These slow growing bacteria have long puzzled TB researchers with their fairly rapid resistance to antibiotics. Researchers may have been barking up the wrong tree in exploring genetics, because the answer seems to lie in the epigenetic domain.
Now, TB researchers at San Diego State University have uncovered a crucial clue to the mystery: the answer may lie in the epigenetic domain rather than the genetic domain where most scientists have concentrated their efforts.
Their discovery could help advance new diagnostics, therapeutics and vaccine targets.
Epigenetics is the study of inheritable changes in gene expression that do not involve a corresponding change to the underlying DNA sequence — meaning changes to the phenotype but no change in the genotype. This affects only the physical structure of the DNA, through a process called DNA methylation where a chemical ‘cap’ is added to the DNA molecule, preventing or facilitating the expression of certain genes.
The SDSU researchers describe the rapid response phenomenon they discovered as ‘intercellular mosaic methylation,’ a process by which Mycobacterium tuberculosis diversifies, creating multiple subpopulations each with its own phenotype. While antibiotics could kill many of these mutant subpopulations, at least a few do survive and develop drug resistance.
«We believe this also explains why diagnostic testing in some patients does not predict treatment failure, and why some patients come back months later with the disease reemerging in a far more resistant state,» said Faramarz Valafar, a TB expert with SDSU’s School of Public Health who studies the genetics and epigenetics of pulmonary diseases. «This is also why CT scans of the lungs of many «cured» patients show lesions with possible bacterial activity.»
Worldwide, TB is among the top 10 causes of death. It killed 1.4 million people in 2019, and about 10 million people fall ill with it each year, according to the World Health Organization.
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Materials provided by San Diego State University. Original written by Padma Nagappan. Note: Content may be edited for style and length.