12:13am Sunday 08 December 2019

How Salmonella tackles cellular defense mechanisms

Researchers uncover new protein that plays key role in bacterial infections

Bacterial infections represent a major public health concern, accounting for over 300 million foodborne illnesses and 60% of related fatalities globally. Salmonella alone is responsible for approximately 93.8 million illnesses and 155,000 deaths annually. Combined with the emergence of antibiotic-resistant Salmonella strains, it is critical that researchers improve our understanding of the molecular details governing bacterial infections.

This need led to a collaboration between the labs of Dr. Danielle Malo, Professor in the Departments of Medicine and Human Genetics at McGill University’s Faculty of Medicine in Montreal and Dr. Ivan Dikic, Director of the Institute of Biochemistry II at Goethe University Frankfurt. The results of their initial work were recently published in the journal Nature Microbiology.

Using genetics and mouse model to make discovery

The researchers employed a multidisciplinary approach, known as forward genetics in mice in order to identify the genes that play a role in fighting Salmonella infection. Through their work they were able to uncover an important gene, named CYRI, which is involved in Salmonella infections but also in other intracellular bacteria including Listeria (food poisoning) and Mycobacteria (tuberculosis).

Interestingly, they found that CYRI plays an important role in regulating bacterial entry into cells and bacterial dissemination in the body. “When mice carry a mutant form of CYRI, they become susceptible to infection,” explains Dr. Malo. “This study shows that CYRI plays a role in the complex host-pathogen interaction to privilege host clearance of the pathogen. We also showed that Salmonella in-turn try to reduce the levels of CYRI to its own advantage.  The result is a tug-of-war between the host and the pathogens for survival.”

While the practical implications of the discovery remain unknown, the researchers believe that CYRI plays a role beyond fighting infections. “We know that CYRI is important for embryo development and cell mobility,” says Dr. Malo. “Future work is required to further our understanding of the full nature of the role that CYRI plays in health and disease.”

“CYRI/FAM49B negatively regulates RAC1-driven cytoskeletal remodelling and protects against bacterial infection,” by KE. Yuki, D. Malo, I. Dikic, et al, was published in Nature Microbiology on July 8, 2019. doi: 10.1038/s41564-019-0484-8

This study was supported with funds from the Canadian Institutes of Health Research. 

With files from the Institute of Biochemistry II, Goethe University, Frankfurt, Germany.

 

McGill University

 


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