title: Shigatoxin encoding Bacteriophage ϕ24Bmodulates bacterial metabolism to raise antimicrobial tolerance.
abstract: How temperate bacteriophages play a role in microbial infection and disease progression is not fully understood. They do this in part by carrying genes that promote positive evolutionary selection for the lysogen. Using Biolog phenotype microarrays and comparative metabolite profiling we demonstrate the impact of the well-characterised Shiga toxin-prophage ϕ24Bon its Escherichia coli host MC1061. As a lysogen, the prophage alters the bacterial physiology by increasing the rates of respiration and cell proliferation. This is the first reported study detailing phage-mediated control of the E. coli biotin and fatty acid synthesis that is rate limiting to cell growth. Through ϕ24Bconversion the lysogen also gains increased antimicrobial tolerance to chloroxylenol and 8-hydroxyquinoline. Distinct metabolite profiles discriminate between MC1061 and the ϕ24Blysogen in standard culture, and when treated with 2 antimicrobials. This is also the first reported use of metabolite profiling to characterise the physiological impact of lysogeny under antimicrobial pressure. We propose that temperate phages do not need to carry antimicrobial resistance genes to play a significant role in tolerance to antimicrobials.
authors.affiliation: Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, UK.
authors.forename: G S
authors.initials: GS
authors.lastname: Holt
authors.affiliation: Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, UK.
authors.forename: J K
authors.initials: JK
authors.lastname: Lodge
authors.affiliation: Microbiology Research Group, Institute of Integrative Biology, University of Liverpool, Liverpool, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: McCarthy
authors.affiliation: Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, UK.
authors.forename: A K
authors.initials: AK
authors.lastname: Graham
authors.affiliation: Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, UK.
authors.forename: G
authors.initials: G
authors.lastname: Young
authors.affiliation: Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, UK.
authors.forename: S H
authors.initials: SH
authors.lastname: Bridge
authors.affiliation: School of Medicine, Pharmacy and Health, Durham University, Durham, UK.
authors.forename: A K
authors.initials: AK
authors.lastname: Brown
authors.affiliation: Microbiology Research Group, Institute of Integrative Biology, University of Liverpool, Liverpool, UK.
authors.forename: M
authors.initials: M
authors.lastname: Veses-Garcia
authors.affiliation: Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, UK.
authors.forename: C V
authors.initials: CV
authors.lastname: Lanyon
authors.affiliation: Public Health England, Royal Victoria Hospital, Newcastle upon Tyne, UK.
authors.forename: A
authors.initials: A
authors.lastname: Sails
authors.affiliation: Microbiology Research Group, Institute of Integrative Biology, University of Liverpool, Liverpool, UK.
authors.forename: H E
authors.initials: HE
authors.lastname: Allison
authors.affiliation: Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, UK.
authors.forename: D L
authors.initials: DL
authors.lastname: Smith
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D019540:Area Under Curve; D001435:Bacteriophages / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D016002:Discriminant Analysis; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D007613:Kanamycin Resistance / Q000187:drug effects; D008242:Lysogeny / Q000187:drug effects; D055432:Metabolomics; D015999:Multivariate Analysis; D009997:Osmotic Pressure; D015125:Oxyquinoline / Q000494:pharmacology; D022621:Shiga Toxin / Q000378:metabolism*; D014992:Xylenes / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D014992:Xylenes; C007027:chloroxylenol; D015125:Oxyquinoline; D022621:Shiga Toxin