Overview

Problem

Microplastics in the environment are colonized by bacteria that form biofilms acting as vectors for pathogens and antibiotic-resistance genes, but the molecular features that drive bacterial adhesion to plastic surfaces are still not well understood.

Question

Which structural features make bacterial proteins stick to plastics, and can we use them to design peptides that block adhesion?

Hypothesis

Surface hydrophobicity, charge distribution and conserved adhesion motifs of three bacterial amyloid adhesins (CsgA, FapC and TasA) predict their binding to polyethylene, and these features can be used computationally to guide the rational design of anti-adhesion peptides.

Aims

Aim 1 (in silico) Computationally identify and characterize the residues that mediate adhesion of CsgA, FapC and TasA to polyethylene (PE) and polystirene (PS) through structure prediction (AlphaFold), surface analysis in PyMOL, polymer construction in AlphaFold3 and Boltz colab, protein–polymer docking in AlphaFold2 and affinity estimation with PRODIGY. Also, design three cassettes to be used in vitro assays.

Aim 2 (development)

Use the residue-level adhesion map from Aim 1 to design anti-adhesion peptides with PepMLM and moPPIt, validate the predicted peptide–adhesin complexes with AlphaFold 3 and PeptiVerse, and advance the most promising candidates to in vitro (and eventually in vivo) testing on PE and PS surfaces, using the cassettes.

Aim 3 (visionary)

Establish rational, residue-level control of microbial adhesion to synthetic polymers, extending the framework to additional clinically relevant biofilm proteins such as Bap from Staphylococcus aureus, with applications in medical devices, non-toxic antifouling coatings, enhanced bioremediation of microplastics, engineered living materials and diagnostic platforms.