glpx Gene in Mycobacterium... Vivo Survival.PDF (1.31 MB)
0/0

Glpx gene in mycobacterium tuberculosis is required for in vitro gluconeogenic growth and in vivo survival

Download (1.31 MB)
journal contribution
posted on 29.08.2016 by H. J. Gutka, Y. Wang, S. G. Franzblau, F. Movahedzadeh
Several enzymes involved in central carbon metabolism and gluconeogenesisplay a critical role in survival and pathogenesis of Mycobacterium tuberculosis (Mtb). The only known functional fructose 1,6-bisphosphatase (FBPase) in Mtb is encoded by the glpX gene and belongs to the Class II sub-family of FBPase. We describe herein the generation of a ΔglpX strain using homologous recombination. Although the growth profile of ΔglpX is comparable to that of wild type Mtb when grown on the standard enrichment media, its growth is dysgonic with individual gluconeogenic substrates such as oleic acid, glycerol and acetate. In mice lung CFU titers of ΔglpX were 2-3 log10 lower than the wild-type Mtb strain. The results indicate that glpX gene encodes a functional FBPase and is essential for both in vitro and in vivo growth and survival of Mtb. Loss of glpX results in significant reduction of FBPase activity but not complete abolition. These findings verify that the glpX encoded FBPase II in Mtb can be a potential target for drug discovery.

Funding

This work was supported by the American Lung Association (Grant No. RG-82534-N), and the Chicago Biomedical Consortium with support from The Searle Funds at the Chicago Community Trust.

History

Publisher Statement

This is a copy of an article published in the PLoS ONE. © 2015 Gutka et al.

Publisher

Public Library of Science

Language

en_US

issn

1932-6203

Issue date

23/09/2015

Exports

Categories

Exports