Can we target tuberculosis bacteria by attacking their key enzymes? Recent research has revealed a family of lipases (enzymes that break down fats) in Mycobacterium tuberculosis (Mtb), the bacteria responsible for TB. These enzymes are suspected to play a crucial role in the bacteria’s survival by helping manage the bacteria’s cell structure or by degrading the host’s lipids (fats). Understanding their role could open the door to novel treatment strategies for TB.

Research goal

The main goal of this project is to understand the molecular functions of these putative Mtb lipases and assess whether they can be targeted with new antibiotics to fight TB. By developing specialised assays, the project aims to study how these enzymes interact with different lipid molecules and how inhibiting these lipases affects the bacteria’s ability to grow and survive, especially within human cells.

Interdisciplinary approach

This project is a collaborative effort between the Leiden Institute of Chemistry (LIC) and the Mycobacterial Research group of Leiden University Medical Center (LUMC), drawing on the expertise of biochemists, microbiologists, and infectious disease specialists. The combined knowledge and tools from these disciplines will enable a comprehensive investigation into how Mtb uses lipases to thrive in the human body and whether targeting these enzymes could provide a new way to fight TB.

Project description: Unveiling the role of Mycobacterium tuberculosis lipases in lipid metabolism and bacterial viability

Tuberculosis (TB) remains one of the deadliest infectious diseases, making the need for new treatments urgent. In this project, we focus on a specific family of enzymes, called lipases, found on the surface of Mycobacterium tuberculosis (Mtb), the bacterium that causes TB. We believe these enzymes could be crucial for the bacterium’s survival by helping it manage its outer layer or break down lipids (fats) from the host’s cells.

Our goal is to better understand how these lipases work and explore whether they can be targeted to fight TB. We will develop tests to examine which types of lipids these enzymes interact with and study the impact of blocking these enzymes on the survival of Mtb in laboratory models, including growing bacteria in the lab and testing the bacteria inside immune cells. The results of this research could provide the first step toward developing new treatments that target these lipases, potentially leading to innovative drug development for TB and similar infections.

• kiem grant
• mycobacterium tuberculosis
• tuberculosis

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