title: Streptococcus pneumoniae uses glutathione to defend against oxidative stress and metal ion toxicity.
abstract: The thiol-containing tripeptide glutathione is an important cellular constituent of many eukaryotic and prokaryotic cells. In addition to its disulfide reductase activity, glutathione is known to protect cells from many forms of physiological stress. This report represents the first investigation into the role of glutathione in the Gram-positive pathogen Streptococcus pneumoniae. We demonstrate that pneumococci import extracellular glutathione using the ABC transporter substrate binding protein GshT. Mutation of gshT and the gene encoding glutathione reductase (gor) increases pneumococcal sensitivity to the superoxide generating compound paraquat, illustrating the importance of glutathione utilization in pneumococcal oxidative stress resistance. In addition, the gshT and gor mutant strains are hypersensitive to challenge with the divalent metal ions copper, cadmium, and zinc. The importance of glutathione utilization in pneumococcal colonization and invasion of the host is demonstrated by the attenuated phenotype of the gshT mutant strain in a mouse model of infection.
authors.affiliation: Research Centre for Infectious Diseases, School of Molecular and Biomedical Science, University of Adelaide, South Australia, Australia.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Potter
authors.forename: Claudia
authors.initials: C
authors.lastname: Trappetti
authors.forename: James C
authors.initials: JC
authors.lastname: Paton
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D005980:Glutathione Reductase / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D008670:Metals / Q000494:pharmacology*; D051379:Mice; D009154:Mutation; D018384:Oxidative Stress; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000378:metabolism*; D013997:Time Factors
chemical_list: D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D008670:Metals; C086860:glutathione transporter; D005980:Glutathione Reductase