4 min readFeb 2, 2026 12:00 PM IST
First published on: Feb 2, 2026 at 12:00 PM IST
Studying tuberculosis (TB) in the lab has long meant relying on flat cell cultures that look nothing like the human lung. In a breakthrough approach, researchers at the Indian Institute of Science (IISc), Bengaluru, have built a three-dimensional model that better reflects how TB behaves inside the body. Using a soft collagen gel that mimics the texture and structure of lung tissue, the 3D model reveals disease features and drug responses that conventional lab systems often miss.
Cutting edge research is expected to arm India’s fight against TB as it still carries one of the world’s largest burdens (estimated to be around 2.5-3 million cases). The research is funded by India Alliance, a partnership between the Department of Biotechnology and Wellcome Trust, UK.
What’s the efficacy of the new model?
Infected human immune cells were injected into the model. Soon the researchers found that both the human cells and TB bacteria behaved much more like they do in real patients than in flat (2D) lab models. Key TB features such as fat-filled immune cells and clusters of TB bacteria also appeared in this model.
According to Dr Rachit Agarwal, a DBT/Wellcome Trust Intermediate Fellow at IISc, this model could demonstrate the effects of the TB drug Pyrazinamide, something that other lab models usually fail to show. “This new 3D system is a much more realistic way to study TB and test new medicines that could help speed up treatments,” he says.
This 3D hydrogel model is different from existing 2D infection models because it provides mechanical and biochemical cues to host cells and bacteria that are similar to those of the human lung micro environment. It is modular, scalable and can be easily adopted to study drug efficacy and infection biology for extended periods.
What are existing models to test drug efficacy?
At the most basic level, drug testing is performed directly on planktonic bacterial cultures. “Another popular model is to use mammalian cells cultured on two-dimensional plates. These mammalian cells are infected with bacteria and tested with the drugs. However, results from either of these models may not translate effectively into humans, as seen with Pyrazinamide. Alternatively, drug testing is routinely conducted on animal models, such as mice. But with the new FDA Modernisation Act 3.0 (USA) and the New Drugs and Clinical Trials Rules (India), three-dimensional organoids and organ-on-a-chip models are advocated as reliable substitutes for testing safety and efficacy of drugs before human trials,” Dr Agarwal explains.
Is it possible to test and identify drugs that work against DR and XDR bacteria?
Given the ease of making these hydrogels and their similarity to human tissue, it is possible to conduct reliable drug efficacy testing. “While so far, we have not carried out drug resistant bacteria studies in this model, by infecting mammalian cells in our hydrogels with drug-resistant clinical bacterial isolates, it should be possible to test and identify drugs that work against drug-resistant (DR) and XDR (extensively drug-resistant) bacteria,” he says.
A hotspot for drug-resistant TB, India has been one of the major contributors to the global MDR (multi drug-resistant)/RR-TB (Rifampicin-Resistant TB) in 2024. Rifampicin is a first line broad-spectrum antibiotic.
Dr Agarwal says that researchers are building on this model to further mimic tuberculosis granulomas – tight aggregates of immune cells surrounding the bacteria, a pathological hallmark of TB. “These tight structures in the lung have varying disease outcomes, ranging from bacterial clearance to containment to bacterial outgrowth and can also pose challenges for drug delivery to the core. Such a model could be of immense importance to the field in understanding host-pathogen interactions and drug efficacies,” he adds.
IISc researchers have developed a 3D lung model that mirrors real human tissue, revealing TB behaviour and drug responses missed by conventional lab systems. (File Photo) 
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