Tuberculosis (TB)—an airborne mycobacterial infection—has been around for thousands of years and yet, in 2025, it remains as elusive as ever, making it one of the deadliest infectious diseases. It kills more than one million people every year globally and in India, two deaths occur every three minutes from TB, making it the country with the highest burden of TB in the world, according to the World Health Organization.

Significant challenges in treating TB hinder effective disease management and control. One of them is the lengthy treatment duration, typically spanning six to nine months, which can lead to patients discontinuing their medication prematurely, especially when they start feeling better after a few weeks. Incomplete treatment can result in the development of drug-resistant TB strains. Then there are side effects from TB medications such as nausea and fatigue that can cause patients to abandon treatment. And in many cases, when a person is infected with multidrug-resistant and extensively drug-resistant TB, it gets even more difficult to treat because they need the most effective first-line drugs that are given for longer and are often more toxic which can leave the patient physically and financially drained. Another challenge is that TB bacteria are able to enter a dormant state, rendering it less susceptible to conventional antibiotics.

There is no limit to the number of novel approaches that scientists have come up with and continue to develop to battle TB, as was clear at the Indo-Swiss Antimicrobial Resistance (AMR) Innovation Dialogue that took place in Switzerland, where 115 scientists, medical doctors, pharma executives, healthtech entrepreneurs and investors from Switzerland and India gathered to continue conversations that were started in October of 2023 in Bengaluru.

TB is one of the most complex AMR-related challenges, but AMR in general has dangerous implications for human life, including the possibility of death triggered by other bacterial infections. The last time a class of broad-spectrum antibiotics was developed was about five decades ago. Lack of awareness around AMR has prompted people to misuse antibiotics for infections that are not bacterial—particularly viral and fungal. The disease-causing bacteria in our bodies are developing resistance to the antibiotics and very soon we will run out of the strongest antibiotics available. At the same time, low- and middle-income countries struggle to get access to new life-saving antibiotics. This has serious consequences—when we genuinely need antibiotics to deal with medical issues like C-section deliveries, basic surgeries, pneumonia and tuberculosis, the antibiotics will be rendered useless and will not work on killing the disease-causing bacteria. And it takes years of research and trials to develop new antibiotics.

“If you give one drug to the bacterium, it will become resistant at some point. That’s nature”, said Prof. Michael Berney, Head of Division Pathogen Biology at the University of Zurich (UZH). One trick, he explained, is to give a cocktail of four antibiotic drugs (rifampin, isoniazid, pyrazinamide and ethambutol) in the correct dose over a period of six months to TB patients, which has proven to eradicate TB. This was in the 1960s. But we are in this situation now, Berney said, because patients would lower the dose if they couldn’t tolerate the side effects, or they would not take the medicines for the entire period prescribed, and obstacles like these made the bacteria that causes TB—Mycobacterium tuberculosis (M. tb) resistant to the drugs.

Right now, scientific interventions are not yet able to keep up with how quickly bacteria mutate and M. tb is a particularly difficult one to kill.

Dr. Glenn Dale, Chief Development Officer at the Swiss biotech company Bioversys spoke about Alpibactir (AlpE), a new drug combination developed to improve the treatment of TB and TB meningitis (TBM), which is a severe form of TB that affects the brain and spinal cord. In TB treatment, the antibiotic Ethionamide is used along with another anti-TB medication because it has to be activated inside the bacteria by an enzyme called EthA. But sometimes, M. tb develops resistance because it damages or shuts down this EthA activation step. If Ethionamide can’t be activated, it can’t kill the TB bacteria. Bioversys’ AlpE is a new drug that helps solve this problem. Instead of depending only on EthA, it makes the bacteria activate ethionamide through a different pathway. When scientists tested this combination, they found that AlpE made ethionamide much more powerful—even against tough, drug-resistant strains of TB that usually wouldn’t respond well.

Prof. Harinath Chakrapani, Professor of Chemistry at the Indian Institute of Science Education and Research (IISER) Pune is redesigning/modifying existing antibiotics into new forms that activate only once they’ve reached their bacterial target instead of inventing brand-new drugs, which can take more than decades. The bacteria would still be resistant, but targeted delivery would help against dormant TB bacteria which are less susceptible to antibiotics, and because it would only attack the bacteria in one location there wouldn’t be as many side effects for the patient. M. tb can go into a dormant state where they don’t grow—and when they’re dormant, non-modified antibiotics don’t work well. Moxifloxacin is an antibiotic that works well when TB bacteria are actively growing, but it struggles to kill the dormant ones. Prof. Chakrapani and his team developed a prodrug version of moxifloxacin that can attack dormant bacteria and kill them faster, potentially helping shorten TB treatment times.

Complementing this chemical strategy, Prof. Varadharajan Sundaramurthy, Associate Professor at the National Centre for Biological Sciences (NCBS), investigates TB’s behavior within the host. He notes that M. tb doesn’t behave like a uniform, easily targeted pathogen. Once it infects the body, it adapts in complex ways, especially by hiding. In hiding, some bacteria remain active, while others slow down, entering a dormant, drug-tolerant state, and this is part of what makes M. tb such a successful and deadly pathogen.

In fact, one of the newest drugs—bedaquiline—was seen as a breakthrough for treating multidrug-resistant TB, but resistance to it is already being seen in places like South Africa, Mozambique and India. Dr. Gunar Günther, Consultant Pulmonologist Pulmonology and Allergology at University Hospital Bern said we’re repeating the same mistakes of the past. In earlier decades, TB drugs were introduced and widely used without proper systems in place to monitor whether the bacteria were developing resistance, because of which we eventually lost the effectiveness of those treatments. The same thing is happening again, he said, adding that if we don’t test for drug resistance at both the individual and population level, we will quickly lose our best new medicines.

So where do we go from here?

If there was one aspect that everyone at the AMR Dialogue agreed on, it was speed. Diagnosing and treating fast.

Dr. Tavpritesh Sethi, Associate Professor of Computational Biology at the Indraprastha Institute of Information Technology, Delhi (IIIT Delhi) argued that timely diagnostics are what shift clinical decision-making. Without speed, even the most accurate test risks becoming irrelevant. He pointed out that predictive AI-integrated systems like AMRSense, which pull together clinical, genomic and epidemiological data to predict drug resistance before it spreads, could be beneficial.

And there is already progress being made in this regard. For instance, Dr. Daniel Richards, Postdoctoral Researcher at the Department of Chemistry and Applied Biosciences at ETH Zurich, is part of a team that is developing tools to detect TB and its drug resistance markers in under two hours. Along with his team, Prof. Adrian Egli, Director of the Institute of Medical Microbiology at UZH, has developed a real-time genomic surveillance platform, the Swiss Pathogen Surveillance Platform (SPSP), which allows clinicians and public health officials to identify resistance trends as they emerge.

But microbial resistance towards drugs that are supposed to kill them is only one part of this bigger public health crisis. While scientific approaches keep evolving, a concerted effort needs to be made in non-scientific endeavours as well. And one of the biggest challenges here is behavioural resistance. Not just in terms of TB, but generally in how bacterial infections are treated and how antibiotics are used.

Dr. Josianne Kollmann, Postdoctoral Researcher at the Department of Environmental Social Sciences at the Swiss Federal Institute of Aquatic Science and Technology (Eawag) who has spent years studying patient behaviour, argued that tackling AMR is not solely a scientific or medical challenge but a behavioural one. She talked about health psychology’s powerful methods for identifying the root causes of problematic behaviours and for designing interventions that encourage healthier, more responsible antibiotic use across populations.

AMR has a storytelling problem, Dr. Suzanne Suggs, who works in behaviour change communication at the University of Lugano, said at the Dialogue. It isn’t just the overuse and misuse of antibiotics in healthcare and farming, but also poor hygiene, sanitation, lack of diagnostics and broader socio-economic issues. An innovative behavioural approach, she recommended, was the Fleming Initiative, which combines behaviour change, public management, research and policymaking to bring together perspectives from multiple disciplines.

Ultimately, addressing TB will require not only scientific breakthroughs but also swift action, smarter systems and collective responsibility. Without addressing both microbial and human resistance, even the most promising advances risk slipping through our fingers.