Related Experiment Video
Updated: Aug 11, 2025
09:34
An Automated Culture System for Use in Preclinical Testing of Host-Directed Therapies for Tuberculosis
Published on: August 16, 2021
1.9K
Gaucher disease protects against tuberculosis
Jingwen Fan1,2, Victoria L Hale2, Lindsey T Lelieveld3
1Molecular Immunity Unit, Cambridge Institute of Therapeutic Immunology and Infectious Diseases, Department of Medicine, University of Cambridge, Cambridge CB2 0QH, UK.
Summary
The Gaucher disease mutation GBA1 N370S enhances tuberculosis resistance in zebrafish by increasing microbicidal activity. This explains its prevalence in Ashkenazi Jews, as heterozygotes are susceptible, but homozygotes gain protection.
Area of Science:
- Genetics
- Immunology
- Microbiology
Background:
- Gaucher disease results from GBA1 gene mutations, causing lysosomal storage. This disease and related lysosomal disorders are prevalent in Ashkenazi Jews.
- A proposed hypothesis suggests GBA1 mutations offer a selective advantage, specifically protection against tuberculosis.
Purpose of the Study:
- To investigate the protective mechanism of the GBA1 N370S mutation against tuberculosis using a zebrafish model.
- To explore the role of glucosylsphingosine in macrophage lysosomes in conferring resistance.
Main Methods:
- Utilized a zebrafish model of Gaucher disease.
- Analyzed the impact of the GBA1 N370S mutation on tuberculosis resistance.
- Examined the microbicidal activity of glucosylsphingosine in macrophage lysosomes.
Main Results:
- The GBA1 N370S mutation significantly increased resistance to tuberculosis in the zebrafish model.
- Glucosylsphingosine within macrophage lysosomes demonstrated microbicidal activity against tuberculosis.
- Heterozygotes for the mutation remained susceptible to tuberculosis, unlike homozygotes.
Conclusions:
- The study reveals a mechanistic basis for tuberculosis protection conferred by the GBA1 N370S mutation.
- The findings provide biological plausibility for the selection of GBA1 N370S due to protection against tuberculosis, a historical major cause of mortality.
Related Concept Videos
01:29Pulmonary Tuberculosis I
297
Tuberculosis, often called TB, is a contagious illness primarily caused by Mycobacterium tuberculosis. It mainly affects the lung parenchyma but can also impact other body parts.
Causative Organism
The primary infectious agent causing tuberculosis is Mycobacterium tuberculosis, a slow-growing, acid-fast, aerobic rod that exhibits sensitivity to heat and ultraviolet light. Instances of Mycobacterium bovis and Mycobacterium avium contributing to the development of TB infection are rare.
Mode of...
Causative Organism
The primary infectious agent causing tuberculosis is Mycobacterium tuberculosis, a slow-growing, acid-fast, aerobic rod that exhibits sensitivity to heat and ultraviolet light. Instances of Mycobacterium bovis and Mycobacterium avium contributing to the development of TB infection are rare.
Mode of...
297
01:28Pulmonary Tuberculosis V
224
Medical management of tuberculosis (TB) patients involves a comprehensive approach that includes diagnosis, treatment, and monitoring. The specific strategies can vary depending on the type of tuberculosis (latent or active), the patient's overall health status, and other considerations.
Latent tuberculosis infection occurs when TB bacteria are present in a person's body, but are not causing illness or symptoms. It is not contagious, and preventive treatment is crucial to avoid the...
Latent tuberculosis infection occurs when TB bacteria are present in a person's body, but are not causing illness or symptoms. It is not contagious, and preventive treatment is crucial to avoid the...
224
01:28Pulmonary Tuberculosis II
292
Tuberculosis, or TB, is a bacterial infectious disease caused by Mycobacterium tuberculosis. While its primary impact is on the lungs, leading to pulmonary tuberculosis, it can also affect various other organs, a condition referred to as extrapulmonary tuberculosis.
Here is a detailed explanation of its pathophysiology:
Transmission: The process begins when a person inhales droplet nuclei containing M. tuberculosis. These are typically released into the air when an individual with pulmonary or...
Here is a detailed explanation of its pathophysiology:
Transmission: The process begins when a person inhales droplet nuclei containing M. tuberculosis. These are typically released into the air when an individual with pulmonary or...
292
01:31Pulmonary Tuberculosis III
406
Tuberculosis (TB) is a contagious infection primarily affecting the lung parenchyma but which can also affect other body parts. TB can be classified based on disease development, presentation, and the affected anatomical site.
The first classification is based on the development of the disease, and it includes the following categories:
The first classification is based on the development of the disease, and it includes the following categories:
406
01:26Pulmonary Tuberculosis IV
186
Tuberculosis, more commonly referred to as TB, is an infectious disease stemming from Mycobacterium tuberculosis. While it primarily impacts the lungs, TB can also affect other body areas. Given its severity and global impact, timely and accurate diagnosis is crucial for controlling its spread and improving patient outcomes.
Several diagnostic approaches are used to detect TB. The conventional method is the Tuberculin Skin Test (TST), also known as the Mantoux test. However, this method has...
Several diagnostic approaches are used to detect TB. The conventional method is the Tuberculin Skin Test (TST), also known as the Mantoux test. However, this method has...
186
01:23Cystic Fibrosis: Pathogenesis
321
Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
321