infection. Capsicumicine is the first-in-class non-antibiotic, carbohydrate-binding peptide. ### Competing Interest Statement R.G.V.B, S.C.B.G, A.R.Z, A.J.M and R.G. are co-authors of a patent register of capsicumicine. Application number WO2020/169709555A1 at European Patent Office. Specific aspect of manuscript covered in patent application: its aminoacid sequence and bioactivity.