Lee Youngkyoung, Seo Hoonhee, Lee Soyeon, Choi Dongsic, Kim Sukyung, Rahim Md Abdur, Song Ho-Yeon
Department of Microbiology and Immunology, School of Medicine, Soonchunhyang University, Cheonan, Chungnam, 31151, Korea.
Human Microbiome Medical Research Center (HM·MRC), School of Medicine, Soonchunhyang University, Asan, Chungnam, 31538, Korea.
Med Microbiol Immunol. 2025 Sep 19;214(1):43. doi: 10.1007/s00430-025-00851-1.
Tuberculosis remains a severe global health threat, exacerbated by the rising prevalence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis. Despite the urgent need for effective interventions, the development of anti-tuberculosis drugs has been slow, and the emergence of pan-drug-resistant strains underscores the critical need for innovative therapeutic strategies. This study introduces Bacillus sonorensis PMC204, a novel probiotic strain with potent anti-tuberculosis properties identified through extensive screening. PMC204 significantly reduced M. tuberculosis H37Rv and XDR strains within Raw 264.7 macrophage cells. Moreover, membrane vesicles (MVs) derived from this strain exhibited superior inhibitory effects against both standard and XDR strains of M. tuberculosis. Proteomic analysis of the isolated MVs revealed a high abundance of flagellin proteins, which are hypothesized to play a pivotal role in the observed anti-tuberculosis effects. These findings also suggest a close link between the therapeutic efficacy of PMC204 and autophagy activation. Safety assessments further demonstrated the feasibility of PMC204 as a potential anti-tuberculosis therapeutic. The anti-tuberculosis activity of bacterial MVs represents an innovative approach in microbiome therapeutics, positioning PMC204 as a next-generation probiotic distinct from conventional strains. This study contributes to advancing the field of microbiome-based therapeutics and presents promising avenues for managing drug-resistant tuberculosis.
结核病仍然是全球严重的健康威胁，耐多药（MDR）和广泛耐药（XDR）结核分枝杆菌患病率的上升加剧了这一威胁。尽管迫切需要有效的干预措施，但抗结核药物的研发进展缓慢，全耐药菌株的出现凸显了创新治疗策略的迫切需求。本研究介绍了声芽孢杆菌PMC204，这是一种通过广泛筛选鉴定出的具有强大抗结核特性的新型益生菌菌株。PMC204显著降低了Raw 264.7巨噬细胞内的结核分枝杆菌H37Rv和XDR菌株。此外，源自该菌株的膜囊泡（MVs）对结核分枝杆菌的标准菌株和XDR菌株均表现出卓越的抑制作用。对分离出的MVs进行蛋白质组学分析发现，鞭毛蛋白含量很高，据推测这些蛋白在观察到的抗结核作用中起关键作用。这些发现还表明PMC204的治疗效果与自噬激活之间存在密切联系。安全性评估进一步证明了PMC204作为潜在抗结核治疗药物的可行性。细菌MVs的抗结核活性代表了微生物组治疗学中的一种创新方法，使PMC204成为一种不同于传统菌株的新一代益生菌。本研究有助于推动基于微生物组的治疗学领域的发展，并为应对耐药结核病提供了有前景的途径。
