Reverse zoonosis in bovine tuberculosis: The neglected threat of Mycobacterium tuberculosis infection in cattle

Tuberculosis (TB), caused by members of the Mycobacterium tuberculosis complex (MTBC), remains a significant global health concern. While zoonotic transmission of M. bovis from cattle to humans is well documented, reverse zoonotic transmission of M. tuberculosis from humans to cattle has received far less attention. This review provides the first comprehensive synthesis of M. tuberculosis infections in cattle, drawing on evidence from farms, households, and slaughterhouses where human-animal contact is most intense. Available data indicate that such spillover events are uncommon compared with M. bovis infection, and that infectious humans-via aerosols or sputum-contaminated feed or environments-represent the primary, and likely exclusive source of infection for cattle, as no sustained cattle-to-cattle transmission has been reported. Experimental M. tuberculosis infection in cattle consistently demonstrates an attenuated phenotype, with mild pathology and low bacterial loads. However, the identification of multidrug-resistant and pre-extensively drug-resistant M. tuberculosis strains in cattle raises a potential future concern regarding cross-species transmission, despite the fact that transmission back to humans has not been observed yet. Enhancing routine molecular diagnostics is vital for precise MTBC differentiation and a better grasp of cross-species transmission dynamics. A unified One Health strategy, which combines human, animal, and environmental monitoring, is essential to track and address this emerging threat.