Glucose Metabolism by Escherichia coli Inhibits Vibrio cholera Intestinal Colonization of Zebrafish

Cholera is a severe acute watery diarrhea that is caused by Vibrio cholerae and is a major problem in developing countries. More than 200 serogroups of Vibrio cholerae have been identified as causative agents of human diarrhea. Of these, serogroups O1 and O139 are the main causes of epidemic cholera. Despite large gains in collective understanding and decades of research, cholera remains a large burden on human health resources worldwide. WHO estimates that over 3 million people contract cholera annually, leading to over 100,000 deaths.

Administration of oral rehydration solution is still the preferred treatment course for cholera. Vaccines may help during an outbreak to limit the spread of cholera, but it cannot save patients who have already contracted the disease. The use of antibiotics to treat cholera is also not recommended because rampant use of antibiotics leads to multidrug resistance.

Every reported pandemic cholera outbreak has been caused by strains of the O1 serogroup of V. cholerae that can be classified into two major biotypes, classical and El Tor. In recent years, the O1 serogroup El Tor biotype has been the major disease-causing biotype, replacing the previously predominant classical biotype. The Ogawa serotype of the El Tor biotype was most common in past years, but recently the Inaba serotype was also reported to cause outbreaks in India. It has been suggested that the ability to metabolize sugars without production of growth inhibitory acidic products might account for the increased evolutionary fitness of the V. cholera EL Tor biotype leading to the displacement of the classical biotype as the predominant cause of epidemic cholera.

To this note, researchers at Wayne State University School of Medicine: Dr. Dhrubajyoti Nag, Dr. Paul Breen, Dr. Jeffery Withey in collaboration with Professor Saumya Raychaudhuri at CSIR- Institute of Microbial Technology in India developed a new glucose feeding model in zebrafish and studied the effect of acid-producing E. coli strains on V. cholerae colonization in the presence of glucose in the zebrafish intestine. Their research work is published in the American Society for Microbiology journal; Infection and Immunity.

The research team observed that when zebrafish were infected with V. cholerae classical strain O395 after glucose feeding, there was a 30-fold decrease in colonization compared to O395 colonization of zebrafish without glucose feeding. In contrast, zebrafish infected with V. cholerae El Tor strain N16961 after glucose feeding, had only 5-fold increase in colonization compared to N16961 colonization of zebrafish without glucose feeding.

Furthermore, when Wayne State University scientists tested if the colonizing E. coli would alter V. cholera colonization in the presence of glucose, they noticed that in the case of the classical strain (O395), there was significantly reduced colonization with 1% glucose and no E. coli. Coinfection with either E. coli strain had no significant effect on V. cholerae O395 colonization in the presence of glucose. In contrast, glucose alone had no significant effect on V. cholerae colonization for the El Tor strain (N16961), however, coinfection with either of the E. coli strains in the presence of glucose caused up to a 40-fold decrease in V. cholerae colonization compared to the coinfected group without glucose feeding and the glucose feeding group without E. coli coinfection.

The study suggests that probiotic E.coli strains plus glucose could be a successful therapeutic measure against V. cholera infection, and the administration of probiotic E. coli could also be used as a preventive measure to reduce the spread of disease during a cholera outbreak.