Validated In Silico Model for Biofilm Formation in Escherichia coli

Using Escherichia coli as the representative
biofilm former, we report here the development of an in silico model
built by simulating events that transform a free-living bacterial
entity into self-encased multicellular biofilms. Published literature
on ∼300 genes associated with pathways involved in biofilm
formation was curated, static maps were created, and suitably interconnected
with their respective metabolites using ordinary differential equations.
Precise interplay of genetic networks that regulate the transitory
switching of bacterial growth pattern in response to environmental
changes and the resultant multicomponent synthesis of the extracellular
matrix were appropriately represented. Subsequently, the in silico
model was analyzed by simulating time-dependent changes in the concentration
of components by using the R and python environment. The model was
validated by simulating and verifying the impact of key gene knockouts
(KOs) and systematic knockdowns on biofilm formation, thus ensuring
the outcomes were comparable with the reported literature. Similarly,
specific gene KOs in laboratory and pathogenic E. coli were constructed and assessed. MiaA, YdeO, and YgiV were found to
be crucial in biofilm development. Furthermore, qRT-PCR confirmed
the elevation of expression in biofilm-forming clinical isolates.
Findings reported in this study offer opportunities for identifying
biofilm inhibitors with applications in multiple industries. The application
of this model can be extended to the health care sector specifically
to develop novel adjunct therapies that prevent biofilms in medical
implants and reduce emergence of biofilm-associated resistant polymicrobial-chronic
infections. The in silico framework reported here is open source and
accessible for further enhancements.