THE PROBLEM
Shiga toxin (Stx)-producing Escherichia coli (STEC) and enteroaggregative E. coli (EAEC) are two different types of bacteria that can contaminate food or water and cause outbreaks and sporadic cases of diarrhea. STEC cause a bloody diarrhea for which there is a sequela of infection, the hemolytic uremic syndrome (HUS), that is sometimes fatal. EAEC are rarely fatal but cause a significant loss of man hours for deployed military personnel (DPM) as well as acute and persistent diarrhea in children in developing countries and in the immunocompromised. Both of these pathogenic types of E. coli have unique ways to colonize and persist in the intestine where they produce toxins. The combination of bacterial colonization and the action of the toxins lead to disease, and we seek to understand the mechanisms by which these two different E. coli cause illness. On rare occasions, hybrid STEC/EAEC strains have caused illness, including one large outbreak with at least 800 cases of HUS.
OUR APPROACH
We evaluate the pathogenesis of STEC and EAEC in mouse models developed in our laboratory. We have found that some STEC are more pathogenic in animals than other STEC, and we are investigating the reasons for those variations in virulence. We are also examining the relative toxicity of Stx subtypes on tissue culture cells and how those subtypes influence each other in mice and on cells. We continue to evaluate the efficacy of antibody treatments for the toxins in the mouse model. We are assessing EAEC isolates from DPM for virulence traits as well as pathogenicity in mice where they cause a failure-to-thrive. We hope to identify virulence factors from those EAEC that have the potential to serve as vaccine candidates.
"In 2017 more than 200 Marine Corp recruits became ill with Shiga toxin-producing E. coli. The Shiga toxin type 2 antibody being tested in our lab may have reduced the severity of illness among these recruits."