Biofilms and Mycobacterium tuberculosis

LETTER

There is good evidence that Mycobacterium tuberculosis evolved with Homo sapiens and, like our ancestors, migrated throughout the rest of the world from Africa some 70,000 years ago (1). Since M. tuberculosis, which is now a familiar human pathogen, coexisted with other mycobacteria within different niches, it is possible that mycobacteria once coexisted with man as a symbiont, much as bacteria such as gut bacteria assist and benefit mankind now. Related to this is the ability of mycobacteria, including M. tuberculosis, to form biofilms. A number of bacteria form biofilms, which likely helps them grow and communicate like Pseudomonas aeruginosa, which is associated with the disease cystic fibrosis. For human pathogens, biofilm growth helps bacteria become more tolerant of antibiotics and persist in chronic disease and to elicit different immune responses which can affect the efficacy of vaccines (2). This is good for the bacteria. In the case of certain mycobacteria, biofilms coat medical devices and are a nemesis of patients in hospitals. Biofilms require a matrix, and, for M. tuberculosis, species-specific mycolic acids (3) or complex sugars (4) or DNA (5) may be utilized. Anyone who has cultured mycobacteria in a laboratory has noticed the peculiar aggregated growth. They seldom grow as single organisms. Indeed, growth of tuberculosis (TB) organisms as pellicles in stationary cultures, which is the method used by most manufacturers of Mycobacterium bovis BCG vaccine, occurs in the form of biofilms and new recombinant BCG vaccines cultured in fermenters may differ in safety and efficacy. In a recent issue of Infection and Immunity, Wright et al. (6) showed that mycobacterial membrane protein large (MmpL), a cell wall lipid transporter, is essential for the formation of biofilms in M. tuberculosis. The investigators used a unique in vitro granuloma model generated from peripheral blood mononuclear cells (PBMC) and containing macrophages, multinucleated giant cells, T cells, and B cells to suggest that biofilms are important in vivo in granulomas. The results of those studies affirm the importance of biofilms in tuberculosis and imply that biofilms are underappreciated in M. tuberculosis pathogenesis. Additional investigations are needed to determine if TB vaccines manufactured from biofilms are more efficacious, if biofilm growth in vivo affects the pathogenesis of tuberculosis, and if vaccines produced from mycobacterial biofilms may be more effective against different stages of the disease such as the chronic phase.