Structural studies of cord factors from Mycobacterium simiae related to the capacity for tumour necrosis factor alpha (α-TNF) induction

Abstract

The structure of cord factor was studied in several strains ofMycobacterium simiae, including ‘habana’ TMC 5135, considered as highly immunogenic in experimental tuberculosis and leprosy. The mycolic acids liberated from cord factor were identified in all cases asα′-,α- and keto-mycolates. According to the general NMR and MS data,α′-mycolates were mono-unsaturated and contained from 64 to 68 carbon atoms, whereasα-mycolates mainly presented two 2,3-disubstituted cyclopropane rings and a chain length of 80–91 carbon atoms; keto-mycolates mostly contained one cyclopropane ring and 85–91 carbon atoms. Taking into account the1H-NMR results, strains varied in the ratio of the different mycolates, and the high levels of keto-mycolates found in the cord factors of TMC 5135 and ATCC 25275Tstood out. Notably, MS revealed that the odd carbon number series ofα-mycolates (C87–C89) predominated in the cord factor of TMC 5135, in contrast to the remaining studied strains, in which the even (C84–C86) and odd carbon number series appeared more equal. The fine structural differences detected among the cord factors studied did not seem to be relevant to the general capacity of these molecules to induce the secretion of tumour necrosis factor alpha, as the cord factors from several strains ofM. simiae(TMC 5135, IPK-342 and ATCC 25275T) induced similar amounts of this cytokine in RAW 264.7 cells.