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At the Indian Institute of Science (IISc), researchers have made significant strides in understanding how the tuberculosis (TB) bacterium endures within the human body for extended periods, shedding light on a crucial mechanism aiding its persistence.
Their study, published in Science Advances, identifies a single gene pivotal in facilitating the production of iron-sulphur clusters—essential components for the TB bacterium’s sustained existence.
Iron-sulphur clusters play a multifaceted role by aiding energy production through respiration and fortifying the bacterium to withstand the harsh lung environment, thereby promoting infection.
Mycobacterium tuberculosis (Mtb), the causative agent of TB, can remain latent within the body for decades without exhibiting symptoms. The bacterium’s ability to hide in oxygen-depleted lung pockets in a dormant state makes eradication challenging.
Mayashree Das, the study’s first author and a doctoral student at IISc’s Department of Microbiology and Cell Biology (MCB), highlights the bacterium’s tendency to evade immune detection and persist within a subset of the human population, potentially reactivating to cause infection.
Understanding this persistence is crucial for devising strategies to eradicate TB, as articulated by Amit Singh, Associate Professor at MCB and the study’s corresponding author.
The research team explored how Mtb generates iron-sulphur clusters, primarily orchestrated by the SUF operon—a cluster of genes. Intriguingly, they discovered a single gene, IscS, capable of independently producing these clusters, unveiling an alternative mechanism.
By examining Mtb lacking the IscS gene, the researchers observed heightened virulence and exacerbated disease progression in mice models compared to the chronic, persistent infection typical of TB patients. The absence of IscS led to unregulated activation of the SUF operon, amplifying Mtb’s virulence.
This understanding of the IscS gene’s role in controlling the SUF operon sheds light on TB persistence. Additionally, bacteria devoid of IscS displayed altered antibiotic sensitivity, paving the way for potential novel treatment avenues.
The researchers envision a combined approach of antibiotics and drugs targeting IscS and SUF as a promising strategy to combat TB more effectively, aiming to curtail the bacterium’s persistence and enhance treatment efficacy.
