In Mycobacterium marinum, the homologue of Rv1500 of M.
tuberculosis encodes a
glycosyltransferase. Initially, it was suggested that this gene is involved in the synthesis of
phosphatidylinositol mannosides (PIMs), generating Ac(2)PIM(7) from Ac(2)PIM(5).
Phosphatidylinositol mannoside and its related compounds
lipomannan (LM) and
lipoarabinomannan (
LAM) have been shown to modulate the host response to an
infection with M.
tuberculosis. Here, we generated a deletion mutant of Rv1500 in M.
tuberculosis H37Rv, and analyzed the mutant using a biochemical approach as well as in vitro and in vivo
infection models. Inactivation of Rv1500 did not lead to an altered expression pattern of PIMs in M.
tuberculosis H37Rv. We found
phosphatidylinositol (PI), PIM(2), AcPIM(2), Ac(2)PIM(2), and AcPIM(6) in both strains, but were unable to detect Ac(2)PIM(7) or Ac(2)PIM(5) either in the wild type or the mutant strain. Uptake and growth of H37Rv and Rv1500 mutant strains in murine bone marrow-derived macrophages was identical, and
TNFalpha and
IL-12p40 production in mouse macrophages and dendritic cells was induced to similar levels following
infection with either strain.
Aerosol challenge of mice showed that wild type and Rv1500 mutant strains had identical growth rates in infected organs over time. We verified
mRNA expression of Rv1500 in H37Rv and conclude that Rv1500 must serve a redundant role in viability and virulence of M.
tuberculosis.