Tuberculostearic Acid-Containing Phosphatidylinositols as Markers of Bacterial Burden in Tuberculosis

One-fourth of the global human population is estimated to be infected with strains of the Mycobacterium tuberculosis complex (MTBC), the causative agent of tuberculosis (TB). Using lipidomic approaches, we show that tuberculostearic acid (TSA)-containing phosphatidylinositols (PIs) are molecular markers for infection with clinically relevant MTBC strains and signify bacterial burden. For the most abundant lipid marker, detection limits of ∼10$^{2}$ colony forming units (CFUs) and ∼10$^{3}$ CFUs for bacterial and cell culture systems were determined, respectively. We developed a targeted lipid assay, which can be performed within a day including sample preparation─roughly 30-fold faster than in conventional methods based on bacterial culture. This indirect and culture-free detection approach allowed us to determine pathogen loads in infected murine macrophages, human neutrophils, and murine lung tissue. These marker lipids inferred from mycobacterial PIs were found in higher levels in peripheral blood mononuclear cells of TB patients compared to healthy individuals. Moreover, in a small cohort of drug-susceptible TB patients, elevated levels of these molecular markers were detected at the start of therapy and declined upon successful anti-TB treatment. Thus, the concentration of TSA-containing PIs can be used as a correlate for the mycobacterial burden in experimental models and in vitro systems and may prospectively also provide a clinically relevant tool to monitor TB severity

Hill coefficients of dietary polyphenolic enzyme inhibitiors: can beneficial health effects of dietary polyphenols be explained by allosteric enzyme denaturing?

Inspired by a recent article by Prinz, suggesting that Hill coefficients, obtained from four parameter logistic fits to dose–response curves, represent a parameter allowing distinction between a general allosteric denaturing process and real single site enzyme inhibition, Hill coefficients of a number of selected dietary polyphenol enzyme inhibitions were compiled from the available literature. From available literature data, it is apparent that the majority of polyphenol enzyme interactions reported lead to enzyme inhibition via allosteric denaturing rather than single site inhibition as judged by their reported Hill coefficients. The results of these searches are presented and their implications discussed leading to the suggestion of a novel hypothesis for polyphenol biological activity termed the insect swarm hypothesis