Vanillin Enhances the Efficacy of Isoniazid against Mycobacterium smegmatis In Vitr

According to the World Health Organization’s Global Tuberculosis Report 2023, Southeast Asia accounted for 46% of tuberculosis cases in 2022, with Indonesia ranking second after India. Although tuberculosis is treatable with antibiotics, such as isoniazid (INH), the development of antibiotic resistance by Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis, can lead to treatment failure. Therefore, INH was combined with vanillin, an active natural compound, in an attempt to combat this resistance and tested against Mycobacterium smegmatis as a surrogate for MTB. Antibacterial activity was assessed by single-compound microdilution, followed by combination testing through the checkerboard microdilution and isobologram analysis. The minimum inhibitory concentrations for INH and vanillin were determined to be 9.14 μg/mL and 1610 μg/mL, respectively. Combination testing indicated an additive effect, with fractional inhibitory concentration indices and isobologram values showing a dose reduction index of 1.00 for INH and 255.56 for vanillin. These results suggest that vanillin may effectively inhibit M. smegmatis, but further studies should investigate vanillin’s potential in combination with other anti-TB agents resistant to MTB.