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Biofilm-forming bacteria are an important reservoir of nosocomial infections, and source of antibiotic resistance and tolerance. These bacteria are enclosed in a complex matrix that allows them to adhere to medical devices and tissue, and which also protects against antibiotics and immune systems. Advances in antibiofilm strategies for targeting the biofilm matrix are therefore extremely relevant in the fight against multidrug-resistant and/or -tolerant bacteria. 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 red pepper seeds, and here we investigate and identify a new antibiofilm peptide, “capsicumicine.” We demonstrate that capsicumicine prevents methicillin-resistant Staphylococcus epidermidis adhesion as well as biofilm establishment and maintenance via a new extracellular “matrix anti-assembly” (MAA) mechanism of action. In this manner, capsicumicine disturbs the construction of the matrix, and therefore its functioning. Importantly, the peptide is not an antibiotic and it is not cytotoxic, thus capsicumicine is an exciting new alternative treatment for prevention of biofilm infections. Significance Both pathogenic drug resistance and tolerance are favored by biofilm development. Indeed, biofilm-covered microorganisms display antibiotic resistance up to 1000 times higher than planktonic ones. Staphylococcus epidermidis is remarkably good at forming biofilm, and is therefore highly associated with medical device infection. Here, we report the discovery of “capsicumicine,” a novel antibiofilm peptide derived from Capsicum bacattum . This prevents the establishment of S. epidermidis biofilm via a new mechanism of action, matrix anti-assembly (MAA). MAA is not antibiotic, and is based on extracellular interactions that force bacteria to remain planktonic, letting immune systems and traditional antibiotics more easily clear the infection. For this reason, MAA should confer a lower susceptibility to bacterial resistance development. Very importantly, capsicumicine is not cytotoxic. |
