title: A Novel Protective Vaccine Antigen from the CoreEscherichia coliGenome.
abstract: Escherichia coliis a versatile pathogen capable of causing intestinal and extraintestinal infections that result in a huge burden of global human disease. The diversity ofE. coliis reflected by its multiple different pathotypes and mosaic genome composition.E. colistrains are also a major driver of antibiotic resistance, emphasizing the urgent need for new treatment and prevention measures. Here, we used a large data set comprising 1,700 draft and complete genomes to define the core and accessory genome ofE. coliand demonstrated the overlapping relationship between strains from different pathotypes. In combination with proteomic investigation, this analysis revealed core genes that encode surface-exposed or secreted proteins that represent potential broad-coverage vaccine antigens. One of these antigens, YncE, was characterized as a conserved immunogenic antigen able to protect against acute systemic infection in mice after vaccination. Overall, this work provides a genomic blueprint for future analyses of conserved and accessoryE. coligenes. The work also identified YncE as a novel antigen that could be exploited in the development of a vaccine against all pathogenicE. colistrains-an important direction given the high global incidence of infections caused by multidrug-resistant strains for which there are few effective antibiotics.IMPORTANCEE. coliis a multifaceted pathogen of major significance to global human health and an important contributor to increasing antibiotic resistance. Given the paucity of therapies still effective against multidrug-resistant pathogenicE. colistrains, novel treatment and prevention strategies are urgently required. In this study, we defined the core and accessory components of theE. coligenome by examining a large collection of draft and completely sequenced strains available from public databases. This data set was mined by employing a reverse-vaccinology approach in combination with proteomics to identify putative broadly protective vaccine antigens. One such antigen was identified that was highly immunogenic and induced protection in a mouse model of bacteremia. Overall, our study provides a genomic and proteomic framework for the selection of novel vaccine antigens that could mediate broad protection against pathogenicE. coli.
authors.affiliation: School of Chemistry and Molecular Biosciences, the University of Queensland, Queensland, Brisbane, Australia; Australian Infectious Diseases Research Centre, the University of Queensland, Queensland, Brisbane, Australia.
authors.forename: Danilo G
authors.initials: DG
authors.lastname: Moriel
authors.affiliation: School of Chemistry and Molecular Biosciences, the University of Queensland, Queensland, Brisbane, Australia; Australian Infectious Diseases Research Centre, the University of Queensland, Queensland, Brisbane, Australia.
authors.forename: Lendl
authors.initials: L
authors.lastname: Tan
authors.affiliation: School of Chemistry and Molecular Biosciences, the University of Queensland, Queensland, Brisbane, Australia; Australian Infectious Diseases Research Centre, the University of Queensland, Queensland, Brisbane, Australia.
authors.forename: Kelvin G K
authors.initials: KG
authors.lastname: Goh
authors.affiliation: School of Chemistry and Molecular Biosciences, the University of Queensland, Queensland, Brisbane, Australia; Australian Infectious Diseases Research Centre, the University of Queensland, Queensland, Brisbane, Australia.
authors.forename: Minh-Duy
authors.identifier: 0000-0002-3426-1044
authors.initials: MD
authors.lastname: Phan
authors.affiliation: School of Medical Sciences and Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia.
authors.forename: Deepak S
authors.initials: DS
authors.lastname: Ipe
authors.affiliation: School of Chemistry and Molecular Biosciences, the University of Queensland, Queensland, Brisbane, Australia; Australian Infectious Diseases Research Centre, the University of Queensland, Queensland, Brisbane, Australia.
authors.forename: Alvin W
authors.initials: AW
authors.lastname: Lo
authors.affiliation: School of Chemistry and Molecular Biosciences, the University of Queensland, Queensland, Brisbane, Australia; Australian Infectious Diseases Research Centre, the University of Queensland, Queensland, Brisbane, Australia.
authors.forename: Kate M
authors.initials: KM
authors.lastname: Peters
authors.affiliation: School of Medical Sciences and Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia.
authors.forename: Glen C
authors.identifier: 0000-0002-9638-8091
authors.initials: GC
authors.lastname: Ulett
authors.affiliation: School of Chemistry and Molecular Biosciences, the University of Queensland, Queensland, Brisbane, Australia; Australian Infectious Diseases Research Centre, the University of Queensland, Queensland, Brisbane, Australia.
authors.forename: Scott A
authors.identifier: 0000-0002-1806-3283
authors.initials: SA
authors.lastname: Beatson
authors.affiliation: School of Chemistry and Molecular Biosciences, the University of Queensland, Queensland, Brisbane, Australia; Australian Infectious Diseases Research Centre, the University of Queensland, Queensland, Brisbane, Australia.
authors.forename: Mark A
authors.identifier: 0000-0003-4863-9260
authors.initials: MA
authors.lastname: Schembri
keywords: Escherichia coli; vaccines; virulence factors