A*STAR study reveals why long-term lung risks persist after tuberculosis treatment

SINGAPORE – Even after completing treatment for tuberculosis (TB), some patients may remain vulnerable to further lung infections. Scientists at A*STAR Infectious Diseases Labs (A*STAR IDL) have uncovered how structures formed in the lungs during TB infection, known as tuberculous granulomas, can create conditions that allow secondary lung infections to take hold.

Published in Nature Communications, the study challenges the common assumption that successful TB treatment marks the end of long-term health risk. The findings provide new insight into why some individuals remain susceptible to further lung infections following TB, underscoring the importance of long-term lung health and appropriate follow-up care after treatment.

Understanding the link between TB and secondary infections

Tuberculosis continues to pose a public health concern in Singapore, with 1,156 new cases reported in 2024 (Ministry of Health, Singapore). Previous research[1] has shown that TB can lead to lasting changes in the lungs that may increase susceptibility to subsequent infections, including non-tuberculous mycobacterial (NTM) infections.

Infections caused by NTM, such as Mycobacterium abscessus, have been surpassing TB diagnoses in Singapore and many other countries for decades. A puzzling feature of this trend is that a significant proportion of NTM patients also have a current or recent history of TB. Clinical studies in Singapore have reported that around one-third of patients with NTM infections have a prior history of TB, suggesting that previous TB infection may increase vulnerability to subsequent lung disease.

The A*STAR IDL study provides a biological explanation for this link. The researchers found that TB granulomas, which can be detected through X-ray screening, can act as a protective niche for secondary bacteria, shielding them from immune defences and antibiotic treatment.

How bacteria survive inside TB granulomas

The study demonstrated that M. abscessus rapidly colonises pre-existing TB granulomas. Once inside these structures, the bacteria are protected from the immune system and are less susceptible to antibiotics. In contrast, bacteria located outside granulomas were quickly contained and eliminated.

Further work revealed how M. abscessus adapts to this hostile environment by feeding on necrotic material found at the centre of granulomas. Once established, the secondary infection was able to grow more rapidly than the original TB infection.

These findings suggest that clearing TB infection alone may not always be sufficient if granulomas persist and the lung does not heal fully.

Implications for long-term lung health

Senior author Dr Stefan Oehlers, Principal Investigator at A*STAR IDL, said the findings highlight an under-recognised aspect of TB recovery. “These findings identify an underappreciated role for TB granulomas in increasing susceptibility to other lung infections. TB treatment already requires months of antibiotics, and it is devastating for patients to then develop a secondary infection that can require additional years of treatment. Our work at A*STAR IDL shows that early and effective treatment of TB granulomas reduces the ability of Mycobacterium abscessus to grow, highlighting the importance of prevention, early intervention and appropriate follow-up care,” he said.

Dr Caroline Choong, Clinical Director for National Tuberculosis Care Centre at Tan Tock Seng Hospital, said the study reinforces the importance of looking beyond treatment completion. “Completing TB treatment does not always mean the lungs return to normal – many patients are left with residual scarring and damage. This study highlights the need for careful follow-up and monitoring after TB treatment, particularly for patients who may remain vulnerable to further lung infections.”

The study underscores the need for continued research into long-term lung health following TB infection, where recovery may extend beyond completion of treatment. By strengthening understanding of post-TB risks and recovery, the findings may help inform future research and approaches to monitoring lung health and longer-term health outcomes for Singapore.

Study citation: Wee, D., Pandey, M., Chen, Y. et al. Primary tuberculous mycobacterial granulomas provide a niche for superinfecting Mycobacterium abscessus. Nat Commun 16, 10760 (2025). https://doi.org/10.1038/s41467-025-65797-7

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About A*STAR Infectious Diseases Labs (A*STAR IDL)

A*STAR Infectious Diseases Labs (A*STAR IDL) was established in April 2021 with a mission to be a leading research institute of infectious diseases in antimicrobial resistance, respiratory and vector-borne diseases. A*STAR IDL brings together infectious diseases expertise from across multiple disciplines to drive cutting edge translational infectious diseases research to contribute to Singapore’s national preparedness and defence against the threat of emerging infections. Building upon a robust foundation of our strong biomedical research capabilities and complemented by our globally connected scientific network, A*STAR IDL aims to focus on innovative technologies in infectious disease detection, intervention and prevention with a pathway to impact on health and economic outcomes. https://www.a-star.edu.sg/idlabs

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About the Agency for Science, Technology and Research (A*STAR)

The Agency for Science, Technology and Research (A*STAR) is Singapore's lead public sector R&D agency. Through open innovation, we collaborate with our partners in both the public and private sectors to benefit the economy and society. As a Science and Technology Organisation, A*STAR bridges the gap between academia and industry. Our research creates economic growth and jobs for Singapore, and enhances lives by improving societal outcomes in healthcare, urban living, and sustainability. A*STAR plays a key role in nurturing scientific talent and leaders for the wider research community and industry. A*STAR’s R&D activities span biomedical sciences to physical sciences and engineering, with research entities primarily located in Biopolis and Fusionopolis. For ongoing news, visit www.a-star.edu.sg.

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[1] G J Fox, V N Nguyen, N S Dinh, L P H Nghiem, T N A Le, T A Nguyen, B H Nguyen, H D Nguyen, N B Tran, T L Nguyen, T N Le, V H Nguyen, T L Phan, K C Nguyen, J Ho, D C Pham, W J Britton, J R B M Bestrashniy, G B Marks, Post-treatment Mortality Among Patients With Tuberculosis: A Prospective Cohort Study of 10 964 Patients in Vietnam, Clinical Infectious Diseases, Volume 68, Issue 8, 15 April 2019, Pages 1359–1366, https://doi.org/10.1093/cid/ciy665