Identification of Probiotic Strains with Anti-Tuberculosis Activity and Their Characterization as Potential Therapeutic Agents

초록

Tuberculosis (TB) remains a global health crisis, with the emergence of multidrugresistantstrains necessitating the development of novel therapeutic strategies. Approximately one-fourth of the world’s population, or 2 billion people, are infectedwith latent TB. The rise of multidrug-resistant (MDR), extensively drug-resistant(XDR), and totally drug-resistant (TDR) strains of Mycobacterium tuberculosis (M. tb) poses a significant threat, reducing the effectiveness of conventional treatments. The limitations of current antibiotic regimens underscore the urgent needfor alternative approaches. This highlights the urgent need for new anti-tuberculosisdrugs. Probiotics, known for their health benefits against various infections, mayoffer a promising alternative in combating antibiotic-resistant TB. This studyaimed to identify novel probiotic strains with anti-tuberculosis potential. Sevenprobiotic strains were selected by screening with the GFP-TB in vitro model. Treatmentwith probiotic extracts significantly reduced the TB burden inside macrophagecells analyzed by confocal microscopy, ranging from 51% to 76%. Theanti-tuberculosis efficacy of these candidate strains was further evaluated usingCFU and resazurin assay s, where treatment with probiotics resulted in up to a1.25 log reduction of viable TB in the CFU assay. To ensure the probiotic strainswere safe for therapeutic application, comprehensive safety assessments wereconducted, including evaluations of cytotoxicity, antibiotic susceptibility test, hemolysis,bile salt deconjugation, and D-lactate assay. Following the safety confirmation,we investigated the underlying mechanisms by which these probiotic strainsenhance immunity and facilitate the clearance of TB within macrophage cells invitro. This involved assessing autophagy gene expression and nitrite reduction,which are established methods for studying anti-tuberculosis effects. The resultsof these mechanistic studies align with the CFU and confocal microscopy findings,indicating that at least three of the probiotic strains have the potential tomitigate tuberculosis infection significantly. This research provides a foundationfor further exploration of these probiotic strains as potential biotherapeutics intuberculosis treatment. However, further studies on toxicity, mechanism of action,and efficacy in animals, followed by clinical trials, are necessary.

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