Extraintestinal Pathogenic Escherichia coli, a Common Human Pathogen: Challenges for Vaccine Development and Progress in the Field

Abstract

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.

Keywords: Escherichia coli; O antigen; antimicrobial resistance; disease burden; extraintestinal pathogenic Escherichia coli; urinary tract infection; vaccine.

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.

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.

Figure 3.

Escherichia coli O serotypes causing extraintestinal infections. Data are from the article by Orskov et al [41]. Abbreviation: UTIs, urinary tract infections.

Figure 4.

Process of in vivo bioconjugation, using recombinant Escherichia coli. Campylobacter oligosaccharyltransferase (PglB) transfers selected O polysaccharides (devoid of lipids) to the Pseudomonas aeruginosa exoprotein A (EPA) protein carrier present in the periplasm. Abbreviation: SEC, secretory pathway.

Figure 5.

Challenges to extraintestinal pathogenic Escherichia coli vaccine development. Individual challenges to vaccine development need to be surmounted to achieve successful technical development, appropriate strain selection, and demonstration of efficacy in the target population. Abbreviation: UTI, urinary tract infection.