These days, when the words "resistance" and "bacteria" are used in the news, it is usually some dreary report about some new antibiotic-resistant strain that is threatening the world. But germs aren't the only ones evolving in the eternal battle between human and bacteria. A cool story in Science Translational Medicine reveals that some people in Bangladesh have grown resistant to cholera, which has plagued parts of the country for millenia.

To find this group of "protected ones," Harvard researchers flew to the capital of Bangladesh, Dhaka, and teamed up with local physicians. More recently renown as the site of the Banglasdeshi factory collapse, Dhaka rests on the eastern banks of the Ganges river, where the earliest reports of bacteria Vibrio cholerae were made in Sanskrit.

The most common route of transmission for cholera is through drinking water, but it is only a danger in places with poor sanitation and water filtration systems. Much of Bangladesh, and especially the urban slums of Dhaka, qualifies for this distinction. It is estimated that about half the children in Bangladesh are exposed to the disease by the age of 15. During some outbreaks, mortality rates have exceeded 50 percent, as people succumbed to dehydration, intestinal inflammation, and diarrhea that typify the disease.

Given it's high prevalence and severe lethality, it's not too surprising that this research team discovered evidence of natural selection that has led to members of the society developing cholera resistance. To search for immunity, the scientists recruited 42 Bengali families — 126 individuals in all — from Dhaka and sequenced the genes.

"We sought to understand cholera by studying the genetics of a population that has been affected by the disease for centuries — people in the Ganges River Delta of Bangladesh," said co-senior author Dr. Regina LaRocque, of the Masschusetts General Hospital division of Infectious Diseases. "Our findings are just a first step, but they demonstrate how combining ancient history with the current impact of an infectious disease can be a powerful way of identifying human genes that are important to disease outcome."

Genetic analysis revealed a set of 305 DNA signatures that were more common in this Bengali population than in other groups, like East Asians, Europeans, and Yoruba Africans. Several of these gene variants had a direct relationship with the regulation of hydration and inflammation. Many of the isolated traits encoded protein channels that help cells maintain how much water they carry. Another group of genes involved with the "innate immune response," which is the first line of defense against bacteria like cholera.

In a second analysis, they cross-checked 28 of the uncovered traits in patients who had cholera. Finally, they nailed down that five of these genetic regions, two of which play critical roles with innate immunity, were involved in cholera resistance.

"Understanding the basic biology of a disease is fundamental to making clinically relevant advances in treatment," said LaRocque, who is also an assistant professor of Medicine at Harvard Medical School. "Our laboratory is now working on further studies of the innate immune response to cholera, and we believe this work will be highly relevant to developing improved vaccines."

One place where a cholera vaccine is desperately needed is Haiti. The nation's 2010 earthquake was quickly followed by a massive cholera outbreak, as sanitation deteriorated and drinking water supplies became contaminated. Since then, hundreds of thousands have been infected, and every summer brings a fresh rainy season, harkening a new wave of disease.

Another cool revelation from this project had nothing to do with disease, but rather the ancient heritage of Bangladesh. The authors found that Bengali people from Dhaka descended from an admixture of Gujarati Indians and East Asians, namely Singaporean Chinese. Genetic drift analysis suggests this cultural mixing occurred around 500 AD, which corresponds with the collapse of the Indian Gupta Empire and the rise of the Chinese Tang dynasty.

Source: Karlsson EK, Harris JB, Tabrizi S. Natural Selection in a Bangladeshi Population from the Cholera-Endemic Ganges River Delta. Science Translational Medicine. 2013.