Infections with Mycobacterium tuberculosis commonly display antibiotic treatment failure and immune evasion. The pathogen itself has several physiological properties that contribute to these resistances. Chakraborty et al. show that several mycobacterial pathogens can produce cellulose-containing biofilms. Biofilms are formed by M. tuberculosis in vitro and within granulomas in lung samples of mice, macaques, and humans. When nebulized cellulase was administered to infected mice in combination with frontline drugs such as isoniazid and rifampicin, lung tissue damage was minimal compared with controls receiving heat-inactivated cellulase. Strains of the pathogen engineered to overexpress bacterial cellulases grew well but were sensitive to antibiotics, produced deficient biofilms, and had limited capacity to cause tissue damage. Mycobacterial cellulose may represent an Achilles heel to target for tuberculosis therapies.
Nat. Commun. 12, 1606 (2021).