Abstract
Mycobacterium tuberculosis (Mtb) encodes several bacterial effectors impacting the colonization of phagocytes. LppM (Rv2171) is both implicated in phagocytosis and able to efficiently block phagosomal acidification in the macrophage, two key processes contributing to Mtb persistence. We show that LppM is anchored to the mycobacterial cell wall by a C-terminal membrane domain. However, the protein also exists as a truncated protein secreted into the culture medium. The LppM solution structure we solve here displays no similarity with other Mtb lipoproteins also involved in phagosomal maturation (i.e., LprG). In addition, we demonstrate that the protein may be able to bind rare molecular species of phosphatidylinositol mannosides, bacterial compounds known to affect the host immune response. Thus, our data demonstrate a dual localization of LppM and provide a unique perspective on the regulation of protein secretion and localization in Mtb.