Biofilm formation in the lung contributes to virulence and drug tolerance of Mycobacterium tuberculosis.
Biofilm formation in the lung contributes to virulence and drug tolerance of Mycobacterium tuberculosis.
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DOI：
10.1038/s41467-021-21748-6
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发表时间：
2021-03-11
影响因子：
16.6
通讯作者：
Kumar A
中科院分区：
文献类型：
--
作者：
Chakraborty P;Bajeli S;Kaushal D;Radotra BD;Kumar A
结核病是一种慢性疾病，通常表现出与生物膜相关感染相关的几个特征：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）可以在体外形成含纤维素的生物膜，但仍不清楚生物膜是否在体内感染过程中形成。在这里，我们证明了结核分枝杆菌生物膜在感染的动物模型和患者中的形成，并且生物膜的形成有助于药物耐受性。首先，我们发现纤维素也是快速和缓慢生长的非结核分枝杆菌体外生物膜的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的肺部以及从结核病患者获得的肺组织切片中的Mtb生物膜。生物膜形成缺陷的结核分枝杆菌菌株在小鼠中的存活率降低，表明生物膜保护杆菌免受宿主免疫系统的侵害。此外，雾化纤维素酶的管理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，我们的研究结果表明，结核分枝杆菌生物膜与人类结核病有关。结核分枝杆菌在体外形成生物膜，但尚不清楚生物膜是否也在体内感染过程中形成。在这里，Chakraborty等人证明了在感染的动物模型和结核病患者中生物膜的形成，并且生物膜的形成可以有助于药物耐受性。
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. Mycobacterium tuberculosis forms biofilms in vitro, but it is unclear whether biofilms are also formed during infection in vivo. Here, Chakraborty et al. demonstrate the formation of biofilms in animal models of infection and in patients with tuberculosis, and that biofilm formation can contribute to drug tolerance.
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影响因子：
7.8
作者：
Dey B;Bishai WR
通讯作者：
Bishai WR
DOI：
10.1378/chest.30.6.642
发表时间：
1956-01-01
期刊：
DISEASES OF THE CHEST
影响因子：
--
作者：
DARZINS, E;FAHR, G
通讯作者：
FAHR, G
影响因子：
3
作者：
Kongruang, S;Han, MJ;Penner, MH
通讯作者：
Penner, MH
影响因子：
3.6
作者：
DIN, N;FORSYTHE, IJ;KILBURN, DG
通讯作者：
KILBURN, DG
影响因子：
3.3
作者：
Ackart DF;Hascall-Dove L;Caceres SM;Kirk NM;Podell BK;Melander C;Orme IM;Leid JG;Nick JA;Basaraba RJ
通讯作者：
Basaraba RJ