Mycobacterium tuberculosis requires glyoxylate shunt and reverse methylcitrate cycle for lactate and pyruvate metabolism.

Molecular Microbiology
Agnese SerafiniLuiz Pedro S de Carvalho

Abstract

Bacterial nutrition is an essential aspect of host-pathogen interaction. For the intracellular pathogen Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis in humans, fatty acids derived from lipid droplets are considered the major carbon source. However, many other soluble nutrients are available inside host cells and may be used as alternative carbon sources. Lactate and pyruvate are abundant in human cells and fluids, particularly during inflammation. In this work, we study Mtb metabolism of lactate and pyruvate combining classic microbial physiology with a 'multi-omics' approach consisting of transposon-directed insertion site sequencing (TraDIS), RNA-seq transcriptomics, proteomics and stable isotopic labelling coupled with mass spectrometry-based metabolomics. We discovered that Mtb is well adapted to use both lactate and pyruvate and that their metabolism requires gluconeogenesis, valine metabolism, the Krebs cycle, the GABA shunt, the glyoxylate shunt and the methylcitrate cycle. The last two pathways are traditionally associated with fatty acid metabolism and, unexpectedly, we found that in Mtb the methylcitrate cycle operates in reverse, to allow optimal metabolism of lactate and pyruvate. Our findin...Continue Reading

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Citations

Jan 11, 2020·Frontiers in Immunology·Andreu Garcia-VilanovaJordi B Torrelles
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Methods Mentioned

BETA
PCR
Protein Assay
Illumina sequencing

Software Mentioned

Bowtie
DESeq2
Rsamtools
pheatmap
TraDIS
Bowtie2
samtools bedcov
R R
MaxQuant
Perseus

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