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Genetic swap weakens cholera bug's ability to grow (11-16-00)

Researchers from The University of Texas Health Science Center at San Antonio (UTHSC) have found an ingenious way of lowering the virulence of the bug that causes cholera, a potentially deadly intestinal disease found predominantly in developing countries.

Daniele Provenzano and Karl E. Klose, Ph.D., both from UTHSC’s Department of Microbiology, successfully altered genetic characteristics of the cholera bug—with the result that the new bug appears to grow less rapidly in the intestine, where it normally causes disease. The implications of such a finding are huge, since cholera is responsible for infecting millions of people worldwide, from Southeast Asia to India to Africa to South America.

The study was reported in the Aug. 29 Proceedings of the National Academy of Sciences of the United States of America (PNAS). Provenzano is a Ph.D. candidate studying in Dr. Klose’s laboratory.

“We forced a swap of characteristics in Vibrio cholerae, the bacterium that causes cholera,” Dr. Klose said. “Certain virulence factors regulate the bacterium’s ability to grow inside the small intestine. By altering factors called ‘porins’ that are located on the surface of the bug and through which the bacterium obtains nutrients, we found the bug was less resistant to bile, an acidic liver secretion found in the intestines, and that it could not readily colonize the intestine.”

Cholera rarely occurs in the United States, but the water-borne diarrheal disease is epidemic in most Latin American countries. According to the U.S. Centers for Disease Control and Prevention (CDC), more than a million cases of cholera and 10,000 deaths were recorded in Latin America during the early 1990s.

Cholera is marked by acute diarrhea that can progress to life-threatening dehydration and shock. If left untreated, the disease is fatal in half of cases and death can occur within hours. Vomiting and leg cramps are other symptoms. Modern sewage and water treatment systems have virtually eliminated incidence of the disease in this country.

“We have sampled Gulf of Mexico and Rio Grande water in the lab and have found the presence of Vibrio cholerae,” Provenzano said. “Although our clean water supply prevents cholera from being transmitted from person to person, the potential is here for sporadic cases.” Diners who eat cooked crab or raw oysters run a slight risk of infection, he said.

The current worldwide “seventh pandemic” of cholera began in Indonesia in 1961 and rapidly spread to other parts of Southeast Asia. It reached Bangladesh by 1963, India by 1964, and Iran, Iraq and the Soviet Union by 1966. The disease began affecting West Africa in 1970 and has become epidemic in most of the continent. The Latin America outbreak started in 1991 in Peru and has reached as far north as Mexico, with sporadic cases in the U.S.-Mexico border region.

Interestingly, a “mini-epidemic” of cholera occurred aboard a Texas Gulf Coast oil rig in the 1980s when the crew’s water supply became contaminated, the researchers said.

Provenzano is lead author on the PNAS paper. After completing his doctorate at the Health Science Center, he will begin a post-doctoral fellowship with Dr. John J. Mekalanos at Harvard Medical School.

Dr. Klose, assistant professor of microbiology at UTHSC, is an emerging scholar in the cholera research community. He received his Ph.D. in microbiology from The University of California at Berkeley.

A National Institutes of Health training grant for Provenzano and institutional funding awarded to the Health Science Center by the Howard Hughes Medical Institute supported the study.

Contact: Will Sansom