Antibiotic Movement through Heterogeneous Biofilms

Abstract

Biofilms are communities of microorganisms that can form in the human microbiome and on medical implants among other locations. These communities provide greater protection for their member cells resulting in an increase in resistance to antibiotic treatment and persistent infections. There are several factors that may contribute to antibiotic resistance of biofilms. These studies were done concurrently with biological experiments to test the hypothesis that dense, rigid structures within the biofilm may be an additional mechanism for protection from antibiotics. A computational tool and workflow was developed to analyze bead movement for the characterization of biofilm biomaterial properties including rigidity. With this tool, the analysis revealed that the amyloid, curli, confers rigidity in biofilms, thereby restricting bead movement. Greater movement of the beads is seen in biofilms lacking curli and biofilms that produced complex heterogeneous rigid structures. A new model was also developed that uses microscopy imaging data to simulate diffusion-reaction of antibiotics within heterogeneous biofilms. This model was used to investigate the effect of the dense, rigid structures on antibiotic treatment through test simulations and simulations using biological imaging data. These studies reveal various properties about the dense, rigid structures that confer protection.