Molecular Interplay of Brucellosis and Tuberculosis: Insights into Telomere Biology, Oxidative Stress, and Drug Resistance Mechanisms

Brucellosis and tuberculosis (TB) are chronic infectious diseases of international public health importance, with developing countries being most affected. The diagnosis of brucellosis and tuberculosis co-infection remains challenging because both diseases present with overlapping nonspecific clinical manifestations, such as prolonged fever, fatigue, and weight loss, and elicit similar cell-mediated immune and inflammatory responses, which can complicate differential diagnosis, particularly in endemic regions. Recently, it has been shown that chronic infections affect cell stress pathways such as oxidative stress and telomere function. The current literature review provides an overview of the relationship between brucellosis and TB at a molecular level, focusing on telomere biology, oxidative stress and the mechanisms of antimicrobial resistance. Due to chronic immune response in brucellosis and TB patients, an increase in reactive oxygen species (ROS) levels is observed, leading to DNA damage and subsequent telomere shortening and alteration of telomerase activity. These alterations might be responsible for immune senescence, weakened defense response and persistent infection. In addition, different methods of drug resistance have been discovered among brucellae and mycobacteria, such as mutation in target sites, efflux systems and intracellular persistence, making their eradication difficult. Finally, the potential role of telomere-related genes and biomarkers of oxidative stress in diagnosis and prognosis is also highlighted. Insights into these interrelated pathways would allow us to have a better understanding of host–pathogen interactions and hence offer a possible means of developing new strategies in the fight against co-infection by finding new biomarkers.