A Novel Protective Vaccine Antigen from the Core <named-content content-type="genus-species">Escherichia coli</named-content> Genome
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 ma...
Enregistré dans:
| Auteurs principaux: | , , , , , , , , , |
|---|---|
| Format: | article |
| Langue: | EN |
| Publié: |
American Society for Microbiology
2016
|
| Sujets: | |
| Accès en ligne: | https://doaj.org/article/8f46350c3e904893b09e7efda4a7cb05 |
| Tags: |
Ajouter un tag
Pas de tags, Soyez le premier à ajouter un tag!
|
| id |
oai:doaj.org-article:8f46350c3e904893b09e7efda4a7cb05 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:8f46350c3e904893b09e7efda4a7cb052021-11-15T15:22:04ZA Novel Protective Vaccine Antigen from the Core <named-content content-type="genus-species">Escherichia coli</named-content> Genome10.1128/mSphere.00326-162379-5042https://doaj.org/article/8f46350c3e904893b09e7efda4a7cb052016-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00326-16https://doaj.org/toc/2379-5042ABSTRACT 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 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 accessory E. coli genes. The work also identified YncE as a novel antigen that could be exploited in the development 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 human 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 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 pathogenic E. coli.Danilo G. MorielLendl TanKelvin G. K. GohMinh-Duy PhanDeepak S. IpeAlvin W. LoKate M. PetersGlen C. UlettScott A. BeatsonMark A. SchembriAmerican Society for MicrobiologyarticleEscherichia colivaccinesvirulence factorsMicrobiologyQR1-502ENmSphere, Vol 1, Iss 6 (2016) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Escherichia coli vaccines virulence factors Microbiology QR1-502 |
| spellingShingle |
Escherichia coli vaccines virulence factors Microbiology QR1-502 Danilo G. Moriel Lendl Tan Kelvin G. K. Goh Minh-Duy Phan Deepak S. Ipe Alvin W. Lo Kate M. Peters Glen C. Ulett Scott A. Beatson Mark A. Schembri A Novel Protective Vaccine Antigen from the Core <named-content content-type="genus-species">Escherichia coli</named-content> Genome |
| description |
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 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 accessory E. coli genes. The work also identified YncE as a novel antigen that could be exploited in the development 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 human 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 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 pathogenic E. coli. |
| format |
article |
| author |
Danilo G. Moriel Lendl Tan Kelvin G. K. Goh Minh-Duy Phan Deepak S. Ipe Alvin W. Lo Kate M. Peters Glen C. Ulett Scott A. Beatson Mark A. Schembri |
| author_facet |
Danilo G. Moriel Lendl Tan Kelvin G. K. Goh Minh-Duy Phan Deepak S. Ipe Alvin W. Lo Kate M. Peters Glen C. Ulett Scott A. Beatson Mark A. Schembri |
| author_sort |
Danilo G. Moriel |
| title |
A Novel Protective Vaccine Antigen from the Core <named-content content-type="genus-species">Escherichia coli</named-content> Genome |
| title_short |
A Novel Protective Vaccine Antigen from the Core <named-content content-type="genus-species">Escherichia coli</named-content> Genome |
| title_full |
A Novel Protective Vaccine Antigen from the Core <named-content content-type="genus-species">Escherichia coli</named-content> Genome |
| title_fullStr |
A Novel Protective Vaccine Antigen from the Core <named-content content-type="genus-species">Escherichia coli</named-content> Genome |
| title_full_unstemmed |
A Novel Protective Vaccine Antigen from the Core <named-content content-type="genus-species">Escherichia coli</named-content> Genome |
| title_sort |
novel protective vaccine antigen from the core <named-content content-type="genus-species">escherichia coli</named-content> genome |
| publisher |
American Society for Microbiology |
| publishDate |
2016 |
| url |
https://doaj.org/article/8f46350c3e904893b09e7efda4a7cb05 |
| work_keys_str_mv |
AT danilogmoriel anovelprotectivevaccineantigenfromthecorenamedcontentcontenttypegenusspeciesescherichiacolinamedcontentgenome AT lendltan anovelprotectivevaccineantigenfromthecorenamedcontentcontenttypegenusspeciesescherichiacolinamedcontentgenome AT kelvingkgoh anovelprotectivevaccineantigenfromthecorenamedcontentcontenttypegenusspeciesescherichiacolinamedcontentgenome AT minhduyphan anovelprotectivevaccineantigenfromthecorenamedcontentcontenttypegenusspeciesescherichiacolinamedcontentgenome AT deepaksipe anovelprotectivevaccineantigenfromthecorenamedcontentcontenttypegenusspeciesescherichiacolinamedcontentgenome AT alvinwlo anovelprotectivevaccineantigenfromthecorenamedcontentcontenttypegenusspeciesescherichiacolinamedcontentgenome AT katempeters anovelprotectivevaccineantigenfromthecorenamedcontentcontenttypegenusspeciesescherichiacolinamedcontentgenome AT glenculett anovelprotectivevaccineantigenfromthecorenamedcontentcontenttypegenusspeciesescherichiacolinamedcontentgenome AT scottabeatson anovelprotectivevaccineantigenfromthecorenamedcontentcontenttypegenusspeciesescherichiacolinamedcontentgenome AT markaschembri anovelprotectivevaccineantigenfromthecorenamedcontentcontenttypegenusspeciesescherichiacolinamedcontentgenome AT danilogmoriel novelprotectivevaccineantigenfromthecorenamedcontentcontenttypegenusspeciesescherichiacolinamedcontentgenome AT lendltan novelprotectivevaccineantigenfromthecorenamedcontentcontenttypegenusspeciesescherichiacolinamedcontentgenome AT kelvingkgoh novelprotectivevaccineantigenfromthecorenamedcontentcontenttypegenusspeciesescherichiacolinamedcontentgenome AT minhduyphan novelprotectivevaccineantigenfromthecorenamedcontentcontenttypegenusspeciesescherichiacolinamedcontentgenome AT deepaksipe novelprotectivevaccineantigenfromthecorenamedcontentcontenttypegenusspeciesescherichiacolinamedcontentgenome AT alvinwlo novelprotectivevaccineantigenfromthecorenamedcontentcontenttypegenusspeciesescherichiacolinamedcontentgenome AT katempeters novelprotectivevaccineantigenfromthecorenamedcontentcontenttypegenusspeciesescherichiacolinamedcontentgenome AT glenculett novelprotectivevaccineantigenfromthecorenamedcontentcontenttypegenusspeciesescherichiacolinamedcontentgenome AT scottabeatson novelprotectivevaccineantigenfromthecorenamedcontentcontenttypegenusspeciesescherichiacolinamedcontentgenome AT markaschembri novelprotectivevaccineantigenfromthecorenamedcontentcontenttypegenusspeciesescherichiacolinamedcontentgenome |
| _version_ |
1718428083899334656 |