PhD defence

Illuminating Host Defence against Mycobacterial Infection: Interactions with Autophagy and LC3-Associated Phagocytosis

• S. Muñoz-Sánchez

Date

Tuesday 3 February 2026

Time

11:30 - 12:30 hour

Address

Academy Building
Rapenburg 73
2311 GJ Leiden

Supervisor(s)

• Prof. dr. A.H. Meijer
• dr. M. van der Vaart

Summary

Tuberculosis (TB) remains one of the world's deadliest infectious diseases. Although much progress has been made in understanding the causative agent Mycobacterium tuberculosis (Mtb), this pathogen is highly skilled at surviving inside the human body. It hides within immune cells, making it difficult to eliminate. This ability to evade the immune system contributes to persistent infection and ongoing transmission worldwide.

This thesis investigates how immune cells respond to mycobacterial infection during the earliest stages of the disease. To do this, a small tropical fish, the zebrafish, was used as a model organism. Zebrafish larvae are transparent, allowing researchers to observe infections in real time under the microscope. The fish were infected with Mycobacterium marinum, a close relative of Mtb, to study how immune cells attempt to control the infection.

The research focuses on autophagy, a process cells use to maintain balance and remove harmful invaders. By combining genetic and chemical tools with advanced 3D imaging, the study examined the roles of two proteins, PIKfyve and Rubicon. The results show that both proteins are essential for immune cells to properly process and degrade Mm. When these proteins do not function correctly, bacteria survive longer inside cells and replicate in higher numbers.

Overall, this work highlights new ways to support the body's own defences rather than directly targeting the pathogen. This approach, known as host-directed therapy, may help combat infections that are becoming increasingly resistant to antibiotics and contribute to the development of more sustainable treatments against mycobacterial infections.

PhD dissertations

Approximately one week after the defence, PhD dissertations by Leiden PhD students are available digitally through the Leiden Repository, that offers free access to these PhD dissertations. Please note that in some cases a dissertation may be under embargo temporarily and access to its full-text version will only be granted later.

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