Sulfolipid I of Mycobacterium tuberculosis, strain H37Rv I. Purification and properties

Goren, Mayer B.

doi:10.1016/0005-2760(70)90067-6

Cited by 120 publications

(89 citation statements)

References 7 publications

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“…C: Purifi cation schemes are shown for the different acyl forms of SGL. D: TLC analysis of the different fractions issued from the silicic column eluted by CHCl 3 (1,2), CHCl 3 /CH 3 OH 9/1 (3,4), CHCl 3 /CH 3 OH 8/2 (5, 6), CHCl 3 /CH 3 OH 7/3 (7,8), and CH 3 OH (9). AS, acetone-soluble fraction.…”

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confidence: 99%

Deciphering sulfoglycolipids of Mycobacterium tuberculosis

Layre

Paepe

Larrouy-Maumus

et al. 2011

Journal of Lipid Research

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confidence: 99%

Deciphering sulfoglycolipids of Mycobacterium tuberculosis

Layre

Paepe

Larrouy-Maumus

et al. 2011

Journal of Lipid Research

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“…The most abundant sulfatide, termed Sulfolipid-1 (SL-1), consists of a trehalose core, four fatty acyl groups, and a sulfate ester (Fig. 1A) (10)(11)(12)(13). Despite the discovery of SL-1 nearly 50 years ago, the biological function of the molecule is not known.…”

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confidence: 99%

PapA1 and PapA2 are acyltransferases essential for the biosynthesis of theMycobacterium tuberculosisvirulence factor Sulfolipid-1

Kumar

Schelle²,

Jain³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

111

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pathogenesis ͉ biochemistry ͉ glycolipid ͉ sulfation T he thick Mycobacterium tuberculosis (M. tb) cell wall consists of numerous glycolipids that are distinctive to the mycobacterial genus, including phosphatidylinositol mannosides, trehalose mycolates, and lipoarabinomannans (1). These molecules are essential for many of the characteristics that distinguish mycobacterial pathogenesis, such as the inhibition of phagosomal maturation, drug resistance, and alteration of the host immune response (2-6). A family of cell surface sulfated lipids (dubbed sulfatides) were identified in M. tb extracts and correlated to strain virulence (7-9). The most abundant sulfatide, termed Sulfolipid-1 (SL-1), consists of a trehalose core, four fatty acyl groups, and a sulfate ester (Fig. 1A) (10-13). Despite the discovery of SL-1 nearly 50 years ago, the biological function of the molecule is not known. Conflicting reports suggest a role for SL-1 in superoxide (O 2 Ϫ ) release from human neutrophils or monocytes, alteration of trehalose dimycolate toxicity, and inhibition of trehalose dimycolate-induced macrophage recruitment (14-19). The relevance of these studies to the physiological role of SL-1 in M. tb infection is debatable.Although the role of SL-1 remains elusive, advances in genetics and metabolite analysis have sped the discovery of genes, proteins, and intermediates associated with SL-1 biosynthesis (20). Currently, three proteins are known to be involved in SL-1 assembly: Stf0, Pks2, and MmpL8. The sulfotransferase Stf0 sulfates trehalose at the 2-position, forming trehalose-2-sulfate (T2S), thereby initiating SL-1 biosynthesis (21). Meanwhile, the polyketide synthase Pks2 synthesizes the phthioceranoyl and hydroxyphthioceranoyl lipids that occupy the 6-, 6Ј-, and 3Ј-positions of SL-1 (Fig. 1 A) (22). The proteins responsible for transfer of the Pks2 products and the palmitoyl group to the T2S core, and the order in which these lipids are added, have not yet been defined.Insight into the order of lipid addition came from characterization of the putative lipid transporter MmpL8 (23,24). A mutant strain, ⌬mmpL8, lacks SL-1 but accumulates the diacylated intermediate SL 1278 (named for its observed mass) inside the cell (Fig. 1B). This intermediate possesses two of the four SL-1-associated lipids: a hydroxyphthioceranoyl group at the 3Ј-position and a palmitoyl group at the 2Ј-position (24). SL 1278 was recently found to be an immunostimulant in human tuberculosis patients (25). The glycolipid is presented on the surface of M. tb-infected antigen-presenting cells by CD1b, a member of the MHC class I-like CD1 family. Intriguingly, the ⌬mmpL8 mutant, which lacks SL-1 but accumulates SL 1278 , shows attenuated virulence in mice (23,24). By contrast, a ⌬pks2 mutant, which lacks both SL-1 and SL 1278 , is indistinguishable from WT M. tb in mice and guinea pigs (23,26). These observations suggest that SL 1278 , and possibly other SL-1 intermediates, modulate M. tb pathogenesis.In our effort to define the functions of M. tb sulf...

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“…Sulfolipid-1 (SL-1), an abundant component of the cell envelope of M. tuberculosis, is the best characterized of these molecules. SL-1 has generated much interest because of its elaborate structure and the observation that its abundance correlates with strain virulence (15)(16)(17)(18)(19)(20)(21)(22). Advances in M. tuberculosis genetics and genome sequence data facilitated several contemporary studies that addressed aspects of the biosynthesis and the function of SL-1 in vivo (23)(24)(25)(26).…”

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A sulfated metabolite produced bystf3negatively regulates the virulence ofMycobacteriumtuberculosis

Mougous

Senaratne

Kim

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Sulfated molecules have been shown to modulate isotypic interactions between cells of metazoans and heterotypic interactions between bacterial pathogens or symbionts and their eukaryotic host cells. Mycobacterium tuberculosis, the causative agent of tuberculosis, produces sulfated molecules that have eluded functional characterization for decades. We demonstrate here that a previously uncharacterized sulfated molecule, termed S881, is localized to the outer envelope of M. tuberculosis and negatively regulates the virulence of the organism in two mouse infection models. Furthermore, we show that the biosynthesis of S881 relies on the universal sulfate donor 3 -phosphoadenosine-5 -phosphosulfate and a previously uncharacterized sulfotransferase, stf3. These findings extend the known functions of sulfated molecules as general modulators of cell-cell interactions to include those between a bacterium and a human host.Fourier transform ion cyclotron resonance ͉ hypervirulent ͉ sulfate assimilation ͉ kinase ͉ adenosine-5-phosphosulfate A wide variety of organisms use sulfated molecules to control extracellular events. In mammals, sulfation of tyrosine residues on cell surface proteins is important for the interactions of chemokines with certain chemokine receptors, and for viral binding and entry (1-6). Sulfated glycans modulate processes such as leukocyte homing to lymph nodes, clearance of serum glycoproteins, and blood coagulation (7-9). Members of the glypican family that are modified with sulfated glycosaminoglycans guide organ development in Drosophila by maintaining a morphogen concentration gradient (10).In bacteria, sulfated glycolipids have been shown to serve as extracellular signaling molecules (11). The nitrogen fixing bacterium Sinorhizobium meliloti secretes the nodulation factor NodRm-1, a tetrasaccharide bearing both sulfate and lipid modifications (12). This molecule binds a receptor on the host plant, normally alfalfa, and induces root nodule formation. The sulfate group is critical for the function of NodRm-1, because the unsulfated form fails to induce root nodulation in alfalfa. In the rice blight-causing pathogen Xanthomonas oryzae, several genes involved in the synthesis of sulfated metabolites have been identified as avirulence factors with respect to certain host strains (13,14). These examples suggest that bacterial sulfated metabolites can participate in dialogue with eukaryotic hosts, analogous to their role in mammalian cell-cell communication.Mycobacteria produce an unusually complex array of sulfated structures (11). Sulfolipid-1 (SL-1), an abundant component of the cell envelope of M. tuberculosis, is the best characterized of these molecules. SL-1 has generated much interest because of its elaborate structure and the observation that its abundance correlates with strain virulence (15)(16)(17)(18)(19)(20)(21)(22). Advances in M. tuberculosis genetics and genome sequence data facilitated several contemporary studies that addressed aspects of the biosynthesis and the function of SL-1 in v...

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Sulfolipid I of Mycobacterium tuberculosis, strain H37Rv I. Purification and properties

Cited by 120 publications

References 7 publications

Deciphering sulfoglycolipids of Mycobacterium tuberculosis

Deciphering sulfoglycolipids of Mycobacterium tuberculosis

PapA1 and PapA2 are acyltransferases essential for the biosynthesis of theMycobacterium tuberculosisvirulence factor Sulfolipid-1

A sulfated metabolite produced bystf3negatively regulates the virulence ofMycobacteriumtuberculosis

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