| Popis: |
Sulfated metabolites are abundant in higher eukaryotes, where they play roles in cell-to-cell communication. This chapter highlights recent advances in the understanding of sulfolipid-1 (SL-1) biosynthesis and discusses the potential biological significance of SL-1 and other sulfated metabolites in the context of both historical observations and modern experiments. Sequencing of the Mycobacterium tuberculosis genome in 1998 provided the tools necessary to draw links from gene to protein and metabolite. A signaturetag mutagenesis (STM) screen identified mmpL7 as a gene essential for M. tuberculosis growth in a mouse model of infection. Sulfate ester functionality distinguishes SL-1 from other well-characterized mycobacterial lipids. Recently, Gap, a small integral membrane protein from Mycobacterium smegmatis was shown to be required for transport of glycopeptidolipids to the cell surface. In vivo analysis of the Δpks2 mutants left the SL-1 community questioning the importance of the molecule that had previously garnered so much attention. Attenuation of the ΔmmpL8 mutant in the persistent stage of M. tuberculosis infection contrasts with the reported phenotype of the Δpks2 mutants. Although M. tuberculosis is the most extensively studied species of the mycobacterial genus, several other mycobacteria have medical importance owing to their synergism with human immunodeficiency virus. One such species is the opportunistic environmental mycobacterium Mycobacterium avium, which preferentially infects individuals with compromised immunity. This pathogen also encodes nine putative sulfotransferases, the largest number of sulfotransferases of any sequenced mycobacterial species. As one's knowledge of human immunity grows, better cellular and in vivo models for M. tuberculosis virulence will be created. |
