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Alanine dehydrogenases in mycobacteria.

Ji-A Jeong1, Jeong-Il Oh2

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|February 2, 2019
PubMed
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L-alanine dehydrogenase (Ald) is crucial for Mycobacterium tuberculosis survival under stress by managing nutrient and energy balance. Ald inhibitors show potential when combined with existing tuberculosis drugs.

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Area of Science:

  • Biochemistry
  • Microbiology
  • Enzymology

Background:

  • L-alanine dehydrogenase (Ald) is a key antigen in Mycobacterium tuberculosis.
  • Ald catalyzes the pyruvate-to-alanine conversion, impacting NADH/NAD+ homeostasis.
  • Ald gene expression is upregulated by alanine and under respiration-inhibitory conditions.

Purpose of the Study:

  • To investigate the role of Ald in mycobacterial survival.
  • To understand the regulation of Ald expression.
  • To explore Ald as a therapeutic target for tuberculosis.

Main Methods:

  • Gene expression analysis in Mycobacterium tuberculosis and Mycobacterium smegmatis.
  • Biochemical characterization of Ald enzyme activity.
  • Investigated AldR transcriptional regulator function.

Main Results:

  • Ald expression is upregulated by alanine and stress conditions (oxygen limitation, nutrient starvation).
  • AldR mediates the upregulation of ald genes.
  • Mycobacterial Alds are essential for alanine utilization and survival under stress.
  • Ald inhibitors have been developed and show potential in combination therapy.

Conclusions:

  • Ald plays a vital role in mycobacterial adaptation and survival.
  • AldR is a key regulator of Ald expression.
  • Ald is a promising target for novel anti-tubercular strategies, particularly in combination therapy.