Glutathione Provides a Source of Cysteine Essential for Intracellular Multiplication of Francisella tularensis (original) (raw)
Figure 8
A model of utilization of GSH and γ-Glu-Cys by cytosolic F. tularensis.
F. tularensis requires cysteine for growth. It can utilize GSH (and its oxidized form GSSG), γ-Glu-Cys, cysteine, and cystine as sources of cysteine. In eukaryotic host cells, the intracellular concentration of GSH depends on the availability and transport of cystine (oxidized form of cysteine) and cysteine. Cytosolic GSH, the most abundant thiol-containing compound (present in the mM range), and γ-Glu-Cys serve as sources of cysteine for intracellular growth of F. tularensis. In wild-type bacteria, GSH and γ-Glu-Cys are processed by GGT to produce γ-Glu and Cys-Gly or γ-Glu and Cys, respectively. The Cys-Gly dipeptide is further processed by other amino-acid peptidases to produce free cysteine and glycine. GGT-negative bacteria are unable to process these compounds, and the available concentration of free cysteine is too low to promote bacterial growth.