Impact of Mycobacterium ulcerans Biofilm on Transmissibility to Ecological Niches and Buruli Ulcer Pathogenesis

Abstract

The role of biofilms in the pathogenesis of mycobacterial diseases remains largely unknown. Mycobacterium ulcerans, the etiological agent of Buruli ulcer, a disfiguring disease in humans, adopts a biofilm-like structure in vitro and in vivo, displaying an abundant extracellular matrix (ECM) that harbors vesicles. The composition and structure of the ECM differs from that of the classical matrix found in other bacterial biofilms. More than 80 proteins are present within this extracellular compartment and appear to be involved in stress responses, respiration, and intermediary metabolism. In addition to a large amount of carbohydrates and lipids, ECM is the reservoir of the polyketide toxin mycolactone, the sole virulence factor of M. ulcerans identified to date, and purified vesicles extracted from ECM are highly cytotoxic. ECM confers to the mycobacterium increased resistance to antimicrobial agents, and enhances colonization of insect vectors and mammalian hosts. The results of this study support a model whereby biofilm changes confer selective advantages to M. ulcerans in colonizing various ecological niches successfully, with repercussions for Buruli ulcer pathogenesis.

Bacillus anthracis produces membrane-derived vesicles containing biologically active toxins

“…This result confirms and extends reports of vesicular structures in other Gram-positive microbes, such as S. aureus (21), M. ulcerans (19), and in Bacillus cereus and Bacillus subtillis (18). However, by demonstrating that these structures serve as a vesicular transport system for anthrax toxins, we associate vesicle production with the delivery of virulence components, as has been shown to such Gram-negative pathogens as Escherichia coli (28, 29), P. aeruginosa (14,17,30), and Helicobacter pylori (31) and Cryptococcus neoformans (12,13).…”

“…More recently, the release of membrane-derived vesicles by Grampositive Staphylococcus aureus, Mycobacterium ulcerans, and Bacillus spp. was reported (18)(19)(20)(21), suggesting that vesicle production is a widespread phenomenon among microbial species.…”

Bacterial strategies to overcome insect defences

“…M. ulcerans can proliferate to colonize the salivary canals and the inside cavity of the raptorial legs, where it synthesizes an extracellular matrix that promotes formation of a biofilm-like structure 89 . This matrix is important for bacterial translocation, and its presence enhances colonization of insect vectors and mammalian hosts 91 . It has been proposed that N. cimicoides can also serve as a vector that contributes to the dissemination of M. ulcerans 90 .…”

Disruption of <i>Mycobacterium smegmatis</i> Biofilms Using Bacteriophages Alone or in Combination with Mechanical Stress

“…Future studies will focus on the molecular characterization of phages, like CU 14A, which are highly effective in reducing biofilms. The approaches described here could also be applied to isolating phages to disrupt environmental biofilms of known human pathogens like M. marinum and M. ulcerans [18] [19].…”