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Extraintestinal Pathogenic Escherichia coli , a Common Human Pathogen: Challenges for Vaccine Development and Progress in the Field
Open accessAbstract
Extraintestinal pathogenic Escherichia coli (ExPEC) is the most common gram-negative bacterial pathogen in humans. ExPEC causes the vast majority of urinary tract infections (UTIs), is a leading cause of adult bacteremia, and is the second most common cause of neonatal meningitis. Increasing multidrug resistance among ExPEC strains constitutes a major obstacle to treatment and is implicated in increasing numbers of hospitalizations and deaths and increasing healthcare costs associated with ExPEC infections. An effective vaccine against ExPEC infection is urgently needed. The O antigen, a component of the surface lipopolysaccharide, has been identified as a promising vaccine target. With the availability of a novel bioconjugation technology it is expected that multivalent O antigen conjugate vaccines can be produced at industrial scale. Clinical proof of concept of a 4-valent O antigen conjugate vaccine is ongoing. An ExPEC vaccine effective against strains that are associated with major diseases and resistant to multiple drugs could be routinely delivered to individuals at risk of developing severe E. coli infection, such as elderly people, individuals undergoing abdominal surgery and prostatic biopsy procedures, and persons at risk of recurrent and/or complicated UTI.
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![Figure 1. Distribution of pathogens among isolates from 80 089 hospital admissions in 19 US hospitals between 2007 and 2010 [10]. Abbreviations: A. baumannii, Acinetobacter baumannii; E. coli, Escherichia coli; E. faecalis, Enterococcus faecalis; E. faecium, Enterococcus faecium; K. pneumoniae, Klebsiella pneumoniae; P. aeruginosa, Pseudomonas aeruginosa; S. aureus, Staphylococcus aureus.](/paper-figures/97e374a447a948278b6c0fb689cafa0f/extraintestinal-pathogenic-i-escherichia-coli-i-a-common-human-pathogen-figure-1.jpg)
![Figure 2. A, Incidence of Escherichia coli bacteremia, by age, in Auckland, New Zealand, between 2005 and 2011. The figure is reproduced from the article by Williamson et al [20]. B, rising numbers of E. coli bacteremia isolates reported to the European Antimicrobial Resistance Surveillance System between 2002 and 2008. Data are from the article by De Kraker et al [16]. Abbreviations: E. coli, Escherichia coli; S. aureus, Staphylococcus aureus; S. pneumoniae, Streptococcus pneumoniae.](/paper-figures/fd45f1f0b20e448fb0034265e77c86e3/extraintestinal-pathogenic-i-escherichia-coli-i-a-common-human-pathogen-figure-2.jpg)
![Figure 3. Escherichia coli O serotypes causing extraintestinal infections. Data are from the article by Orskov et al [41]. Abbreviation: UTIs, urinary tract infections.](/paper-figures/2bf2807017af4bbf92cbf8bc0f1753bc/extraintestinal-pathogenic-i-escherichia-coli-i-a-common-human-pathogen-figure-3.jpg)
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“There are no licensed vaccines against E. coli or group B S. agalactiae, despite these two pathogens being the major causes of bacterial meningitis in neonates.”
From Global etiology of bacterial meningitis: A systematic review and meta-analysis. (2018) · cites this paper as [14]
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Cites
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Self-citationThe structures of Escherichia coli O-polysaccharide antigens
Stenutz, R., Weintraub, A., & Widmalm, G. (2006) · FEMS Microbiology Reviews · doi:10.1111/j.1574-6976.2006.00016.x · Cited by 410
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Cited by
Sorted by citations
Terlizzi, M., Gribaudo, G., & Maffei, M. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.01566 · Cited by 627
Progress in Alternative Strategies to Combat Antimicrobial Resistance: Focus on Antibiotics
Murugaiyan, J., Kumar, P. A., Rao, G. S., Iskandar, K., Hawser, S., Hays, J. P., Mohsen, Y., Adukkadukkam, S., Awuah, W. A., Alvarez, M. J. R., et al. (2022) · Antibiotics · doi:10.3390/antibiotics11020200 · Cited by 628
Liu, C. G., Green, S. I., Min, L., Clark, J. R., Salazar, K. C., Terwilliger, A. L., Kaplan, H. B., Trautner, B. W., Ramig, R. F., & Maresso, A. W. (2020) · mBio · doi:10.1128/mbio.01462-20 · Cited by 411
Genomic surveillance for antimicrobial resistance — a One Health perspective
Djordjevic, S. P., Jarocki, V. M., Seemann, T., Cummins, M. L., Watt, A. E., Drigo, B., Wyrsch, E. R., Reid, C. J., Donner, E., & Howden, B. P. (2023) · Nature Reviews Genetics · doi:10.1038/s41576-023-00649-y · Cited by 388
The role of vaccines in preventing bacterial antimicrobial resistance
Jansen, K. U., Knirsch, C. A., & Anderson, A. S. (2018) · Nature Medicine · doi:10.1038/nm.4465 · Cited by 355
Metadata
- Authors
- Poolman, J. T., & Wacker, M.
- Affiliations
- Janssen (Netherlands) (NL)
- Corresponding author
- Poolman, Jan T.
- ORCID
- Poolman, Jan T.
- Venue
- Journal of Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-09-02
- Volume
- 213
- Issue
- 1
- Pages
- 6-13
- ISSN
- 0022-1899 (ISSN-L)
- 1537-6613
- PMC
- PMC4676548
- OpenAlex
- W2243816940
- Cited by
- 246
- References
- 48
- Citations by year
- 2026: 20 · 2025: 25 · 2024: 31 · 2023: 29 · 2022: 30 · 2021: 21 · 2020: 27 · 2019: 26 · 2018: 15 · 2017: 11 · 2016: 11
- FWCI
- 1.36
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- The Journal of Infectious Diseases (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Microbiology › Escherichia coli research studies
- Health Sciences › Medicine › Urology › Urinary Tract Infections Management
- Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
- Keywords
- extraintestinal pathogenic Escherichia coli, vaccine development, lipopolysaccharide, urinary tract infection, bacteremia, neonatal meningitis, multidrug resistance, bioconjugation, multivalent vaccine, vaccine targets
- MeSH terms
- Escherichia coli, Escherichia coli Infections, Humans, Urinary Tract Infections, O Antigens, Escherichia coli Vaccines, Drug Resistance, Bacterial
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