title: Metabonomics-based analysis of Brachyspira pilosicoli's response to tiamulin reveals metabolic activity despite significant growth inhibition.
abstract: Pathogenic anaerobes Brachyspira spp. are responsible for an increasing number of Intestinal Spirochaetosis (IS) cases in livestock against which few approved treatments are available. Tiamulin is used to treat swine dysentery caused by Brachyspira spp. and recently has been used to handle avian intestinal spirochaetosis (AIS). The therapeutic dose used in chickens requires further evaluation since cases of bacterial resistance to tiamulin have been reported. In this study, we evaluated the impact of tiamulin at varying concentrations on the metabolism of B. pilosicoli using a1H-NMR-based metabonomics approach allowing the capture of the overall bacterial metabolic response to antibiotic treatment. Based on growth curve studies, tiamulin impacted bacterial growth even at very low concentration (0.008 μg/mL) although its metabolic activity was barely affected 72 h post exposure to antibiotic treatment. Only the highest dose of tiamulin tested (0.250 μg/mL) caused a major metabolic shift. Results showed that below this concentration, bacteria could maintain a normal metabolic trajectory despite significant growth inhibition by the antibiotic, which may contribute to disease reemergence post antibiotic treatment. Indeed, we confirmed that B. pilosicoli remained viable even after exposition to the highest antibiotic dose. This paper stresses the need to ensure new evaluation of bacterial viability post bacteriostatic exposure such as tiamulin to guarantee treatment efficacy and decrease antibiotic resistance development.
authors.affiliation: Department of Food and Nutritional Sciences, University of Reading, Whiteknights, Reading, UK6 6AP, UK.
authors.forename: Caroline Ivanne
authors.initials: CI
authors.lastname: Le Roy
authors.affiliation: Faculty of Health and Medical Sciences, School of Veterinary Medicine, University of Surrey, Guilford, Surrey GU2 7XH, UK.
authors.forename: Jade Louise
authors.initials: JL
authors.lastname: Passey
authors.affiliation: Department of Food and Nutritional Sciences, University of Reading, Whiteknights, Reading, UK6 6AP, UK.
authors.forename: Martin John
authors.initials: MJ
authors.lastname: Woodward
authors.affiliation: Faculty of Health and Medical Sciences, School of Veterinary Medicine, University of Surrey, Guilford, Surrey GU2 7XH, UK.
authors.forename: Roberto Marcello
authors.initials: RM
authors.lastname: La Ragione
authors.affiliation: Department of Food and Nutritional Sciences, University of Reading, Whiteknights, Reading, UK6 6AP, UK. Electronic address: s.p.claus@reading.ac.uk.
authors.forename: Sandrine Paule
authors.initials: SP
authors.lastname: Claus
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017400:Brachyspira / Q000737:chemistry* / Q000187:drug effects* / Q000254:growth & development; D004224:Diterpenes / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D055432:Metabolomics
chemical_list: D000900:Anti-Bacterial Agents; D004224:Diterpenes; C014224:tiamulin
keywords: Antibiotics; Brachyspira pilosicoli; Metabonomics; Tiamulin