Efficient Germ: Human body boosts power of cholera microbe

The stomach produces acid potent enough to kill most microbes, a survival trait that people and other animals have preserved over time. However, some bacteria–including the one that causes cholera–regularly pass through this gauntlet to wreak havoc in the intestines. The result is severe diarrhea that can lead to fatal dehydration.

Scientists in the United States and Bangladesh report in the June 6 Nature that the cholera bacterium Vibrio cholerae, once it’s exposed to the human digestive tract, transforms itself into a pathogen hundreds of times more infectious than the V. cholerae living in rivers and ponds.

In developing countries, poor sanitation systems often permit excreted bacteria to spread into drinking water. When medical scientists test cholera in a laboratory, the microbes they use are typically grown from samples collected in such waters. However, puzzling tests in the 1970s showed that it’s difficult for such laboratory-grown cholera to infect human volunteers but didn’t establish why.

Recently, Andrew Camilli, a microbiologist at Tufts University School of Medicine in Boston, and his colleagues began investigating whether bacteria causing epidemic cholera differ from those typically found in the wild and their test-tube derivatives. The scientists set out to compare V. cholerae isolated directly from stools of cholera patients in Bangladesh with lab descendants of V. cholerae collected from waterways.

The researchers fed mice both kinds of bacteria and, the next day, checked the animals’ small intestines. On average, the V. cholerae from people produced 10 to 100 times as many microbes in each mouse’s gut as the lab-grown bacteria did. The difference was as much as 700-fold.

However, the highly infectious state appears transient, Camilli says. After growing in a lab broth for 18 hours, the bacteria lost their extra virulence.

Suspecting that certain genes turn on or off in bacteria exposed to a person’s digestive tract, Camilli and his colleagues examined the two isolates’ DNA.

Indeed, they found that each of the microbe samples has a distinctive pattern of gene activity. The genes activated in the highly infectious microbe include some known to play roles in iron acquisition and protein manufacture, functions required for bacterial growth.

Other genes highlighted by the comparison encode proteins that might cause the bacterium to loosen its grip on the intestinal wall and leave the body in a person’s stool, says Camilli.

One gene especially active in the highly infectious microbe had not turned up in previous work, including the sequencing of the V. cholerae genome, and Camilli’s team is working to determine what protein that gene encodes.

“The idea that Vibrio cholerae may go through dynamic change in its passage through the human host is exciting,” says Richard A. Finkelstein, a microbiologist at the University of Missouri School of Medicine in Columbia.

However, he says, researchers still need to test whether the two forms of V. cholerae infect the animals differently when given separately.

Knowing which proteins prevail in the most virulent forms of the disease might help scientists create more effective vaccines, Camilli says.