Mycolic acids as diagnostic markers for tuberculosis case detection in humans and drug efficacy in mice.
Bottom Line: Quantification of specific precursor → fragment transitions of approximately 2000 individual mycolic acids (MAs) resulted in high analytical sensitivity and specificity.Furthermore, we quantified MA species in lung tissue of TB-infected mice and demonstrated effective clearance of MA levels following curative rifampicin treatment.Thus, our results demonstrate for the first time the feasibility and clinical relevance of direct detection of mycobacterial lipids as biomarkers of TB infection.
Affiliation: Yong Loo Lin School of Medicine, Department of Biochemistry, National University of Singapore, Singapore. email@example.comShow MeSH
Related in: MedlinePlus
Mentions: MAs, α-alkyl-β-hydroxy branched chain fatty acids (for a molecular structure, see Fig 1B), are major envelope components of mycobacteria and targets of therapeutic intervention in TB. They are attractive diagnostic markers for mycobacterial infections for several reasons. (1) They are cell wall-associated bacterial molecules and are not synthesized in the human body. Thus, the presence of MAs in host tissue is indicative of bacterial infection. (2) The chemical diversity of MAs can be used for taxonomy. (3) MAs are involved in first-line recognition of bacteria during host–pathogen interactions, contributing to bacterial survival inside macrophages. For example CD1 receptors bind MAs and stimulate subpopulations of T cells, thus modulating the immune response to infection. (4) MAs represent a substantial mass fraction of bacterial cell walls and provide a stable and durable shell. Their hydrophobic nature renders low permeability to the cell wall and protects bacterial cells from dehydration. The MA biosynthetic machinery is thus an important target for antimycobacterial drugs (Barry et al, 1998; Ehrt & Schnappinger, 2007; Tonge, 2000). In fact, it is the chemical stability of MAs that permitted early methods for taxonomy and epidemiology of TB infections. Unfortunately, analysis of MAs is complicated by their hydrophobic properties and heterogeneous chemistry.
Affiliation: Yong Loo Lin School of Medicine, Department of Biochemistry, National University of Singapore, Singapore. firstname.lastname@example.org