title: HmgR, a key enzyme in the mevalonate pathway for isoprenoid biosynthesis, is essential for growth of Listeria monocytogenes EGDe.
abstract: Isoprenoids may be synthesized via one of two pathways, the classical mevalonate pathway or the alternative 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway. While the majority of bacteria utilize a single pathway for isoprenoid biosynthesis, Listeria monocytogenes is unusual in possessing the complete set of genes for both pathways. Here, we utilized new molecular tools to create precise gene deletions in selected genes encoding enzymes of both pathways, gcpE, lytB (encoding proteins in the MEP pathway) and hmgR (encoding a protein in the mevalonate pathway). We demonstrate that the hmgR gene can only be deleted when the growth medium is supplemented with exogenous mevalonate. Furthermore, full growth of the mutant in the absence of mevalonate was only possible when the intact hmgR gene was supplied in trans using an IPTG-inducible expression system. Murine competitive index assays performed via the oral and intraperitoneal routes of infection revealed that the mevalonate hmgR mutant could not be recovered from livers and spleens 3 days post-infection. We propose that HmgR in L. monocytogenes EGDe is involved in essential metabolic functions and that an intact MEP pathway is not capable of sustaining growth.
authors.affiliation: Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.|Department of Microbiology, University College Cork, Cork, Ireland.
authors.forename: Sinead
authors.initials: S
authors.lastname: Heuston
authors.affiliation: Department of Microbiology, University College Cork, Cork, Ireland.
authors.forename: Máire
authors.initials: M
authors.lastname: Begley
authors.affiliation: Department of Infection, Immunity and Biochemistry, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Martin S
authors.initials: MS
authors.lastname: Davey
authors.affiliation: Department of Infection, Immunity and Biochemistry, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Matthias
authors.initials: M
authors.lastname: Eberl
authors.affiliation: Department of Microbiology, University College Cork, Cork, Ireland.
authors.forename: Pat G
authors.initials: PG
authors.lastname: Casey
authors.affiliation: Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.|Department of Microbiology, University College Cork, Cork, Ireland.
authors.forename: Colin
authors.initials: C
authors.lastname: Hill
authors.affiliation: School of Pharmacy, University College Cork, Cork, Ireland.|Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.|Department of Microbiology, University College Cork, Cork, Ireland.
authors.forename: Cormac G M
authors.initials: CGM
authors.lastname: Gahan
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D053898:Biosynthetic Pathways / Q000235:genetics*; D004195:Disease Models, Animal; D004798:Enzymes / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D005798:Genes, Bacterial; D020043:Genes, Essential; D005816:Genetic Complementation Test; D008089:Listeria monocytogenes / Q000201:enzymology / Q000235:genetics* / Q000254:growth & development*; D008088:Listeriosis / Q000382:microbiology / Q000473:pathology; D008099:Liver / Q000382:microbiology; D008798:Mevalonic Acid / Q000378:metabolism*; D051379:Mice; D013154:Spleen / Q000382:microbiology; D013729:Terpenes / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D004798:Enzymes; D013729:Terpenes; D008798:Mevalonic Acid