New Studies in the Fight Against Tuberculosis
08.08.2025
The genetic information of every cell is contained in its DNA. Back in 1953, Watson and Crick demonstrated that DNA takes on a double-helix structure. Numerous studies since then have shown that DNA is much more dynamic than initially believed, capable of adopting alternative (non-canonical) conformations beyond the classic double helix. One such configuration is the four-stranded fold known as the G-quadruplex.
A research team from the University of Padua — led by Sara Richter from the Department of Molecular Medicine and Roberta Provvedi from the Department of Biology, with Ilaria Maurizio, Emanuela Ruggiero, and Irene Zanin as co–first authors — has revealed for the first time the presence and role of G-quadruplex structures in the genome of Mycobacterium tuberculosis, the bacterium responsible for tuberculosis. Their study, titled “CUT&Tag Reveals Unconventional G-Quadruplex Landscape in Mycobacterium tuberculosis in Response to Oxidative Stress”, was published in Nature Communications.
As mentioned, G-quadruplexes are specific DNA structures that form in guanine-rich regions (guanine being one of the four DNA bases). These structures have been widely studied in eukaryotic organisms, such as humans, but had remained largely unexplored in the bacterial world.
The main distinction between eukaryotic cells (eukaryotes) and bacterial cells (prokaryotes) lies in the presence or absence of a well-defined nucleus and membrane-bound organelles. Bacteria, being prokaryotes, lack both, whereas eukaryotes have them.
Using an innovative technique known as CUT&Tag, the researchers mapped — for the first time — the presence of G-quadruplexes in the genome of Mycobacterium tuberculosis, finding that these structures form primarily within coding genes, in contrast to what is typically observed in eukaryotes.
"This study opens new perspectives for understanding gene regulation and stress response mechanisms in Mycobacterium tuberculosis, a globally significant pathogen," says Sara Richter of the Department of Molecular Medicine. "G-quadruplexes represent potential novel therapeutic targets for the development of new approaches to effectively fight tuberculosis."
One of the most significant aspects of the study is its focus on oxidative stress — a condition in which excessive free radicals are produced (often triggering inflammation), and the body's antioxidant defenses are overwhelmed. The researchers observed that oxidative stress conditions — similar to those encountered by the bacterium inside macrophages during infection — promote the formation of a greater number of G-quadruplexes.
Furthermore, the genes that exhibit these structures under stress conditions showed reduced gene expression, suggesting a potential role for G-quadruplexes in the bacterial stress response and survival. This positions them as promising targets for future therapeutic interventions.
