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

PLoS Pathogens

Karin L. Meibom¹  Marion Dupuis¹  Alain Charbit²  Khaled Alkhuder²  Iharilalao Dubail² 

[1] INSERM, U570, Unité de Pathogénie des Infections Systémiques, Paris, France;Université Paris Descartes, Faculté de Médecine Necker-Enfants Malades, Paris, France

关键词: Cysteine;    Francisella tularensis;    Intracellular pathogens;    Macrophages;    Bacterial pathogens;    Glutathione;    Bacterial diseases;    Chocolate;   

DOI  :  10.1371/journal.ppat.1000284

学科分类：生物科学（综合）

来源: Public Library of Science

【 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 γ-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, γ-glutamyl-cysteinyl-glycine) and γ-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.

【 授权许可】

CC BY