RESEARCH: BIOFILM
FOLDING PROJECT #18446 PROFILE

Bacteria can group together to form sticky biofilms, making them hard to treat with antibiotics. A project relates to a protein called LapD that stops another protein (LapG) from breaking down a key biofilm building block. Scientists are designing mini-proteins that act like LapD to disrupt biofilm formation and use computer simulations to understand how these mini-proteins work.

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 groups of bacteria or other microorganisms that stick together and create a protective layer around themselves. They can be found in many environments, including inside the human body. Biofilms can be difficult to treat because they are more resistant to antibiotics than individual bacteria.

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Bacteria

Single-celled organisms that lack a nucleus.

Bacteria are tiny living things that are found everywhere. Some bacteria are helpful, while others can cause disease. They reproduce quickly and can adapt to different environments.

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Antibiotic

A medicine that kills or inhibits the growth of bacteria.

Antibiotics are drugs that are used to treat bacterial infections. They work by killing or stopping the growth of bacteria. Antibiotics are very important for treating serious infections, but overuse can lead to antibiotic resistance.

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Pseudomonas fluorescens

A species of bacteria commonly found in soil and water.

Pseudomonas fluorescens is a type of bacteria that can be found in many places. Some strains are beneficial, while others can cause disease in plants and animals.

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Lap system

LapsA, LapG, and LapD proteins involved in biofilm formation.

The Lap system is a set of proteins that bacteria use to build biofilms. It involves three main proteins: LapA, which helps the bacteria stick together; LapG, which cuts LapA loose; and LapD, which prevents LapG from cutting LapA.

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LapA

Adhesin protein involved in biofilm formation.

LapA is a protein that helps bacteria stick to surfaces. It is part of the Lap system, which is used by bacteria to build biofilms.

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LapG

Periplasmic protease involved in biofilm formation.

LapG is a protein that cuts LapA loose. It is part of the Lap system, which is used by bacteria to build biofilms.

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LapD

Protein involved in inhibiting LapG activity.

LapD is a protein that prevents LapG from cutting LapA. It is part of the Lap system, which is used by bacteria to build biofilms.

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PPI

Protein-protein interaction.

A PPI is when two proteins interact with each other. This can happen in many ways, and it's important for a lot of biological processes.

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Mini-proteins

Small proteins designed for specific functions.

Mini-proteins are small versions of proteins that have been designed to do a specific job. They are being developed for many different applications, such as medicine and agriculture.

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Ab initio binding simulations

Computer simulations of protein binding interactions.

Ab initio binding simulations are computer programs that can predict how proteins will bind to each other. This can be used to design new drugs and understand how biological processes work.