Mechanisms of Mycobacterium tuberculosis disease and the impact of co-infections and post-TB complications

Background Mycobacterium tuberculosis (Mtb) remains a leading cause of global morbidity and mortality. Viral, bacterial, fungal, and parasitic co-infections substantially modify tuberculosis (TB) pathogenesis, and an increasingly recognised population of TB survivors develops post-TB lung disease (PTLD), which predisposes them to recurrent respiratory infections. Objectives To summarise current evidence on 1) Mtb pathophysiology and immunopathogenesis; 2) mechanisms by which major viral, bacterial, fungal, and parasitic co-infections alter TB progress; and 3) infectious complications associated with PTLD. Content Mtb exploits innate immune evasion, altered macrophage activation, and granuloma remodelling in order to persist. Viral co-infections, particularly HIV, influenza, and severe acute respiratory syndrome coronavirus 2, impair T-helper 1 immunity, disrupt cytokine signalling, increase bacterial load, and drive progression to severe or disseminated TB. Bacterial pathogens ( e.g. Streptococcus pneumoniae , Staphylococcus aureus , Klebsiella pneumoniae , Pseudomonas aeruginosa ) complicate diagnosis, increase severity, and contribute to antimicrobial resistance. Fungal and parasitic infections skew immunity and can delay diagnosis or reduce vaccine efficacy. PTLD results from sustained inflammation, matrix metalloproteinase activation, fibrosis, bronchiectasis, and cavitation; these structural changes favour chronic colonisation by opportunistic bacteria and long-term functional impairment. Conclusions TB pathogenesis is profoundly influenced by co-infections, and PTLD is an under-recognised driver of chronic respiratory morbidity. Integrated diagnostics, coordinated management of multimorbidity, and tailored strategies for PTLD are essential to reduce TB-related burden.