Council of Scientific and Industrial Research, Institute of Microbial Technology, Chandigarh, India.
Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA.
Nat Commun. 2021 Mar 11;12(1):1606. doi: 10.1038/s41467-021-21748-6.
Tuberculosis is a chronic disease that displays several features commonly associated with biofilm-associated infections: immune system evasion, antibiotic treatment failures, and recurrence of infection. However, although Mycobacterium tuberculosis (Mtb) can form cellulose-containing biofilms in vitro, it remains unclear whether biofilms are formed during infection in vivo. Here, we demonstrate the formation of Mtb biofilms in animal models of infection and in patients, and that biofilm formation can contribute to drug tolerance. First, we show that cellulose is also a structural component of the extracellular matrix of in vitro biofilms of fast and slow-growing nontuberculous mycobacteria. Then, we use cellulose as a biomarker to detect Mtb biofilms in the lungs of experimentally infected mice and non-human primates, as well as in lung tissue sections obtained from patients with tuberculosis. Mtb strains defective in biofilm formation are attenuated for survival in mice, suggesting that biofilms protect bacilli from the host immune system. Furthermore, the administration of nebulized cellulase enhances the antimycobacterial activity of isoniazid and rifampicin in infected mice, supporting a role for biofilms in phenotypic drug tolerance. Our findings thus indicate that Mtb biofilms are relevant to human tuberculosis.
结核病是一种慢性疾病，具有几种与生物膜相关感染相关的特征：免疫系统逃避、抗生素治疗失败和感染复发。然而，尽管结核分枝杆菌（Mtb）可以在体外形成含有纤维素的生物膜，但仍不清楚在体内感染过程中是否形成生物膜。在这里，我们在感染动物模型和患者中证明了 Mtb 生物膜的形成，并且生物膜的形成可能导致药物耐受性。首先，我们表明纤维素也是快速和慢速生长非结核分枝杆菌体外生物膜细胞外基质的结构成分。然后，我们使用纤维素作为生物标志物来检测实验感染小鼠和非人类灵长类动物肺部以及从肺结核患者获得的肺组织切片中的 Mtb 生物膜。生物膜形成缺陷的 Mtb 菌株在小鼠中的存活能力减弱，表明生物膜可保护细菌免受宿主免疫系统的攻击。此外，雾化纤维素酶的给药增强了异烟肼和利福平在感染小鼠中的抗分枝杆菌活性，支持生物膜在表型药物耐受性中的作用。因此，我们的发现表明 Mtb 生物膜与人类结核病有关。
