title: Avian pathogenic Escherichia coli ΔtonB mutants are safe and protective live-attenuated vaccine candidates.
abstract: Avian pathogenic Escherichia coli (APEC) cause colibacillosis, a serious respiratory disease in poultry. Most APEC strains possess TonB-dependent outer membrane transporters for the siderophores salmochelin and aerobactin, which both contribute to their capacity to cause disease. To assess the potential of iron transport deficient mutants as vaccine candidates, the tonB gene was deleted in the APEC wild type strain E956 and a Δfur (ferric uptake repressor) mutant of E956. The growth of the ΔtonB and ΔtonB/Δfur mutants was impaired in iron-restricted conditions, but not in iron-replete media. Day old chicks were exposed to aerosols of the mutants to assess their efficacy as live attenuated vaccines. At day 18, the birds were challenged with aerosols of the virulent parent strain E956. Both mutants conferred protection against colibacillosis; weight gains and lesion scores were significantly different between the vaccinated groups and an unvaccinated challenged control group. Thus mutation of iron uptake systems can be used as a platform technology to generate protective live attenuated vaccines against extraintestinal E. coli infections, and potentially a range of Gram negative pathogens of importance in veterinary medicine.
authors.affiliation: Asia-Pacific Centre for Animal Health, Faculty of Veterinary Science, The University of Melbourne, 250 Princes Hwy, Werribee, VIC 3030, Australia. Electronic address: karen.holden@csiro.au.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Holden
authors.affiliation: Asia-Pacific Centre for Animal Health, Faculty of Veterinary Science, The University of Melbourne, Cnr Flemington Road and Park Drive, Parkville, VIC 3052, Australia.
authors.forename: Glenn F
authors.initials: GF
authors.lastname: Browning
authors.affiliation: Asia-Pacific Centre for Animal Health, Faculty of Veterinary Science, The University of Melbourne, 250 Princes Hwy, Werribee, VIC 3030, Australia.
authors.forename: Amir H
authors.initials: AH
authors.lastname: Noormohammadi
authors.affiliation: Asia-Pacific Centre for Animal Health, Faculty of Veterinary Science, The University of Melbourne, Cnr Flemington Road and Park Drive, Parkville, VIC 3052, Australia.
authors.forename: Philip
authors.initials: P
authors.lastname: Markham
authors.affiliation: Asia-Pacific Centre for Animal Health, Faculty of Veterinary Science, The University of Melbourne, 250 Princes Hwy, Werribee, VIC 3030, Australia. Electronic address: mmarenda@unimelb.edu.au.
authors.forename: Marc S
authors.initials: MS
authors.lastname: Marenda
mesh_terms: D015082:2,2'-Dipyridyl; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D002645:Chickens; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics / Q000276:immunology*; D004927:Escherichia coli Infections / Q000276:immunology / Q000662:veterinary*; D029968:Escherichia coli Proteins / Q000235:genetics*; D022361:Escherichia coli Vaccines / Q000235:genetics / Q000276:immunology*; D007501:Iron / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics*; D016296:Mutagenesis; D009154:Mutation / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000662:veterinary; D011201:Poultry Diseases / Q000276:immunology* / Q000382:microbiology*; D012097:Repressor Proteins / Q000235:genetics; D014613:Vaccines, Attenuated / Q000276:immunology
chemical_list: D001426:Bacterial Proteins; D017931:DNA Primers; D029968:Escherichia coli Proteins; D022361:Escherichia coli Vaccines; D008565:Membrane Proteins; D012097:Repressor Proteins; D014613:Vaccines, Attenuated; C068477:ferric uptake regulating proteins, bacterial; C489181:tonB protein, E coli; D015082:2,2'-Dipyridyl; D007501:Iron
keywords: Avian colibacillosis; Live vaccine; Siderophore transporter; TonB