title: Unraveling the structure-activity relationship of tomatidine, a steroid alkaloid with unique antibiotic properties against persistent forms of Staphylococcus aureus.
abstract: Staphylococcus aureus (S. aureus) is responsible for difficult-to-treat and relapsing infections and constitutes one of the most problematic pathogens due to its multiple resistances to clinically available antibiotics. Additionally, the ability of S. aureus to develop small-colony variants is associated with a reduced susceptibility to aminoglycoside antibiotics and in vivo persistence. We have recently demonstrated that tomatidine, a steroid alkaloid isolated from tomato plants, possesses anti-virulence activity against normal strains of S. aureus as well as the ability to potentiate the effect of aminoglycoside antibiotics. In addition, tomatidine has shown antibiotic activity against small-colony variants of S. aureus. We herein report the first study of the structure-activity relationship of tomatidine against S. aureus.
authors.affiliation: Institut de Pharmacologie de Sherbrooke, Département de pharmacologie, Université de Sherbrooke, 3001, 12e av nord, Sherbrooke, Québec J1H 5N4, Canada.
authors.forename: Félix
authors.initials: F
authors.lastname: Chagnon
authors.affiliation: Centre d'étude et de valorisation de la diversité microbienne (CEVDM), Département de biologie, Université de Sherbrooke, Sherbrooke, Québec J1K 2R1, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Guay
authors.affiliation: Institut de Pharmacologie de Sherbrooke, Département de pharmacologie, Université de Sherbrooke, 3001, 12e av nord, Sherbrooke, Québec J1H 5N4, Canada.
authors.forename: Marc-André
authors.initials: MA
authors.lastname: Bonin
authors.affiliation: Centre d'étude et de valorisation de la diversité microbienne (CEVDM), Département de biologie, Université de Sherbrooke, Sherbrooke, Québec J1K 2R1, Canada.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Mitchell
authors.affiliation: Centre d'étude et de valorisation de la diversité microbienne (CEVDM), Département de biologie, Université de Sherbrooke, Sherbrooke, Québec J1K 2R1, Canada.
authors.forename: Kamal
authors.initials: K
authors.lastname: Bouarab
authors.affiliation: Centre d'étude et de valorisation de la diversité microbienne (CEVDM), Département de biologie, Université de Sherbrooke, Sherbrooke, Québec J1K 2R1, Canada.
authors.forename: François
authors.initials: F
authors.lastname: Malouin
authors.affiliation: Institut de Pharmacologie de Sherbrooke, Département de pharmacologie, Université de Sherbrooke, 3001, 12e av nord, Sherbrooke, Québec J1H 5N4, Canada. Electronic address: eric.marsault@usherbrooke.ca.
authors.forename: Éric
authors.initials: É
authors.lastname: Marsault
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development; D013329:Structure-Activity Relationship; D014053:Tomatine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; C003677:tomatidine; D014053:Tomatine
keywords: Aminoglycoside potentiation; Antibiotic; Small colony variants; Staphylococcus aureus; Steroid alkaloid; Structure–activity relationship; Tomatidine