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E. coli: can subtractive reverse vaccinology help design a vaccine?

Escherichia coli is no stranger to the human body. In around 20% of us, E. coli is the predominant species in our gastrointestinal tract, where it lives as a commensal. But when E. coli gets out of hand it can cause anything from gastroenteritis to sepsis to urinary tract infections. It's those problematic aspects that Nesta et al. target in their study in mBio this week. Using a subtractive reverse vaccinology approach, the co-authors uncovered an E. coli protein specific to pathogenesis and designed a vaccine to target it. They argue that a broadly cross-protective E. coli vaccine would yield significant public health benefits.
Subtractive reverse vaccinology is a bioinformatics method in which scientists compare the genome sequences of pathogens and related non-pathogens to identify genes specific to disease for the purpose of developing a vaccine. Nesta et al. identified an E. coli gene they called FdeC this way and showed that it is involved in adhesion and the formation of macrocolonies in disease outside the gastrointestinal tract. They had some measure of success with a FdeC-based vaccine - in a mouse model it proved protective for some infection sites but not others. According to the authors, this evidence of protection argues that functionally characterizing potential vaccine candidates and determining the role of these candidates in pathogenesis could support the development of more effective vaccines - for E. coli and other causes of infection.

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