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Title: Thiol reductive stress induces cellulose-anchored biofilm formation in Mycobacterium tuberculosis

Mycobacterium tuberculosis (Mtb) forms biofilms harbouring antibiotic-tolerant bacilli in vitro, but the factors that induce biofilm formation and the nature of the extracellular material that holds the cells together are poorly understood. Here we show that intracellular thiol reductive stress (TRS) induces formation of Mtb biofilms in vitro, which harbour drug-tolerant but metabolically active bacteria with unchanged levels of ATP/ADP, NAD+/NADH and NADP+/NADPH. The development of these biofilms requires DNA, RNA and protein synthesis. Transcriptional analysis suggests that Mtb modulates only similar to 7% of its genes for survival in biofilms. In addition to proteins, lipids and DNA, the extracellular material in these biofilms is primarily composed of polysaccharides, with cellulose being a key component. Lastly, our results contribute to a better understanding of the mechanisms underlying Mtb biofilm formation, although the clinical relevance of Mtb biofilms in human tuberculosis remains unclear.
Authors:
 [1] ;  [1] ;  [1] ;  [1]
  1. Inst. of Microbial Technology, Chandigarh (India). Council of Scientific and Industrial Research
Publication Date:
OSTI Identifier:
1270967
Grant/Contract Number:
FG02-93ER20097
Type:
Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 7; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Research Org:
University of Georgia Research Foundation
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22) Chemical Sciences, Geosciences and Biosciences Div.; CSIR; DST, DBT India
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES gene-expression; pseudomonas-aeruginosa; escherichia-coli; bacterial biofilms; redox homeostasis; stationary-phase; growth; cell; dna; pathogenesis