RESEARCH: BIOFILM
FOLDING PROJECT #18454 PROFILE

Bacteria can stick together in groups called biofilms, making them hard to treat with antibiotics. A project is using computer simulations to design tiny proteins that block a protein (LapG) involved in biofilm formation. These mini-proteins act like shields, preventing LapG from cutting another protein (LapA) needed for biofilm building. This research could lead to new ways to fight infections caused by 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

Communities of microorganisms that adhere to surfaces.

Biofilms are complex communities of bacteria or other microorganisms that stick together and to surfaces. They can form in various environments, including hospitals, industrial settings, and even our bodies. Biofilms often resist antibiotics and disinfectants, making them a significant challenge in healthcare and industry.

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Bacteria

Single-celled microorganisms.

Bacteria are microscopic organisms found everywhere on Earth. They play essential roles in ecosystems, breaking down organic matter and cycling nutrients. While some bacteria cause diseases, most are harmless or even beneficial to humans.

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Antibiotic

A medication that inhibits the growth of or kills bacteria.

Antibiotics are powerful medicines used to treat bacterial infections. They work by targeting specific processes essential for bacterial survival, such as cell wall synthesis or protein production.

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Lap System

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

The Lap system is a complex set of proteins found in Pseudomonas fluorescens bacteria that plays a crucial role in forming biofilms. These structures allow bacteria to attach to surfaces and protect themselves from environmental stresses.

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LapA

An adhesin protein involved in biofilm formation.

LapA is a crucial protein for biofilm formation in Pseudomonas fluorescens. It acts as an adhesin, allowing bacteria to attach to surfaces and each other.

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LapG

A protease that cleaves LapA.

LapG is an enzyme responsible for breaking down LapA, thereby preventing biofilm formation in Pseudomonas fluorescens. This regulation helps control the growth and structure of biofilms.

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LapD

A protein that inhibits LapG.

LapD plays a crucial role in regulating biofilm formation by preventing LapG from cleaving LapA. It achieves this through a specific protein-protein interaction.

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Mini-proteins

Small proteins with specific functions.

Mini-proteins are artificially designed proteins with reduced size and tailored functionalities. They hold promise for various applications, including drug development and biosensing.

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Ab Initio

Based on fundamental principles without experimental data.

Ab initio methods in computational science rely on theoretical principles to predict properties or behavior. This approach avoids relying on experimental input and can provide valuable insights into complex systems.