title: Coelomycin, a highly substituted 2,6-dioxo-pyrazine fungal metabolite antibacterial agent discovered by Staphylococcus aureus fitness test profiling.
abstract: Bacterial resistance to antibiotics, particularly to multiple antibiotics, is becoming a cause for significant concern. The only really viable course of action to counter this is to discover new antibiotics with novel modes of action. We have recently implemented a new antisense-based chemical genetic screening technology to accomplish this goal. The discovery and antibacterial activity of coelomycin, a fully substituted 2,6-dioxo pyrazine, illustrates the application of the Staphylococcus aureus fitness test strategy to natural products discovery.
authors.affiliation: Merck Research Laboratories, Rahway, NJ 07065, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Goetz
authors.forename: Chaowei
authors.initials: C
authors.lastname: Zhang
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Zink
authors.forename: Marta
authors.initials: M
authors.lastname: Arocho
authors.forename: Francisca
authors.initials: F
authors.lastname: Vicente
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Bills
authors.forename: Jon
authors.initials: J
authors.lastname: Polishook
authors.forename: Karen
authors.initials: K
authors.lastname: Dorso
authors.forename: Russell
authors.initials: R
authors.lastname: Onishi
authors.forename: Charles
authors.initials: C
authors.lastname: Gill
authors.forename: Emily
authors.initials: E
authors.lastname: Hickey
authors.forename: Suzy
authors.initials: S
authors.lastname: Lee
authors.forename: Richard
authors.initials: R
authors.lastname: Ball
authors.forename: Stephen
authors.initials: S
authors.lastname: Skwish
authors.forename: Robert G K
authors.initials: RG
authors.lastname: Donald
authors.forename: John W
authors.initials: JW
authors.lastname: Phillips
authors.forename: Sheo B
authors.initials: SB
authors.lastname: Singh
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D001203:Ascomycota / Q000302:isolation & purification / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D018653:Juniperus / Q000382:microbiology; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011719:Pyrazines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology*
chemical_list: D000900:Anti-Bacterial Agents; D011719:Pyrazines