Targeting hydrophobicity in biofilm-associated protein (Bap) as a novel antibiofilm strategy against Staphylococcus aureus biofilm.

In this study, a comprehensive in silico characterization was performed on Bap-family proteins to develop novel approaches to deal with Staphylococcus biofilms with a better understanding of the functional, structural, and topological features of Bap proteins. This study showed that Bap-like proteins in staphylococci are highly acidic, large, and cell-wall anchored proteins with tandem repeats. Structurally, Bap-family proteins have two distinct parts. N terminal part, which contains at least 2-3 calcium-binding EF-hand motifs that play a regulatory role in Bap functioning. Whereas the C-terminal part which predominantly consists of tandem repeats (TR), plays a functional as well as structural role. Bioinformatic analysis of Bap proteins and other homologous proteins revealed the presence of an amyloidogenic heptapeptide (STVTVTF) in the hydrophobic core of TRs of protein, responsible for the protein-protein interactions. The synthetic heptapeptide was tested if the masking effect on surface proteins could inhibit the S. aureus biofilm development and act as an 'antibiofilm-peptide'. The results clearly showed that the heptapeptide was able to inhibit early adhesion as well as biofilm development in the S. aureus biofilms. This approach has a promising potential to treat persistent biofilm-based S. aureus infections where Bap-like proteins do play a significant role.