The significance of GlgE as a new target for tuberculosis

Rainer Kalscheuer, William R. Jacobs

Research output: Contribution to journalReview article

Abstract

Largely neglected by the industrialized world for decades, tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis, has made a fulminant return to the public health agenda as a major global health threat. The worsening of the TB pandemic is driven by the rapid emergence of multidrug-resistant and extensively drug-resistant M. tuberculosis strains, which are virtually untreatable with current chemotherapies. The search for new strategies to combat such resistant strains is of paramount importance for control of the TB pandemic. In searching for new vulnerable processes in M. tuberculosis to enable the rational design of more efficient anti-TB chemotherapy, a novel class of antimycobacterial drug targets has recently been discovered; it is represented by GlgE, an essential maltosyltransferase that elongates linear α-glucans as part of a synthetic lethal biosynthetic pathway. Inactivation of GlgE causes accumulation of a toxic phosphosugar intermediate, maltose 1-phosphate, which drives the bacilli into a suicidal self-poisoning cycle that elicits a complex stress profile, eventually resulting in DNA damage and death of M. tuberculosis. GlgE combines many favorable properties that make it a highly attractive novel drug target for chemotherapy of TB.

Original languageEnglish (US)
Pages (from-to)619-624
Number of pages6
JournalDrug News and Perspectives
Volume23
Issue number10
DOIs
StatePublished - Dec 1 2010

Fingerprint

Extensively Drug-Resistant Tuberculosis
Antitubercular Agents
Glucosyltransferases
Multidrug-Resistant Tuberculosis
Drug Design
Drug Delivery Systems
Mycobacterium tuberculosis
Tuberculosis
Pandemics
Drug Therapy
Glucans
Poisons
Biosynthetic Pathways
Mycobacterium
Pharmaceutical Preparations
Poisoning
Bacillus
DNA Damage
Public Health
Bacteria

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

Cite this

The significance of GlgE as a new target for tuberculosis. / Kalscheuer, Rainer; Jacobs, William R.

In: Drug News and Perspectives, Vol. 23, No. 10, 01.12.2010, p. 619-624.

Research output: Contribution to journalReview article

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