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Mervyn Beukes Yolandy Lemmer Madrey Deysel Juma’a R. Al Dulayymi Mark S. Baird Gani Koza Maximiliano M. Iglesias Richard R. Rowles Cornelia Theunissen Johan Grooten Gianna Toschi Vanessa V. Roberts Lynne Pilcher Sandra Van Wyngaardt Nsovo Mathebula Mohammed Balogun Anton C. Stoltz Jan A. Verschoor 《Chemistry and physics of lipids》2010,163(8):800-808
Cell wall mycolic acids (MA) from Mycobacterium tuberculosis (M.tb) are CD1b presented antigens that can be used to detect antibodies as surrogate markers of active TB, even in HIV coinfected patients. The use of the complex mixtures of natural MA is complicated by an apparent antibody cross-reactivity with cholesterol. Here firstly we report three recombinant monoclonal scFv antibody fragments in the chicken germ-line antibody repertoire, which demonstrate the possibilities for cross-reactivity: the first recognized both cholesterol and mycolic acids, the second mycolic acids but not cholesterol, and the third cholesterol but not mycolic acids. Secondly, MA structure is experimentally interrogated to try to understand the cross-reactivity. Unique synthetic mycolic acids representative of the three main functional classes show varying antigenicity against human TB patient sera, depending on the functional groups present and on their stereochemistry. Oxygenated (methoxy- and keto-) mycolic acid was found to be more antigenic than alpha-mycolic acids. Synthetic methoxy-mycolic acids were the most antigenic, one containing a trans-cyclopropane apparently being somewhat more antigenic than the natural mixture. Trans-cyclopropane-containing keto- and hydroxy-mycolic acids were also found to be the most antigenic among each of these classes. However, none of the individual synthetic mycolic acids significantly and reproducibly distinguished the pooled serum of TB positive patients from that of TB negative patients better than the natural mixture of MA. This argues against the potential to improve the specificity of serodiagnosis of TB with a defined single synthetic mycolic acid antigen from this set, although sensitivity may be facilitated by using a synthetic methoxy-mycolic acid. 相似文献
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Mervyn Beukes Yolandy Lemmer Madrey Deysel Juma’a R. Al Dulayymi Mark S. Baird Gani Koza Maximiliano M. Iglesias Richard R. Rowles Cornelia Theunissen Johan Grooten Gianna Toschi Vanessa V. Roberts Lynne Pilcher Sandra Van Wyngaardt Nsovo Mathebula Mohammed Balogun Anton C. Stoltz Jan A. Verschoor 《Chemistry and physics of lipids》2011,(2):175
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Benadie Y Deysel M Siko DG Roberts VV Van Wyngaardt S Thanyani ST Sekanka G Ten Bokum AM Collett LA Grooten J Baird MS Verschoor JA 《Chemistry and physics of lipids》2008,152(2):95-103
Mycolic acids (MAs) are a major component of the cell walls of Mycobacterium tuberculosis and related organisms. These alpha-alkyl beta-hydroxy long fatty acids have been the subject of numerous studies for their immunological properties. We previously reported that an interaction between cholesterol and mycolic acids could be responsible for the low accuracy in the serodiagnosis of TB when using free mycolic acid in an ELISA assay. The aim of this work was to investigate if this interaction could be due to a similarity in the structural properties between mycolic acids and cholesterol. The investigation revealed that patient sera cross-reacted with mycolic acids and cholesterol in an ELISA experiment suggesting that both molecules may present related functionality in a similar structural orientation. This relation was further supported by the interaction of mycolic acids with Amphotericin B (AmB), a known binding agent to ergosterol and cholesterol. Using a resonant mirror biosensor, we observed that AmB recognised both cholesterol and mycolic acids. In addition, a specific attraction was observed between mycolic acid and cholesterol by the accumulation of cholesterol from liposomes in suspension onto immobilized mycolic acids containing liposomes, detected with a biosensor technique. Combined, these results suggest that mycolic acids can assume a three-dimensional conformation similar to a sterol. This requires that mycolic acid exposes its hydroxyl group and assumes rigidity in its chain structure to generate a hydrophobic surface topology matching that of cholesterol. A particular folded conformation would be required for this, of which a few different types have already been proven to exist in monolayers of mycolic acids. 相似文献
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