RBCG-LTAK63 enhances protection against tuberculosis by inducing autophagy and circadian gene regulation.

ABSTRACT: Tuberculosis (TB) remains a global public health challenge, with the current BCG vaccine providing limited efficacy in adults, and available treatments being lengthy and debilitating. To overcome these challenges, we have previously developed a recombinant BCG strain expressing the detoxified E. coli Heat-Labile Toxin (LTAK63), providing increased protection in mouse models and reduced lung pathology. Here, using systems biology and RNA sequencing of lung tissues in a murine model, we uncover the molecular mechanisms underlying rBCG-LTAK63's increased protection. Immunization triggered early activation of cAMP-related pathways, leading to hypoxia, autophagy, and circadian rhythm gene regulation. These processes were associated with an enhanced innate immunity and promoted long-lasti

SUBMITTER: Marques-Neto LM 

PROVIDER: S-EPMC12592191 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature