NIH R01 · 2024
Chemical biology studies of MmpL3 inhibition and resistance in mycobacteria
MmpL3 (Mycobacterium membrane protein Large 3) is a common target of inhibitors of mycobacterial growth identified by whole cell, phenotypic, high throughput screens. MmpL3 is a mycolate flippase that moves trehalose monomycolate (TMM) to the pseudoperiplasmic space, from where TMM is modified to trehalose dimycolate (TDM) and incorporated into the mycomembrane. Mycobacterium tuberculosis (Mtb) and M. smegmatis mmpL3 knockdown strains show that mmpL3 is essential for survival both in vitro and in mice. This phenotype makes MmpL3 an attractive therapeutic target and supports efforts to characterize molecules targeting MmpL3. Multiple MmpL3 inhibitors exhibit synergistic interactions with TB…
From the public funding record at NIH RePORTER. Describes the funded project, not the reviews below.