Glucosylglycerate metabolism, bioversatility and mycobacterial survival

Abstract

Despite the progressive decline in tuberculosis mortality, strains resistant to our dated antibiotics remain a global threat, as are the emerging nontuberculous mycobacteria, ubiquitous in natural and human environments. This pressing situation boosted by debilitated immune systems, chronic illness and the aged population calls for efficient strategies to fight these successful organisms, and identifying pathways critical for their survival is a crucial step towards this goal. In this context, the glycoside glucosylglycerate (GG) has been implicated in the adaptation of mycobacteria to nitrogen starvation and to thermal stress, and the key gene for GG synthesis has been considered essential for Mycobacterium tuberculosis growth. The many organisms we now know to have genes for GG metabolism opened new exciting avenues of research into its functions, hinting for example at hypothetical roles as an inter-cellular messenger among bacteria and in microbe-plant interactions, or at key roles in the global nitrogen cycle beyond what cyanobacteria and mycobacteria have taught us so far. Indeed, the insights into GG biology gained over the last decade have changed the perception of GG from a rare polysaccharide constituent to a widespread molecule with multiple functions and biosynthetic origins. It is now possible to build upon this knowledge and further explore its physiological importance in both pathogenic and environmentally relevant microorganisms. In particular, the vital roles of GG and of its important derivative the mycobacterial methylglucose lipopolysaccharide (MGLP) discussed here are now evident, making their metabolic links attractive targets for the development of new urgently needed antimycobacterial therapies.