title: A critical role of mevalonate for peptidoglycan synthesis in Staphylococcus aureus.
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.
authors.affiliation: Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 111-0033, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Matsumoto
authors.affiliation: Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 111-0033, Japan.
authors.forename: Jyunichiro
authors.initials: J
authors.lastname: Yasukawa
authors.affiliation: Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 111-0033, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Ishii
authors.affiliation: Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 111-0033, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Hayashi
authors.affiliation: Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 111-0033, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Miyazaki
authors.affiliation: Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 111-0033, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Sekimizu
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D004795:Enzyme Stability / Q000235:genetics; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics* / Q000378:metabolism; D008798:Mevalonic Acid / Q000378:metabolism* / Q000494:pharmacology; D010457:Peptidoglycan / Q000096:biosynthesis* / Q000235:genetics; D011106:Polyisoprenyl Phosphates / Q000494:pharmacology; D012717:Sesquiterpenes / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000235:genetics* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity; D013696:Temperature
chemical_list: D010457:Peptidoglycan; D011106:Polyisoprenyl Phosphates; D012717:Sesquiterpenes; C004808:farnesyl pyrophosphate; D006903:Hydroxymethylglutaryl CoA Reductases; D008798:Mevalonic Acid