trehalose-monomycolate and bedaquiline

The mycomembrane layer of the mycobacterial cell envelope is a barrier to environmental, immune, and antibiotic insults. There is considerable evidence of mycomembrane plasticity during infection and in response to host-mimicking stresses. Since mycobacteria are resource and energy limited under these conditions, it is likely that remodeling has distinct requirements from those of the well-characterized biosynthetic program that operates during unrestricted growth. Unexpectedly, we found that mycomembrane remodeling in nutrient-starved, nonreplicating mycobacteria includes synthesis in addition to turnover. Mycomembrane synthesis under these conditions occurs along the cell periphery, in contrast to the polar assembly of actively growing cells, and both liberates and relies on the nonmammalian disaccharide trehalose. In the absence of trehalose recycling,

Topics: Adenosine Triphosphate; Anti-Bacterial Agents; ATP-Binding Cassette Transporters; Bacterial Proteins; Cell Membrane; Cell Wall; Cord Factors; Diarylquinolines; Energy Metabolism; Galactans; Gene Expression; Glucose; Maltose; Membrane Transport Proteins; Mycobacterium smegmatis; Mycobacterium tuberculosis; Mycolic Acids; Rifampin; Trehalose