Thursday, August 28, 2014

Focus on: Novel tuberculosis treatments

Tuberculosis (TB) is a widely prevalent disease, causing millions of deaths across the world. Although it is treatable, this is difficult and requires administration of multiple antibiotics. There has recently been a growing problem associated with the appearance of resistant strains. There is also a growing problem of tuberculosis amongst cattle in the UK, with the recent badger cull an attempt to address the transmission of TB to cattle.

Scanning electron micrograph of Mycobacterium
bacteria, which cause TB

One of the traditional classes of antibiotics known as caprazamycins target the enzyme MraY, which is involved in the production of peptidoglycans, an integral part of the bacterial cell wall. Some caprazamycin resistant strains are known to overexpress MraY, making MraY expression and activity an important area of research. A recent research paper published in the Journal of Biological Chemistry 1 describes an approach where a caprazamycin derivative was created that is effective against strains overexpressing MraY as it targets WecA, an enzyme involved in the synthesis of an integral part of the cell wall structure. WecA could therefore be a promising novel target for a new class of antibiotics in the fight against antibiotic resistant strains of Tuberculosis.

In addition, BMG LABTECH recently released an application note for a FRET screening approach to identify modulators of MraY activity entitled: A high-throughput, homogeneous, FRET-based assay to detect bacterial membrane-bound enzyme (MraY) activity

  1. Y. Ishizaki, et al 'Inhibition of the First Step in Synthesis of the Mycobacterial Cell Wall Core, Catalyzed by the GlcN Ac-1-phosphate Transferase WecA, by the Novel Caprazymycin Derivative CPZEN-45' J. Biol. Chem 2013, 288:30309-30319