A glance over drug detoxification systems through the transcriptomic profiling of Mycobacterium tuberculosis during lipid metabolism

Tuberculosis (TB) is currently the number one killer among infectious diseases worldwide. Lipids are abundant molecules during the infectious cycle of Mycobacterium tuberculosis (Mtb) and studies better mimicking its actual metabolic state during pathogenesis are needed. Though most studies have focused on the mycobacterial lipid metabolism under standard conditions (carbon source, drugs, stress), little is known about the transcriptome of Mtb in a lipid environment. Here we determine the transcriptome of Mtb H37Rv in a lipid-rich environment (mixture of cholesterol, palmitic, stearic and oleic acids), under aerobic and hypoxic conditions, using RNAseq technology. Lipids significantly induced the expression of 368 genes. A main core lipid response was observed involving efflux systems, iron caption and sulfur reduction. In co-expression with ncRNAs and other genes discussed below, may act coordinately to prepare the machinery conferring drug tolerance and increasing a persistent population. Our findings could be useful to tag relevant pathways for the development of new drugs, vaccines and new strategies to control TB. Three in vitro experimental conditions of Mycobacterium tuberculosis H37Rv were evaluated: exponential phase, stationary phase and hypoxic stage NRP1, each assay was tested in lipid conditions as treatment and in presence of dextrose as control. All samples had a biological replicate, yielding a total of 12 experimental samples.