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.聽Salmonella聽alone is responsible for approximately 93.8 million illnesses and 155,000 deaths annually. Combined with the emergence of antibiotic-resistant聽Salmonella聽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 捆绑SM社区鈥檚 Faculty of Medicine in Montreal and Dr. Ivan Dikic, Director of the Institute of Biochemistry II at聽Goethe University Frankfurt. The results of their initial work were recently published in the journal聽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聽Salmonella聽infection. Through their work they were able to uncover an important gene, named CYRI, which is involved in聽Salmonella聽infections but also in other intracellular bacteria including聽Listeria聽(food poisoning) and聽Mycobacteria聽(tuberculosis).
Interestingly, they found that CYRI plays an important role in regulating bacterial entry into cells and bacterial dissemination in the body. 鈥淲hen mice carry a mutant form of CYRI, they become susceptible to infection,鈥� explains Dr. Malo. 鈥淭his study shows that CYRI plays a role in the complex host-pathogen interaction to privilege host clearance of the pathogen. We also showed that聽Salmonella聽in-turn try to reduce the levels of CYRI to its own advantage.聽 The result is a tug-of-war between the host and the pathogens for survival.鈥�
While the practical implications of the discovery remain unknown, the researchers believe that CYRI plays a role beyond fighting infections. 鈥淲e know that CYRI is important for embryo development and cell mobility,鈥� says Dr. Malo. 鈥淔uture work is required to further our understanding of the full nature of the role that CYRI plays in health and disease.鈥�
鈥淐YRI/FAM49B negatively regulates RAC1-driven cytoskeletal remodelling and protects against bacterial infection,鈥� by KE. Yuki, D. Malo, I. Dikic, et al, was published in聽Nature Microbiology聽on July 8, 2019. doi:聽10.1038/s41564-019-0484-8
This study was supported with funds from the Canadian Institutes of Health Research.聽
With files from the Institute of Biochemistry II, Goethe University, Frankfurt, Germany.