The Molecular Basis for Control of ETEC Enterotoxin Expression in Response to Environment and Host |
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| Authors: | James R. J. Haycocks Prateek Sharma Anne M. Stringer Joseph T. Wade David C. Grainger |
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| Affiliation: | 1 Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom, ; 2 Wadsworth Center, New York State Department of Health, Albany, New York, United States of America, ; 3 Department of Biomedical Sciences, School of Public Health, University at Albany, SUNY, Albany, New York, United States of America, ; National Institutes of Health, United States of America, |
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| Abstract: | Enterotoxigenic Escherichia coli (ETEC) cause severe diarrhoea in humans and neonatal farm animals. Annually, 380,000 human deaths, and multi-million dollar losses in the farming industry, can be attributed to ETEC infections. Illness results from the action of enterotoxins, which disrupt signalling pathways that manage water and electrolyte homeostasis in the mammalian gut. The resulting fluid loss is treated by oral rehydration. Hence, aqueous solutions of glucose and salt are ingested by the patient. Given the central role of enterotoxins in disease, we have characterised the regulatory trigger that controls toxin production. We show that, at the molecular level, the trigger is comprised of two gene regulatory proteins, CRP and H-NS. Strikingly, this renders toxin expression sensitive to both conditions encountered on host cell attachment and the components of oral rehydration therapy. For example, enterotoxin expression is induced by salt in an H-NS dependent manner. Furthermore, depending on the toxin gene, expression is activated or repressed by glucose. The precise sensitivity of the regulatory trigger to glucose differs because of variations in the regulatory setup for each toxin encoding gene. |
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