Oxidative Stress and Metal Ion Toxicity

15 16 The thiol-containing tripeptide glutathione is an important cellular constituent of many 17 eukaryotic and prokaryotic cells. In addition to its disulfide reductase activity, 18 glutathione is known to protect cells from many forms of physiological stress. This 19 report represents the first investigation into the role of glutathione in the Gram-positive 20 pathogen, Streptococcus pneumoniae. We demonstrate that pneumococci import 21 extracellular glutathione using the ABC transporter substrate binding protein GshT. 22 Mutation of gshT and the gene encoding glutathione reductase (gor) increases 23 pneumococcal sensitivity to the superoxide generating compound paraquat, illustrating 24 the importance of glutathione utilisation in pneumococcal oxidative stress resistance. In 25 addition, the gshT and gor mutant strains are hyper-sensitive to challenge with the 26 divalent metal ions copper, cadmium and zinc. The importance of glutathione utilisation 27 in pneumococcal colonisation and invasion of the host is demonstrated by the 28 attenuated phenotype of the gshT mutant strain in a mouse model of infection. 29 30 on July 3, 2017 by gest http/jb.asm .rg/ D ow nladed fom