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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2010-4-19
pubmed:abstractText
In most bacteria, nutrient limitations provoke the stringent control through the rapid synthesis of the alarmones pppGpp and ppGpp. Little is known about the stringent control in the human pathogen Staphylococcus aureus, partly due to the essentiality of the major (p)ppGpp synthase/hydrolase enzyme RSH (RelA/SpoT homolog). Here, we show that mutants defective only in the synthase domain of RSH (rsh(syn)) are not impaired in growth under nutrient-rich conditions. However, these mutants were more sensitive toward mupirocin and were impaired in survival when essential amino acids were depleted from the medium. RSH is the major enzyme responsible for (p)ppGpp synthesis in response to amino acid deprivation (lack of Leu/Val) or mupirocin treatment. Transcriptional analysis showed that the RSH-dependent stringent control in S. aureus is characterized by repression of genes whose products are predicted to be involved in the translation machinery and by upregulation of genes coding for enzymes involved in amino acid metabolism and transport which are controlled by the repressor CodY. Amino acid starvation also provoked stabilization of the RNAs coding for major virulence regulators, such as SaeRS and SarA, independently of RSH. In an animal model, the rsh(syn) mutant was shown to be less virulent than the wild type. Virulence could be restored by the introduction of a codY mutation into the rsh(syn) mutant. These results indicate that stringent conditions are present during infection and that RSH-dependent derepression of CodY-regulated genes is essential for virulence in S. aureus.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1098-5522
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
78
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1873-83
pubmed:dateRevised
2010-11-2
pubmed:meshHeading
pubmed-meshheading:20212088-Animals, pubmed-meshheading:20212088-Anti-Bacterial Agents, pubmed-meshheading:20212088-Biosynthetic Pathways, pubmed-meshheading:20212088-Colony Count, Microbial, pubmed-meshheading:20212088-Culture Media, pubmed-meshheading:20212088-Female, pubmed-meshheading:20212088-Gene Expression Profiling, pubmed-meshheading:20212088-Gene Expression Regulation, Bacterial, pubmed-meshheading:20212088-Guanosine Pentaphosphate, pubmed-meshheading:20212088-Ligases, pubmed-meshheading:20212088-Mice, pubmed-meshheading:20212088-Mice, Inbred BALB C, pubmed-meshheading:20212088-Microbial Sensitivity Tests, pubmed-meshheading:20212088-Microbial Viability, pubmed-meshheading:20212088-Mupirocin, pubmed-meshheading:20212088-Mutation, pubmed-meshheading:20212088-Staphylococcal Infections, pubmed-meshheading:20212088-Staphylococcus aureus, pubmed-meshheading:20212088-Virulence, pubmed-meshheading:20212088-Virulence Factors
pubmed:year
2010
pubmed:articleTitle
Role of the (p)ppGpp synthase RSH, a RelA/SpoT homolog, in stringent response and virulence of Staphylococcus aureus.
pubmed:affiliation
Interfaculty Institute of Microbiology and Infection Medicine, Universität Tübingen, Elfriede-Aulhorn-Strasse 6, 72076 Tübingen, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't