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 ∼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. 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.
Council of Scientific and Industrial Research, Institute of Microbial Technology, Sector 39A, Chandigarh 160036, India.
Abhishek
A
Trivedi
Council of Scientific and Industrial Research, Institute of Microbial Technology, Sector 39A, Chandigarh 160036, India.
Parminder Singh
PS
Mavi
Council of Scientific and Industrial Research, Institute of Microbial Technology, Sector 39A, Chandigarh 160036, India.
Deepak
D
Bhatt
Council of Scientific and Industrial Research, Institute of Microbial Technology, Sector 39A, Chandigarh 160036, India.
Ashwani
0000-0002-6240-6810
A
Kumar
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D018441:Biofilms / Q000187:drug effects*; D002482:Cellulose / Q000737:chemistry / Q000378:metabolism*; D004229:Dithiothreitol / Q000494:pharmacology*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism
D001426:Bacterial Proteins; D009243:NAD; D009249:NADP; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D002482:Cellulose; D004229:Dithiothreitol