A critical role of mevalonate for peptidoglycan synthesis in Staphylococcus aureus

Yasuhiko Matsumoto, Jyunichiro Yasukawa, Masaki Ishii, Yohei Hayashi, Shinya Miyazaki, Kazuhisa Sekimizu

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase, a mevalonate synthetase, is required for the growth of Staphylococcus aureus. However, the essential role of the enzyme in cell growth has remained unclear. Here we show that three mutants possessed single-base substitutions in the mvaA gene, which encodes HMG-CoA reductase, show a temperature-sensitive phenotype. The phenotype was suppressed by the addition of mevalonate or farnesyl diphosphate, which is a product synthesized from mevalonate. Farnesyl diphosphate is a precursor of undecaprenyl phosphate that is required for peptidoglycan synthesis. The rate of peptidoglycan synthesis was decreased in the mvaA mutants under the non-permissive conditions and the phenotype was suppressed by the addition of mevalonate. HMG-CoA reductase activities of mutant MvaA proteins in the temperature sensitive mutants were lower than that of wild-type MvaA protein. Our findings from genetic and biochemical analyses suggest that mevalonate produced by HMG-CoA reductase is required for peptidoglycan synthesis for S. aureus cell growth.

Original languageEnglish
Article number22894
JournalScientific reports
Volume6
DOIs
Publication statusPublished - 2016 Mar 10
Externally publishedYes

ASJC Scopus subject areas

  • General

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