Mycobacterium tuberculosis lipoprotein LprG binds lipoarabinomannan and determines its localization in the cell wall envelope and affects phagolysosomal fusion (MPF3P.818)

Genetic deletion of the lipoprotein LprG reduces the virulence of Mycobacterium tuberculosis (Mtb), but the function of LprG remains unclear. We report that LprG expressed in Mtb binds to lipoglycans, e.g. lipoarabinomannan (LAM). Lipoglycan binding to LprG was dependent on both insertion of lipoglycan acyl chains into a hydrophobic pocket on LprG and a novel contribution of lipoglycan polysaccharide components outside of this pocket. An lprG null mutant (MtbΔlprG) had lower levels of surface-exposed LAM, revealing a novel role for LprG in determining Mtb cell envelope structure. Furthermore, this mutant allowed accelerated Mtb phagosome-lysosome fusion, consistent with the role for LAM in blocking phagosome maturation. We propose that LprG binding to LAM facilitates its transfer from the plasma membrane into the cell envelope, increasing surface-exposed LAM, enhancing cell envelope integrity, allowing inhibition of phagosome-lysosome fusion and enhancing Mtb survival in macrophages