Vaccines Against Extraintestinal Pathogenic Escherichia coli (ExPEC): Progress and Challenges

Authors

Ling Qiu
Dylan Chirman
Justin R Clark
Yikun Xing
Haroldo Hernandez Santos
Ellen E Vaughan
Anthony W Maresso

Publication Date

1-1-2024

Journal

Gut Microbes

DOI

10.1080/19490976.2024.2359691

PMID

38825856

PMCID

PMC11152113

PubMedCentral® Posted Date

6-2-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, Escherichia coli Infections, Escherichia coli Vaccines, Extraintestinal Pathogenic Escherichia coli, Animals, Vaccine, Escherichia coli, ExPEC, urinary tract infection, UPEC, antigen discovery, vaccine immunology, aging

Abstract

The emergence of antimicrobial resistance (AMR) is a principal global health crisis projected to cause 10 million deaths annually worldwide by 2050. While the Gram-negative bacteria Escherichia coli is commonly found as a commensal microbe in the human gut, some strains are dangerously pathogenic, contributing to the highest AMR-associated mortality. Strains of E. coli that can translocate from the gastrointestinal tract to distal sites, called extraintestinal E. coli (ExPEC), are particularly problematic and predominantly afflict women, the elderly, and immunocompromised populations. Despite nearly 40 years of clinical trials, there is still no vaccine against ExPEC. One reason for this is the remarkable diversity in the ExPEC pangenome across pathotypes, clades, and strains, with hundreds of genes associated with pathogenesis including toxins, adhesins, and nutrient acquisition systems. Further, ExPEC is intimately associated with human mucosal surfaces and has evolved creative strategies to avoid the immune system. This review summarizes previous and ongoing preclinical and clinical ExPEC vaccine research efforts to help identify key gaps in knowledge and remaining challenges.

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