Maltose-1-Phosphate Stress Stimulon in Mycobacterium tuberculosis

ABSTRACT: New chemotherapeutics are urgently required to control the tuberculosis pandemic fueled by the emergence of multidrug- and extensively-drug-resistant Mycobacterium tuberculosis strains and the bacterium`s catastrophic alliance with HIV. Here we describe a novel trehalose-to-α-glucan pathway in M. tuberculosis comprising four enzymatic steps mediated by TreS, Pep2, GlgB, and GlgE, identified as an essential maltosyltransferase capable of utilizing maltose 1-phosphate. Using traditional and chemical reverse genetics, we show that GlgE inactivation causes rapid death of M. tuberculosis in vitro and in mice, through self-poisoning by maltose 1-phosphate accumulation driven by a self-amplifying feedback loop promoting pleiotropic phosphosugar-induced stress responses. Moreover, this α-glucan

ORGANISM(S): Mycobacterium tuberculosis

SUBMITTER: Brian Weinrick 

PROVIDER: E-GEOD-18575 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress