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Bioengineered 'Bacterial Communication' Blocks Cholera Spread

Bacteria don’t simply reproduce and “infect”, they also actively communicate via specialized signaling molecules with other bacteria, both of the same species, and quite different species.

Bio-engineers have learned how to exploit this communicative activity–using commensal, or co-existing, bacteria– to attack pathogenic (disease causing), bacterial strains. The targeted bacteria: Vibrio cholerae, the germ that causes cholera, one of the scourges of the developing world.

Cholera is also often the first disease to appear following intense bombing in urban war zones, due to the rupturing of sewer pipes and the leakage of sewage into the water supply.

Two Cornell bio-engineers, Faping Duan and John C. March, successfully transformed a strain of E. coli into a “commensal communicator” that blocked the virulence of V. cholerae, the bacteria that causes cholera, in mice.

Using a “stably transformed” strain of Escherichia coli (known as Nissle 1917 or Nissle cqsA) that over-expressed a chemical communicator known as CAI-1 (cholera auto-inducer 1). In previous experiments, this molecule was shown to prevent virulence (rapid growth) in the presence of another signaling molecule–auto-inducer 2.

It is believed that these chemical signals induce the targeted bacteria to alter their gene expression “profiles” related to reproduction.

The researchers wanted to test the effect of this molecular communication on V. cholerae virulence gene expression and colonization. For their test subjects, researchers use an infant mouse model.

Quoting from the abstract: “We found that pretreatment of mice for 8 hours with Nissle engineered to express CAI-1 (Nissle-cqsA) greatly increased the mice survival rates (92%) following ingestion of V. cholerae.” The shorter the time period between pretreatment (with the E. coli strain) and ingesting (of the V. cholerae), the lower the survival percentage–but the delayed (4 hour) pre-treatment still offered a 77% increased survival rate to the mice. Treatment at the same time as ingestion increased survival rates by 29%.

The researchers also found an “80% reduction in cholera toxin binding to the intestines of mice pretreated for 8 hours with Nissle-cqsA. Further, the numbers of V. cholerae in treated mouse intestines was reduced by 69% after 40 h.”

This important research on communication between commensal bacteria demonstrates an easily administered, economical and effective prevention treatment that will hopefully be brought into use (pending human trials) to prevent cholera in humans,  and, that the technique can be applied to preventing other human diseases.

By 12 February 2009, the number of cases of infection by cholera in sub-Saharan Africa had reached 128,548 and the number of fatalities, 4,053.

Vibrio cholerae, the bacteria that causes the disease cholera (a disease that usually spreads via a tainted water supply or water table), is actually present in many peoples’ intestines, only in quite small numbers.  Most of the bacteria that are ingested die in the acidic environment of the stomach. However, if the bacteria are able to make it past this natural barrier and into the intestines, and from there through the mucus lining, a colony of the rod-shaped microbes could take hold and quickly bloom, altering the salt content of the intestines, and causing severe diarrhea, eventual dehydration, and, in the case of infants and those with compromised immune systems, sometimes death.

Ethics note:

Using animals  for scientific research has been the subject of many protests and calls for testing bans. However, given the inestimable value of live animal models for disease prevention research, it would seem that the adoption of ethical/humane treatment rules is more warranted, rather than any outright ban. Without animal models, researchers would be forced to guess at outcomes and gamble with human lives (via administering untested vaccines, etc.), risking lawsuits, the shutting down of research efforts, and ultimately, the failure to find cures for a myriad of human diseases.

Results of this bio-engineering research (‘Engineered bacterial communication prevents Vibrio cholerae virulence in an infant mouse model’) were published on the Proceedings of the National Academy of Sciences website, May 13, 2010.

top photo (scanning electron micrograph: V. cholerae) and cholera chart:  Public domain



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