RESEARCH: BIOFILM
FOLDING PROJECT #12434 PROFILE

Bacteria often form protective communities called biofilms. A protein called LapD stops another protein (LapG) from breaking down a biofilm-building molecule. Scientists designed mini-proteins that mimic LapD to disrupt biofilm formation. They're using computer simulations to understand how these mini-proteins work and how to make them even better at stopping biofilms.

Note: This TLDR is a simplication and may not be 100% accurate.

Biofilms are aggregations of bacteria that occur in response to external stresses.

They are found in natural, industrial, and clinical environments, where they can be an impediment to effective antibiotic treatments.

In Pseudomonas fluorescens, this process is initiated by the Lap system, particularly the LapA adhesin.

LapG, a periplasmic protease, cleaves the N-terminus of LapA, releasing it from its adherent surface and inhibiting the ability to form a biofilm.

LapG’s ability to cleave LapA is prevented by LapD, which keeps the protease away from the cell surface through a unique protein-protein interaction (PPI) interface involving a highly conserved tryptophan of LapD. In an effort to develop molecules that can disrupt biofilm formation, the Bahl lab at the Institute for Protein Innovation has de novo designed high-affinity mini-proteins that mimic LapD and bind LapG.

In this collaborative project, the Voelz lab is using ab initio binding simulations of these mini-proteins to understand the binding mechanism, and investigate how sequence variability influences the binding reaction.

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Biofilms

Structured communities of bacteria encased in a self-produced matrix.

Biofilms are groups of bacteria that stick together and form a protective layer. They can be found everywhere, from your teeth to industrial pipes. Biofilms make it harder for antibiotics to work because the bacteria inside are protected by the matrix.

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Pseudomonas fluorescens

A common type of bacterium found in soil and water.

Pseudomonas fluorescens is a type of bacteria often found in the environment. Some strains can be helpful, while others can cause infections. This bacterium plays a role in the formation of biofilms.

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Lap system

A group of proteins involved in biofilm formation in Pseudomonas fluorescens.

The Lap system is a set of proteins that bacteria use to build their protective communities called biofilms. In Pseudomonas fluorescens, the Lap system helps create the structure and strength of the biofilm.

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LapA

An adhesin protein involved in biofilm formation.

LapA is a protein that helps bacteria stick together to build biofilms. It's like the glue that holds the biofilm structure together.

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LapG

A protease enzyme that cleaves LapA.

LapG is an enzyme that cuts apart LapA. This cutting action can prevent the formation of a strong biofilm.

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LapD

A protein that inhibits LapG activity.

LapD is a protein that stops LapG from working. It does this by keeping the two proteins apart so they can't interact.

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PPI

Protein-protein interaction.

PPI stands for protein-protein interaction. It describes how proteins interact with each other to carry out their functions.

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Mini-proteins

Small, engineered proteins with specific functions.

Mini-proteins are tiny versions of proteins designed to do a particular job. Scientists can create these mini-proteins to target specific molecules or processes.

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Ab initio binding simulations

Computer simulations of protein-protein interactions.

Ab initio binding simulations use computers to predict how proteins will interact with each other. This helps researchers understand how molecules bind and function.