PDIM and SL1 accumulation in Mycobacterium tuberculosis is associated with mce4A expression

Pooja Singh, Rajesh Sinha, Gaurav Tyagi, Naresh Kumar Sharma, Neeraj K. Saini, Amita Chandolia, Ashok Kumar Prasad, Mandira Varma-Basil, Mridula Bose

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Lipid metabolism forms the heart and soul of Mycobacterium tuberculosis life cycle. Starting from macrophage invasion at cholesterol rich micro-domains to a sustainable survival for infection by utilizing cholesterol, Mycobacterium displays the nexus of metabolic pathways around host derived lipids. mce4 operon acts as cholesterol import system in M. tuberculosis and here we demonstrate role of mce4A gene of this operon in cholesterol catabolism. Here M. tuberculosis H37Rv overexpressing Rv3499c (mce4A) recombinant was used as a model to decipher the metabolic flux during intake and utilization of host lipids by mycobacteria. We analysed the impact of mce4A expression on carbon shift initiated during cholesterol utilization necessary for long term survival of mycobacterium. Through transcriptional analysis, upregulation in methylcitrate cycle (MCC) and methylmalonyl pathway (MMP) genes was observed in Rv3499c overexpressing recombinants of M. tuberculosis H37Rv. Up-regulation of methylmalonyl pathway associated enzyme encoding genes increased accumulation of virulence associated mycobacterial lipids phthiocerol dimycocerates (PDIM) and sulfolipid (SL1). We demonstrate that MCC and MMP associated enzyme encoding genes are upregulated upon mce4A overexpression and lead to enhanced accumulation of PDIM and SL1 which are responsible for pathogenicity of M. tuberculosis.

Original languageEnglish (US)
Pages (from-to)178-187
Number of pages10
JournalGene
Volume642
DOIs
StatePublished - Feb 5 2018

Keywords

  • Cholesterol
  • mce4A
  • Methylcitrate cycle
  • Methylmalonyl pathway
  • String
  • Vitamin B

ASJC Scopus subject areas

  • Genetics

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    Singh, P., Sinha, R., Tyagi, G., Sharma, N. K., Saini, N. K., Chandolia, A., Prasad, A. K., Varma-Basil, M., & Bose, M. (2018). PDIM and SL1 accumulation in Mycobacterium tuberculosis is associated with mce4A expression. Gene, 642, 178-187. https://doi.org/10.1016/j.gene.2017.09.062