Tuberculosis metabolomics reveals adaptations of man and microbe in order to outcompete and survive

Abstract

Despite numerous research efforts to control tuberculosis, it is still regarded as a global pandemic. It is clear that the infectious agent responsible and its associated disease mechanisms remain poorly understood. Alternative research strategies are therefore urgently needed to better characterize active-TB, especially the adaptations of the host and microbe as they compete to survive. Using a GCxGC-TOFMS metabolomics approach, we identified new urinary TB metabolite markers induced by adaptations of the host metabolome and/or host-pathogen interactions. The most significant of these were the TB-induced changes resulting in abnormal host fatty acid and amino acid metabolism, in particular to tryptophan, phenylalanine and tyrosine, inducing a metabolite profile similar to that of patients suffering from phenylketonuria, mediated through changes to INF-c and possibly insulin. This subsequently also explains some of the symptoms associated with TB and provides clues to better treatment approaches.