Abstract
Enterotoxigenic Escherichia coli (ETEC) is an endemic health threat in underdeveloped nations. Despite the significant effort extended to vaccine trials using ETEC colonization factors, these approaches have generally not been especially effective in mediating cross-protective immunity. We used quantitative proteomics to identify 24 proteins that differed in abundance in membrane protein preparations derived from wild-type vs. a type II secretion system mutant of ETEC. We expressed and purified a subset of these proteins and identified nine antigens that generated significant immune responses in mice. Sera from mice immunized with either the MltA-interacting protein MipA, the periplasmic chaperone seventeen kilodalton protein, Skp, or a long-chain fatty acid outer membrane transporter, ETEC_2479, reduced the adherence of multiple ETEC strains differing in colonization factor expression to human intestinal epithelial cells. In intranasal challenge assays of mice, immunization with ETEC_2479 protected 88% of mice from an otherwise lethal challenge with ETEC H10407. Immunization with either Skp or MipA provided an intermediate degree of protection, 68 and 64%, respectively. Protection was significantly correlated with the induction of a secretory immunoglobulin A response. This study has identified several proteins that are conserved among heterologous ETEC strains and may thus potentially improve cross-protective efficacy if incorporated into future vaccine designs.
Highlights
Enterotoxigenic Escherichia coli (ETEC) is a significant cause of human morbidity due to infectious diarrhea and resultant malnutrition [1]
One of the major causative agents of diarrheal disease is a group of bacteria collectively known as enterotoxigenic Escherichia coli (ETEC)
These organisms can cause disease symptoms ranging from mild diarrhea to a more severe, cholera-like form
Summary
Enterotoxigenic Escherichia coli (ETEC) is a significant cause of human morbidity due to infectious diarrhea and resultant malnutrition [1]. ETEC are a diverse group of pathogens that colonize the small intestine, where they attach to mucosal surfaces using surface antigens known as colonization factors [CFs; [3]. ETEC infections are associated with an acute watery diarrhea that can lead to rapid dehydration [1]. ETEC strains express heat-labile (LT) and/ or heat-stable (ST) enterotoxins [5]. The enzymatic activities of these enterotoxins cause diarrhea by inducing water and electrolyte loss from the intestine of infected subjects [5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
