1887

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 , the synthesis and degradation of (p)ppGpp mainly depend on the activity of a bifunctional enzyme, encoded by the gene. By analysing Δ and Δ (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 (Δ) in which a small part of the gene (about 0.7 kbp) encoding the carboxy-terminal domain of the RelA protein was deleted. Both mutants were more resistant than the wild-type strain to 0.3 % bile salts, 25 % ethanol and acid (pH 2.3) challenges. Interestingly, the Δ mutant grew better than the two other strains in the presence of 1 mM HO, but did not display increased tolerance when subjected to lethal doses of HO (45 mM). By contrast, the Δ mutant was highly sensitive to 45 mM HO 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 . Indeed, although the Δ mutant did not display any phenotype, the Δ mutant was more virulent than the wild-type strain. This virulent phenotype should stem from its increased ability to proliferate under oxidative environments.

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2009-10-01
2019-11-14
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