title: Transcription of genes involved in sulfolipid and polyacyltrehalose biosynthesis of Mycobacterium tuberculosis in experimental latent tuberculosis infection.
abstract: The Influence of trehalose-based glycolipids in the virulence of Mycobacterium tuberculosis (Mtb) 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 Mtb. 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 Mtb grown in the NRP2 stage. A striking decrease in the transcription of mmpL8 and mmpL10 transporter genes and increased transcription of the pks (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.
authors.affiliation: Departamento de Química, Facultad de Ciencias, Universidad Nacional de Colombia, Bogotá, Colombia.
authors.forename: Jimmy E
authors.initials: JE
authors.lastname: Rodríguez
authors.forename: Ana S
authors.initials: AS
authors.lastname: Ramírez
authors.forename: Laura P
authors.initials: LP
authors.lastname: Salas
authors.forename: Cecilia
authors.initials: C
authors.lastname: Helguera-Repetto
authors.forename: Jorge
authors.initials: J
authors.lastname: Gonzalez-y-Merchand
authors.forename: Carlos Y
authors.initials: CY
authors.lastname: Soto
authors.forename: Rogelio
authors.initials: R
authors.lastname: Hernández-Pando
mesh_terms: D000818:Animals; D002473:Cell Wall / Q000378:metabolism; D002855:Chromatography, Thin Layer; D004195:Disease Models, Animal; D018450:Disease Progression; D005786:Gene Expression Regulation; D015964:Gene Expression Regulation, Bacterial; D008055:Lipids / Q000096:biosynthesis*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D048630:Polyketide Synthases / Q000235:genetics; D012336:RNA, Ribosomal, 16S / Q000378:metabolism; D014199:Trehalose / Q000096:biosynthesis*; D014397:Tuberculosis, Pulmonary / Q000382:microbiology*
chemical_list: D008055:Lipids; D008565:Membrane Proteins; C487808:MmpL8 protein, Mycobacterium tuberculosis; D012336:RNA, Ribosomal, 16S; C015518:sulfolipids; D048630:Polyketide Synthases; D014199:Trehalose; D010100:Oxygen