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Researchers at UdeA School of Medicine’s Cellular Immunology and Immunogenetics Group (GICIG) managed to identify a gene responsible for resistance to tuberculosis treatments.
GICIG researchers, left to right: Diana Castaño, Blanca Ortiz, Cristian Alvarez, Gloria Vasquez, Andres Baena, Luis Barrera and Mauricio Rojas
Statistics released by the Secretary of Health of Antioquia revealed that existing tuberculosis treatments have proven ineffective in 40 percent of patients, and 12 percent of these cases is associated with bacteria resistant to drugs used to treat TB. These figures are causing alarm among Colombia’s TB prevention and control agencies.
The lack of new and effective TB treatments may be due to widespread ignorance of the ability of some strains of TB to escape protective host immune responses, which appears to be associated with specific functions of gene products of Mycobacterium tuberculosis that have gone unnoticed by the scientific community.
However, the gaps in TB research are narrowing as GICIG researchers have managed to identify new mechanisms of bacterial pathogenesis used by M. tuberculosis, particularly the PE_PGRS47 (Rv2741) gene.
The study’s lead author Andres Baena-Garcia, a professor at the UdeA School of Medicine and member of GICIG, says that autophagy (a ubiquitous cellular process that participates in the processing of antigens for MHC class II antigen presentation and in cells infected by vacuolar pathogens) has become a major subject of study in recent years among GICIG researchers.
Autophagy is the self-degradative process by which the cell rids itself of damaged organelles and proteins that accumulate in the cytoplasm which may affect cell metabolism. “We have found that the PE_PGRS47 gene has the ability to inhibit autophagy in macrophages and infected dendritic cells. Intracellular pathogens such as Mycobacterium tuberculosis reside in an isolated phagosome (a membrane-bound vesicle within the cell) to avoid being killed by the cell itself as it possesses genes which produce protein that somehow can inhibit defense mechanisms such as autophagy”, Professor Baena said.
This groundbreaking study to identify the gene responsible for inhibiting autophagy was conducted in collaboration with researchers from the Albert Einstein College of Medicine, one of the U.S. leading institutions for TB research.
The study is the first of its kind to observe the effects caused by the gene (especially bacterial replication and pathogenesis) in an in vivo animal model. The study was published in the August issue of Nature Microbiology, a prestigious British scientific journal dedicated to the publication of research in the biomedical sciences.
Although research results are conclusive further studies are needed to better understand the mechanisms by which M. tuberculosis is able to inhibit autophagy. “These mechanisms are key to the development of gene-based drugs to treat TB,” Professor Baena said.
Researchers from the Albert Einstein College of Medicine are currently working to develop PE_PGRS47 mutants in Bacillus Calmette-Guerin (BCG), a vaccine for tuberculosis that although is ineffective in preventing against pulmonary tuberculosis has shown to be effective against TB meningitis in children.
According to official reports released by the Regional Health Department and the Secretary of Health of Medellín the number of tuberculosis cases rose from 50 to 70 cases in 2016.
Risk factors include high chance to develop type II diabetes (which increases the risk to develop tuberculosis by 2 to 3 times), smoking prevalence and air pollution, which can lead to chronic obstructive pulmonary disease.