Modeling Diarrheagenic E. coli single infections and co-infections: Specific roles of diet, pathogen and microbiome

Project Details

Diarrheal diseases in children is still a major global problem. According to the World Health Organization (WHO), diarrhea is the second leading causes of deaths in children under the age of 5 years. Children are generally more susceptible to enteric infections due to their less developed immune system and in addition, many of these children still have recurrent diarrhea every year contributing to the infection-malnutrition cycle leading to impaired growth and development. The MAL-ED and GEMS are two major case-control studies that have recognized Diarrheagenic E. coli specifically Enteroaggregative E. coli (EAEC), Enteropathogenic E. coli (EPEC) and Enterotoxigenic E. coli (ETEC) as some of the major causes of moderate to severe diarrhea among children in developing countries. Dual Infections with these pathogens have been increasingly recognized in several recent studies of diarrhoea around the world. Recent, studies of diarrheal etiology have begun to describe co-infections, suggesting patients infected with these pathogens may experience more severe disease outcome than single infections.


This research focuses primarily on developing an EPEC murine model and in turn use this model to understand the pathogenesis mechanism and disease severity that might be involved during single infections and co-infections of EPEC with EAEC and also with ETEC. An EPEC diarrheal mouse model has been developed and has shown colonization and inflammatory responses produced during EPEC infection. ETEC enhances EPEC co-infection with increased IL-6 and IL-8 inflammatory responses in vitro and also in vivo with C57Bl/6 mice developing severe diarrhea and acute inflammatory responses. However, EAEC and EPEC co-infections have antagonistic effects with diminished inflammatory responses in vitro.  Future directions are to understand the pathogenesis mechanism that is involved, focusing mainly on virulence genes that might be involved during these co-infections.


Project History

This project has grown from a master’s thesis focused mainly on determining the prevalence of enteric pathogens affecting children in rural communities of the Vhembe District in Limpopo province, South Africa. Children under the age of 5 in these settings were found to be infected with S. flexneri and a high burden of Diarrheagenic E. coli pathotypes. Most of these children had mixed infections of Diarrheagenic E. coli. This led to trying to understand the pathogenesis mechanism and disease severity that might be involved during Diarrheagenic E. coli co-infections specifically focusing on EAEC with EPEC and EPEC with ETEC co-infections.



Limpopo Province, South Africa