title: A β-lactone-based antivirulence drug ameliorates Staphylococcus aureus skin infections in mice.
abstract: Skin infections caused by Staphylococcus aureus are a major clinical concern, especially if they are caused by multi-resistant strains. In these cases, a spread into deeper soft tissues or the bloodstream results in life-threatening conditions that are difficult to treat by conventional antibiotics. Previous in vitro experiments with a small β-lactone-based molecule demonstrated that antibiotic-sensitive and -resistant S. aureus strains are effectively disarmed in their virulence and corresponding pathogenicity. In this work, in vivo mouse studies show that this methodology is effective for the treatment of skin abscesses in mice. A single dose of the β-lactone significantly decreased abscess size even when applied 6 h post-infection. Although the molecule requires pharmacological optimization (improved stability, for example), this study emphasizes the potential value of antivirulence therapies.
authors.affiliation: AVIRU, EXIST Transfer of Research, OC II, Lichtenbergstraße 4, 85747 Garching (Germany).
authors.forename: Franziska
authors.initials: F
authors.lastname: Weinandy
authors.forename: Katrin
authors.initials: K
authors.lastname: Lorenz-Baath
authors.forename: Vadim S
authors.initials: VS
authors.lastname: Korotkov
authors.forename: Thomas
authors.initials: T
authors.lastname: Böttcher
authors.forename: Shneh
authors.initials: S
authors.lastname: Sethi
authors.forename: Trinad
authors.initials: T
authors.lastname: Chakraborty
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Sieber
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006868:Hydrolysis; D007783:Lactones / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D008826:Microbial Sensitivity Tests; D013207:Staphylococcal Skin Infections / Q000188:drug therapy* / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000472:pathogenicity*; D013329:Structure-Activity Relationship; D014774:Virulence / Q000187:drug effects
chemical_list: D007783:Lactones
keywords: Staphylococcus aureus; antivirulence drugs; caseinolytic protease P; mouse skin infection model; β-lactones