Fig. 9. Mycobacterial biofilms protect the resident bacilli from antimycobacterial agents.

a Schematic representation of Mtb infection followed by drug treatment regime in mice (n = 4, an experiment performed twice). b–d Gross lung pathology, histopathology analysis, and pathology scoring of mice lungs infected with Mtb, followed by treatment. e, f CBD-mCh staining and quantification (using NIS elements) in lung sections of Mtb infected mice subsequently treated as described in a. g Survival of Mtb inside mice 2 and 4 weeks post-treatment with Rif and INH orally and/or cellulase or heat-inactivated cellulase through nebulization. h Schematic representation of Mtb biofilms inside the human lungs. Infection with Mtb leads to the formation of granulomatous lesions in the human lungs. A granuloma is a compact immunological structure predominated by macrophages at the center, which, in turn, differentiate into other cell types like foamy macrophages and multinucleate giant cells having lipid droplets, in a specialized manner. The periphery of the granuloma is comprised of T and B lymphocytes. However, in our proposition, the necrotic core of the granuloma, consisting of Mtb bacilli is structured as a biofilm, which is composed of extracellular matrix including cellulose as one of the major components, can act as a barrier to both antimycobacterial agents as well as a host defense mechanism, thus rendering protection to the bacteria. The data presented in figures d, f and g have been plotted in GraphPad Prism 6 and represented as mean (±s.e.m). Statistical significance of g was determined using two way ANOVA, *P < 0.05 and statistical significance of d and f were determined using Student’s t-test (two tailed). *P < 0.05, ***P < 0.0001. For d *P = 0.0205 and for f ***P < 0.0001. All data are representative of three independent biological experiments performed in triplicates unless otherwise mentioned. Scale bars correspond to 200 μm. All source data are provided as a Source Data file.