Charles E. Kaufman Foundation

2023 New Investigator Grant

Andrew Bridges, Ph.D.

Exploring the inter-species interactions controlling bacterial biofilm formation


Abstract

Bacteria exhibit remarkable social behaviors by collaborating with neighboring cells to perform group tasks. Among the collective behaviors that bacteria undertake is the formation of multicellular communities known as biofilms, in which resident bacteria attach to surfaces to survive as a group. Existing in biofilms provides advantages to cells, namely protection from environmental threats such as antimicrobial compounds, predation, and dislocation due to flow. A major goal of our work is to determine how bacteria make the decision to initiate or to exit from biofilm communities. Previously, we developed a novel automated microscopy approach to measure the biofilm lifecycle for the global pathogen and model organism Vibrio cholerae. We used this assay to determine that V. cholerae regulates its biofilm lifecycle transitions via cell-tocell signaling, a process that is thought to allow bacteria to measure the species composition of their local environment. To date, most mechanistic research, including our own, has focused on examining individual cell-to-cell signaling pathways at a time when bacteria are grown in simple laboratory culture conditions. The aim of this proposal is to determine how bacteria make lifestyle decisions in realistic conditions that approximate the environments in which they naturally grow, where nutrients and cell-to-cell signals are in flux and other organisms are present. To do so, we will utilize a multidisciplinary approach to uncover mechanisms, including high-content microscopy, which will allow us to examine diverse growth conditions, coupled with machine learning, biochemistry, genetics, and biophysics theory. The ideal outcome of this proposal is an understanding of how bacterial cell-to-cell signaling pathways function in complex communities to shape the living microbiomes in and around us. Down the road, we hope to exploit the signal integration components that we characterize to control bacterial behavior “on demand.”

Award amount: $150,000

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