A Novel Protective Vaccine Antigen from the Core Escherichia coli Genome Danilo G. Moriel, a,b * Lendl Tan, a,b Kelvin G. K. Goh, a,b Minh-Duy Phan, a,b Deepak S. Ipe, c Alvin W. Lo, a,b Kate M. Peters, a,b Glen C. Ulett, c Scott A. Beatson, a,b Mark A. Schembri a,b School of Chemistry and Molecular Biosciences, the University of Queensland, Queensland, Brisbane, Australia a ; Australian Infectious Diseases Research Centre, the University of Queensland, Queensland, Brisbane, Australia b ; School of Medical Sciences and Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia c ABSTRACT Escherichia coli is a versatile pathogen capable of causing intestinal and extraintestinal infections that result in a huge burden of global human disease. The diversity of E. coli is reflected by its multiple different pathotypes and mosaic genome composition. E. coli strains 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 of E. coli and demonstrated the overlapping relationship between strains from different pathotypes. In combination with proteomic investiga- tion, this analysis revealed core genes that encode surface-exposed or secreted pro- teins that represent potential broad-coverage vaccine antigens. One of these anti- gens, 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 accessory E. coli genes. The work also identified YncE as a novel antigen that could be exploited in the de- velopment of a vaccine against all pathogenic E. coli strains—an important direction given the high global incidence of infections caused by multidrug-resistant strains for which there are few effective antibiotics. IMPORTANCE E. coli is a multifaceted pathogen of major significance to global hu- man health and an important contributor to increasing antibiotic resistance. Given the paucity of therapies still effective against multidrug-resistant pathogenic E. coli strains, novel treatment and prevention strategies are urgently required. In this study, we defined the core and accessory components of the E. coli genome by ex- amining a large collection of draft and completely sequenced strains available from public databases. This data set was mined by employing a reverse-vaccinology ap- proach in combination with proteomics to identify putative broadly protective vac- cine antigens. One such antigen was identified that was highly immunogenic and in- duced 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 pathogenic E. coli. KEYWORDS: Escherichia coli, vaccines, virulence factors E scherichia coli is a bacterium that exists in many different guises. On one hand, it is a common commensal organism of the human small intestine. On the other, it is a rapidly evolving pathogen that is able to acquire and combine different genetic elements into novel and complex gene repertoires. The latter has led to the evolution of E. coli as a multifaceted pathogen, highlighted by aggressive disease outbreaks (1) and the emergence of multidrug-resistant (MDR) lineages (2, 3). Received 26 October 2016 Accepted 27 October 2016 Published 23 November 2016 Citation Moriel DG, Tan L, Goh KGK, Phan M-D, Ipe DS, Lo AW, Peters KM, Ulett GC, Beatson SA, Schembri MA. 2016. A novel protective vaccine antigen from the core Escherichia coli genome. mSphere 1(6): e00326-16. doi:10.1128/mSphere.00326-16. Editor Melanie Blokesch, Swiss Federal Institute of Technology Lausanne Copyright © 2016 Moriel et al. This is an open- access article distributed under the terms of the Creative Commons Attribution 4.0 International license. Address correspondence to Mark A. Schembri, m.schembri@uq.edu.au. *Present address: Danilo G. Moriel, GSK Vaccines Institute for Global Health S.r.l., Siena, Italy. RESEARCH ARTICLE Therapeutics and Prevention crossmark Volume 1 Issue 6 e00326-16 msphere.asm.org 1 on November 2, 2017 by guest http://msphere.asm.org/ Downloaded from