Primary structure of scorpion anti-insect toxins isolated from the venom of Leiurus quinquestriatus quinquestriatus

AbstractThe amino acid sequences of insect-selective scorpion toxins, purified from the venom of Leiurus quinquestriatus quinquestriatus, have been determined by automatic phenyl isothiocyanate degradation of the S-carboxymethylated proteins and derived proteolytic peptides. The excitatory toxin Lqq IT1 and Lqq IT1' (70 residues) show the shift of one half-cystine from an external position, which is characteristic of anti-mammal toxins, to an internal sequence position. Lqq IT2, (61 residues) displays the half-cystine residue in position 12, common to the sequence of all known antimammal toxins; it induces flaccid paralysis on insects but is non-toxic for the mouse. Lqq IT2, structurally defines a new type of anti-insect toxins from scorpion venoms. CD spectra and immunological data are in agreement with this finding

Comparative investigation of the pathogenicity of three Mycobacterium tuberculosis mutants defective in the synthesis of p-hydroxybenzoic acid derivatives.

p-Hydroxybenzoic acid derivatives (p-HBADs) are glycoconjugates secreted by all Mycobacterium tuberculosis isolates whose contribution to pathogenicity remains to be determined. The pathogenicity of three transposon mutants of M. tuberculosis deficient in the biosynthesis of some or all forms of p-HBADs was studied. Whilst the mutants grew similarly to the wild-type strain in macrophages and C57BL/6 mice, two of the mutants induced a more severe and diffuse inflammation in the lungs. The lack of production of some or all forms of p-HBADs in these two mutants also correlated with an increased secretion of the pro-inflammatory cytokines tumour-necrosis factor α, interleukin 6 and interleukin 12 in vivo. We propose that the loss of production of p-HBADs by tubercle bacilli results in their diminished ability to suppress the pro-inflammatory response to infection and that this ultimately provokes extensive pulmonary lesions in the C57BL/6 model of tuberculosis infection

Characterization of a Truncated Lipoarabinomannan from the Actinomycete Turicella otitidis

Lipoarabinomannan (LAM) lipoglycans have been characterized from a range of mycolic acid-containing actinomycetes and from the amycolate actinomycete Amycolatopsis sulphurea. To further understand the structural diversity of this family, we have characterized the lipoglycan of the otic commensal Turicella otitidis. T. otitidis LAM (TotLAM) has been determined to consist of a mannosyl phosphatidylinositol anchor unit carrying an (α 1→6)-linked mannan core and substituted with terminal-arabinosyl branches. Thus, TotLAM has a novel truncated LAM structure. Using the human monocytic THP-1 cell line, it was found that TotLAM exhibited only minimal ability to induce tumor necrosis factor alpha. These findings contribute further to our understanding of actinomycete LAM diversity and allow further speculation as to the correlation between LAM structure and the immunomodulatory activities of these lipoglycans

Fatty acyl structures of mycobacterium tuberculosis sulfoglycolipid govern T cell response

CD1b-restricted T lymphocytes recognize a large diversity of mycobacterial lipids, which differ in their hydrophilic heads and the structure of their acyl appendages. Both moieties participate in the antigenicity of lipid Ags, but the structural constraints governing binding to CD1b and generation of antigenic CD1b:lipid Ag complexes are still poorly understood. Here, we investigated the structural requirements conferring antigenicity to Mycobacterium tuberculosis sulfoglycolipid Ags using a combination of CD1b:lipid binding and T cell activation assays with both living dendritic cells and plate-bound recombinant soluble CD1b. Comparison of the antigenicity of a panel of synthetic analogs, sharing the same trehalose-sulfate polar head, but differing in the structure of their acyl tails, shows that the number of C-methyl substituents on the fatty acid, the configuration of the chiral centers, and the respective localization of the two different acyl chains on the sugar moiety govern TCR recognition and T lymphocyte activation. These studies have major implications for the design of sulfoglycolipid analogs with potential use as tuberculosis subunit vaccines