The (p)ppGpp synthetase RelA contributes to stress adaptation and virulence in Enterococcus faecalis V583
Yan, Xue and Zhao, Chen and Budin-Verneuil, Aurélie and Hartke, Axel and Rincé, Alain and Gilmore, Michael S. and Auffray, Yanick and Pichereau, Vianney,, 155, 3226-3237 (2009),
doi = https://doi.org/10.1099/mic.0.026146-0,
publicationName = Microbiology Society,
issn = 1350-0872,
abstract= Guanosine penta- and tetraphosphate [(p)ppGpp] are two unusual nucleotides implied in the bacterial stringent response. In many pathogenic bacteria, mutants unable to synthesize these molecules lose their virulence. In Gram-positive bacteria such as Enterococcus faecalis, the synthesis and degradation of (p)ppGpp mainly depend on the activity of a bifunctional enzyme, encoded by the relA gene. By analysing ΔrelA and ΔrelQ (which encodes a protein harbouring a ppGpp synthetase activity) deletion mutants, we showed that RelA is by far the main system leading to (p)ppGpp production under our experimental conditions, and during the development of a stringent response induced by mupirocin. We also constructed a mutant (ΔrelAsp) in which a small part of the relA gene (about 0.7 kbp) encoding the carboxy-terminal domain of the RelA protein was deleted. Both relA mutants were more resistant than the wild-type strain to 0.3 % bile salts, 25 % ethanol and acid (pH 2.3) challenges. Interestingly, the ΔrelAsp mutant grew better than the two other strains in the presence of 1 mM H2O2, but did not display increased tolerance when subjected to lethal doses of H2O2 (45 mM). By contrast, the ΔrelA mutant was highly sensitive to 45 mM H2O2 and displayed reduced growth in a medium containing 1 M NaCl. The two mutants also displayed contrasting virulence phenotypes towards larvae of the Greater Wax Moth infection model Galleria mellonella. Indeed, although the ΔrelA mutant did not display any phenotype, the ΔrelAsp mutant was more virulent than the wild-type strain. This virulent phenotype should stem from its increased ability to proliferate under oxidative environments.,
language=,
type=