Glutathione Provides a Source of Cysteine Essential for Intracellular Multiplication of Francisella tularensis

被引:107
作者
Alkhuder, Khaled [1 ,2 ]
Meibom, Karin L. [1 ,2 ]
Dubail, Iharilalao [1 ,2 ]
Dupuis, Marion [1 ,2 ]
Charbit, Alain [1 ,2 ]
机构
[1] Univ Paris 05, Fac Med Necker Enfants Malades, Paris, France
[2] INSERM, Unite Pathogenie Infect System, U570, Paris, France
关键词
GAMMA-GLUTAMYL-TRANSPEPTIDASE; LIPOPOLYSACCHARIDE O-ANTIGEN; ESCHERICHIA-COLI K-12; MACROPHAGE CELL-LINE; HELICOBACTER-PYLORI; PATHOGENICITY ISLAND; LISTERIA-MONOCYTOGENES; GENE-EXPRESSION; EXTRACELLULAR GLUTATHIONE; VIRULENCE DETERMINANTS;
D O I
10.1371/journal.ppat.1000284
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Francisella tularensis is a highly infectious bacterium causing the zoonotic disease tularemia. Its ability to multiply and survive in macrophages is critical for its virulence. By screening a bank of HimarFT transposon mutants of the F. tularensis live vaccine strain (LVS) to isolate intracellular growth-deficient mutants, we selected one mutant in a gene encoding a putative gamma-glutamyl transpeptidase (GGT). This gene (FTL_0766) was hence designated ggt. The mutant strain showed impaired intracellular multiplication and was strongly attenuated for virulence in mice. Here we present evidence that the GGT activity of F. tularensis allows utilization of glutathione (GSH, gamma-glutamyl-cysteinyl-glycine) and gamma-glutamyl-cysteine dipeptide as cysteine sources to ensure intracellular growth. This is the first demonstration of the essential role of a nutrient acquisition system in the intracellular multiplication of F. tularensis. GSH is the most abundant source of cysteine in the host cytosol. Thus, the capacity this intracellular bacterial pathogen has evolved to utilize the available GSH, as a source of cysteine in the host cytosol, constitutes a paradigm of bacteria-host adaptation.
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页数:11
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