Legionella pneumophila, the bacterium responsible for Legionnaires’ disease, employs a unique strategy to disrupt protein synthesis in host cells. One of its secreted proteins, SidI, functions as a transfer-RNA mimic, directly binding to and modifying the ribosome.

Through cryo-electron microscopy the structure of SidI was revealed, with its tRNA-like N-terminal domain and glycosyl transferase C-terminal domain.  SidI’s tRNA mimicry and enzymatic activity effectively block protein synthesis akin to the potent toxin ricin. The translational pauses induced by SidI trigger a stress response similar to ribosome collisions, activating stress kinases and leading to the accumulation of ATF3, a transcription factor promoting cell death.  This mechanism unveils how Legionella manipulates a ribosome-to-nuclear signaling pathway.  The study was carried out by Prof. Lan Wang from the Division of Life Science at HKUST and Dr. Advait Subramanian from Altos Labs Inc. in California.  Their research on SidI sheds light on the use of molecular mimicry by pathogens to hijack critical cellular processes, providing fundamental insights into host cell function and stress response pathways.

 

Journal Reference:

Subramanian, A., Wang, L., Moss, T. et al. A Legionella toxin exhibits tRNA mimicry and glycosyl transferase activity to target the translation machinery and trigger a ribotoxic stress response. Nat Cell Biol 25, 1600–1615 (2023). https://doi.org/10.1038/s41556-023-01248-z

Source: Phys.org News Dec 5 2023

 

 

 

 

One of our LIFS faculty members, Dr. Wang Lan, Assistant Professor of the Division of Life Science, received the Croucher Innovation Award, 2023.  Prof. SUN Dong, the Secretary for Innovation, Technology and Industry of the Hong Kong Special Administrative Region was the Guest of Honor at the ceremony.

Dr. Wang is interested in understanding the molecular mechanisms that determine the health of the mitochondria. Mitochondrial dysfunction underlies many human diseases. Additionally, Dr. Wang is also interested in discovering new mechanisms that regulate protein translation and how pathogens could exploit these mechanisms to manipulate the host cell for their own advantage.

Croucher Innovation Awards

Established in 2012, the Croucher Innovation Awards aim to identify a small number of exceptionally talented scientists working at an internationally competitive level and to offer substantial support to these “rising stars” at a formative stage in their careers. The scheme is designed to enable recipients to pursue their own scientific, intellectual and professional inclinations, to advance their expertise, to engage in bold new work, and to contribute to the development of education and research in Hong Kong. Each award carries a value of up to HK$5 million over five years.

Cyanophages, viruses that infect cyanobacteria, are abundant in the oceans and have a profound influence on cyanobacterial metabolism, evolution, and community dynamics. These viruses play a crucial role in global biogeochemical cycles by impacting host photosynthesis and carbon fixation. Among cyanophages, the T7-like podoviruses, including the recently discovered MPP-C clade, exhibit unique characteristics and infection kinetics. However, the lack of high-resolution structural information has hindered our understanding of their infection mechanisms.

Cyanobacteria are crucial for Earth’s ecosystems as they produce oxygen and serve as a food and fuel source. Infections by cyanophages can alter bacterial behavior, affecting their energy production from sunlight and causing significant carbon loss annually. Understanding the viruses’ mechanisms and their impact on bacteria, oceans, and climate is essential.

 

 

Moreover, insights into their infection processes can aid in the development of virus-based strategies to control harmful cyanobacteria in freshwater, benefiting agriculture and ensuring clean drinking water. The team’s findings were published in the journal Nature Communications, and future research aims to further explore the virus’s infection process and resolve unresolved parts of its structure relating to host recognition and infection.

These findings highlight the importance of VCAM1-APOE signaling in AD pathogenesis and propose VCAM1 as a promising target for therapeutic interventions. Prof. Nancy Ip expressed the significance of these discoveries in expanding our understanding of the disease and emphasized the need to identify appropriate drug targets for effective AD treatment. The research team aims to continue their innovative approaches in pursuit of this goal.