Transcription of Genes Involved in Sulfolipid and Polyacyltrehalose Biosynthesis of <em>Mycobacterium tuberculosis</em> in Experimental Latent Tuberculosis Infection

<div><p>The Influence of trehalose-based glycolipids in the virulence of <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) is recognised; however, the actual role of these cell-wall glycolipids in latent infection is unknown. As an initial approach, we determined by two-dimensional thin-layer chromatography the sulfolipid (SL) and diacyltrehalose/polyacyltrehalose (DAT/PAT) profile of the cell wall of hypoxic <i>Mtb</i>. Then, qRT-PCR was extensively conducted to determine the transcription profile of genes involved in the biosynthesis of these glycolipids in non-replicating persistent 1 (NRP1) and anaerobiosis (NRP2) models of hypoxia (Wayne model), and murine models of chronic and progressive pulmonary tuberculosis. A diminished content of SL and increased amounts of glycolipids with chromatographic profile similar to DAT were detected in <i>Mtb</i> grown in the NRP2 stage. A striking decrease in the transcription of <i>mmpL8</i> and <i>mmpL10</i> transporter genes and increased transcription of the <i>pks</i> (polyketidesynthase) genes involved in SL and DAT biosynthesis were detected in both the NRP2 stage and the murine model of chronic infection. All genes were found to be up-regulated in the progressive disease. These results suggest that SL production is diminished during latent infection and the DAT/PAT precursors can be accumulated inside tubercle bacilli and are possibly used in reactivation processes.</p>