For World Tuberculosis Day, 24 March 2026, we interviewed Dr Mariagrazia Di Luca, Head of Antimicrobial Resistance at ICGEB Trieste.
Why does tuberculosis persist, and why is it so difficult to treat? Despite decades of medical progress, tuberculosis (TB) remains one of the world’s deadliest infectious diseases. A key challenge lies in the bacterium itself. Mycobacterium tuberculosis is inherently slow-growing, which reduces the effectiveness of antibiotics that typically target actively replicating bacteria. Its thick, waxy cell wall further limits drug penetration, while its ability to hide in human cells allows it to evade treatment.
Treatment complexity adds another layer to the problem. Standard TB therapy can last up to six months, and patients often discontinue treatment early due to stigma, limited access to medicines, or severe side effects. This interruption does not cure the disease; instead, it promotes the survival and spread of antibiotic-resistant strains, making TB even harder to control.
Innovation at the Forefront: A New Approach to TB Treatment. The theme of World TB Day 2026 emphasises innovation, and researchers are responding with novel strategies. Among the most promising is the use of bacteriophages, viruses that specifically infect and kill bacteria. Unlike antibiotics, bacteriophages can evolve alongside bacteria, offering a dynamic, biological solution to drug resistance. This approach could be particularly valuable for treating resistant TB infections. However, progress has been slow due to technical challenges: working with Mycobacterium tuberculosis requires advanced biosafety level 3 (BSL-3) laboratories, which are costly and complex to maintain. Additionally, the bacterium’s slow growth means experiments can take weeks rather than days.
Despite these hurdles, researchers are committed to advancing phage-based therapies, recognising their potential to transform TB care.
Policy and Regulation: Enabling Innovation. Scientific breakthroughs must be matched by regulatory progress. Work is underway at the European level to integrate bacteriophage-based therapies into healthcare systems. As a member of the working group of the European Directorate for the Quality of Medicines & HealthCare, I am helping draft a chapter for the European Pharmacopoeia on an experimental drug based on bacteriophages, including guidelines on its inclusion in national regulatory frameworks. For the European Committee on Antimicrobial Susceptibility Testing, I am part of a subcommittee developing a phagogram to test the susceptibility of bacteria to bacteriophages. A diagnostic test is being developed to select phages to treat bacterial infections, which could be used alone or in combination with antibiotics to make current therapy more efficient.
Efforts include developing new pharmacopoeial standards and diagnostic tools that can identify which treatments, antibiotics, or bacteriophages are most effective for a given infection. Because bacteriophages are highly specific to individual bacterial strains, they represent a personalised medicine approach that does not always align with existing regulatory frameworks.
To unlock their full potential, policymakers must adapt regulations, raise awareness, and support the validation of personalized therapies for infectious diseases.
Strengthening Diagnosis and Primary Care Improving TB outcomes also depends on faster and more accessible diagnostics. Rapid, point-of-care testing is essential to detect TB early on and reduce community transmission. Equally important is the ability to quickly determine whether a strain is drug-resistant – an area where current tools remain limited.
Dhiraj Kumar, Group Leader of the Cellular Immunology lab at ICGEB New Delhi, comments: Efforts are underway to utilise the latest advances in whole-genome and targeted sequencing to precisely identify the drug resistance pattern at the time of diagnosis, which would immensely help to initiate an appropriate treatment regimen.
Looking ahead, advancing TB vaccine development to late-stage clinical trials and expanding research into bacteriophage therapies could significantly shorten or even replace long antibiotic regimens.
A Long Game Worth Playing. Both PIs agree that TB continues to challenge global health systems, with diagnostics, prevention, and treatment each needing significant improvement; while innovation offers renewed hope. From cutting-edge biological therapies and host-directed therapies to smarter diagnostics and adaptive policies such as nutritional supplementation, the fight against TB is entering a new phase.
As researchers push boundaries and rethink traditional approaches, one thing is clear: to outsmart TB, we must be as adaptable and persistent as the bacterium itself.
The Antimicrobial Resistance (AMR) Group, headed by Di Luca, investigates the molecular mechanisms underlying bacterial resistance and tolerance to antibiotics, as well as the development of new strategies to counteract these, such as phage therapy. Research focuses on human pathogenic bacteria, as listed by the World Health Organization as priority pathogens for the development of new antimicrobial approaches. The main objective is to understand how genetic and physiological factors contribute to antimicrobial resistance.
