Discovery of host lipid biomarkers for tuberculosis infection in mice

Abstract

With the re-emergence of tuberculosis (TB), caused by Mycobacterium tuberculosis, and the increased incidence of drug resistant strains, the need for novel drugs is urgent. Surrogate markers, which can help to assess efficacy in clinical and pre-clinical trials of such drugs, will tremendously impact the validation of new TB chemotherapeutics.Here we develop an analytical approach based on the analysis of host lipid profiles. Whole blood lipids of healthy, TB-infected and TB-infected and drug-treated, i.e. cured, mice were quantified by mass spectrometry. Support vector machines were trained, optimized and subsequently shown to discriminate between the three groups with high accuracy. Further analysis of individual lipid molecular species revealed lipids whose levels revert to their respective healthy state upon treatment.This new approach can therefore potentially identify biomarkers of drug response in pre-clinical trial and may in the future help to shorten clinical studies.