We are pleased to announce the Ph.D. Thesis Defense Seminar of Wenjie Zeng. This will take place on Friday, April 25th, 2025, 10:00AM in the G01 Biotechnology Building.

In case you cannot make it in person, please find the zoom link here, meeting ID: 924 3839 8966; Password: 609712

“Manipulation of Eukaryotic Cytoskeleton and Mitochondrion by Legionella pneumophila”

Legionella pneumophila is a Gram-negative, facultative intracellular pathogen of phagocytic
cells and the causative agent of Legionnaires’ disease. To facilitate its intracellular survival
and replication, Legionella secretes over 300 effector proteins that hijack and manipulate host
cell processes. Recent advances have identified several families of effectors that target two
critical eukaryotic structures: the cytoskeleton and mitochondria. However, the precise
mechanisms by which these structures are subverted remain largely unknown.

In this work, I identified a lysine fatty-acyltransferase effector, Lfat1, through
localization screening. Lfat1 modifies host small GTPases and contains a previously
uncharacterized actin-binding domain (ABD), which may serve as a novel alternative to
conventional F-actin probes. Additionally, using bioinformatic analyses, I discovered a
mitochondrial-localized effector, Lem12, which co-opts a conserved eukaryotic protein
phosphatase to dephosphorylate mitophagy activators, thereby suppressing this essential
mitochondrial quality control pathway.

Together, these discoveries provide new insights into how pathogens like Legionella
can manipulate fundamental cellular systems. These findings not only advance our
understanding of host-pathogen interactions but also contribute to the development of novel
tools and therapeutic strategies across fields such as cell biology, microbiology, and
immunology.

Publications:
1. Zeng, W., Komaniecki, G., Liu, J., Lin, H., and Mao, Y (Submitted, 2025) “Cryo-EM structure revealed a novel Factin binding motif in a Legionella pneumophila lysine fatty-acyltransferase.”
2. Zeng, W., Kang, J., Wan, M., Yu, H., and Mao, Y (Under preparation) “Legionella pneumophila effector Lem12 attenuates mitophagy by hijacking the conserved phosphatase PP1C.”
3. Illava, G., Jayne, R., Finke, A. D., Closs, D., Zeng, W., Milano, S. K., Huang, Q., Kriksunov, I., Sidorenko, P., Wise, F. W., Zipfel, W. R., Apker, B. A., & Thorne, R. E. (2021). “Integrated sample-handling and mounting system for fixed-target serial synchrotron crystallography.” Acta crystallographica. Section D, Structural biology, 77(Pt 5), 628–644. https://doi.org/10.1107/S2059798321001868