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Institut für Medizinische Mikrobiologie

Posttranslational modification of lipoprotein in mycobacteria

Lipoproteins are a heterogenous class of surface localized proteins present in all bacteria. Lipoproteins are subjected to extensive post-translational modifications and characterized by the presence of a membrane anchor. Mycobacteria manipulate host-defense mechanisms by lipoprotein-TLR2 interaction. We have identified lipoprotein synthesis as an important virulence factor involved in Mycobacterium tuberculosis pathogenesis. Using Mycobacterium smegmatis, a non-pathogenic, fast growing Mycobacterium and Streptomyces as a model system, we dissect mycobacterial lipoprotein synthesis and transport at the genetic, biochemical and structural level. Furthermore we study the role of specific lipoporteins in mycobacterial physiology and virulence.

Lipoprotein synthesis and transport in mycobacteria
Lipoprotein synthesis and transport in mycobacteria

Lipoproteins are secreted and modified by Lgt, LspA, Lnt and eventually Pmt. Lol-homologues (E. coli nomenclature) have not yet been identified in mycobacteria but proteins with analogous functions have to be postulated.

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Attenuation

Lung pathology of BALB/c mice infected with M. tuberculosis H37Rv (A) and an lspA deletion mutant, lspA::aph (B) at 6 weeks after infection.