Exploring the mechanism of BDL regimen in the treatment of drug-resistant tuberculosis: an exploratory review integrating pharmacology, network pharmacology, and transcriptomics
Description
Drug-resistant tuberculosis (DR-TB) poses a persistent threat to global health, necessitating the exploration of novel therapeutic strategies. The combination of bedaquiline, delamanid, and linezolid (BDL) has emerged as a pivotal regimen in the clinical management of DR-TB; however, the precise molecular mechanisms underlying its potential synergy remain incompletely characterized. In this integrative review, we synthesize pharmacological principles, network pharmacology, and bioinformatics analyses to elucidate the multi-target action and host-pathogen interaction networks modulated by the BDL combination. Our analysis delineates the distinct pharmacological roles of each agent—bedaquiline targeting ATP synthase, delamanid disrupting cell wall biosynthesis, and linezolid inhibiting protein synthesis—and further explores their potential synergistic interplay. Through systems biology approaches, we predict potential hub genes (e.g., IFNG, MAPK14) and in silico identification of key signaling pathways. including HIF-1 and PD-L1, suggesting a dual mechanism of direct bactericidal activity coupled with host immune modulation. Furthermore, we contextualize these molecular findings with a critical review of existing clinical evidence, highlighting both the efficacy trends and the heterogeneity in current observational data. This review serves as a hypothesis-generating framework, providing a theoretical basis for understanding the BDL regimen's mechanism of action and guiding future research towards validating these predicted molecular targets and pathways.