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- Title
Roles of rel<sub> Spn</sub> in stringent response, global regulation and virulence of serotype 2 Streptococcus pneumoniae D39.
- Authors
Kazmierczak, Krystyna M.; Wayne, Kyle J.; Rechtsteiner, Andreas; Winkler, Malcolm E.
- Abstract
RelA/SpoT homologue (RSH) proteins have (p)ppGpp synthetase and hydrolase activities that mediate major global responses to nutrient limitation and other stresses. RSH proteins are conserved in most bacteria and play diverse roles in bacterial pathogenesis. We report here that the RSH protein of Streptococcus pneumoniae, Rel Spn, can be deleted and is the primary source of (p)ppGpp synthesis in virulent strain D39 under some conditions. A D39 Δ rel Spn mutant grew well in complex medium, but did not grow in chemically defined medium unless supplemented with the metals copper and manganese. Transcriptome analysis of D39 rel+ Spn and Δ rel Spn strains treated with mupirocin revealed rel Spn-independent (translation stress), rel Spn-dependent (stringent response) and Δ rel Spn-dependent changes, suggesting that rel Spn and (p)ppGpp amount play wide-ranging homeostatic roles in pneumococcal physiology, besides adjusting macromolecular synthesis and transport in response to nutrient availability. Notably, the rel Spn -dependent response included significant upregulation of the ply operon encoding pneumolysin toxin, whereas the Δ rel Spn-dependent response affected expression linked to the VicRK and CiaRH two-component systems. Finally, a D39 Δ rel Spn mutant was severely attenuated and displayed a significantly altered course of disease progression in a mouse model of infection, which was restored to normal by an ectopic copy of rel+ Spn.
- Publication
Molecular Microbiology, 2009, Vol 72, Issue 3, p590
- ISSN
0950-382X
- Publication type
Academic Journal
- DOI
10.1111/j.1365-2958.2009.06669.x