Scientists have discovered antibiotic resistance genes in the bacterial flora of a remote South American tribe, which curiously had never before been exposed to antibiotic drugs, possibly shedding light on a phenomenon that has developed countries utterly surrounded.

The Yanomami Amerindians, who live in a remote mountainous area in southern Venezuela, have been isolated from other societies for more than 11,000 years. Nonetheless, it turns out that these people boast genes wired to resist antibiotics in bacteria on the skin, and in the mouths and intestines.

The findings, described in the journal Science Advances, suggest that bacteria in the human body have had the ability to resist antibiotics since long before such drugs were ever used to treat disease.

"These people had no exposure to modern antibiotics; their only potential intake of antibiotics could be through the accidental ingestion of soil bacteria that make naturally occurring versions of these drugs," graduate student Erica Pehrsson, who was involved in the research, said in a statement. "Yet we were able to identify several genes in bacteria from their fecal and oral samples that deactivate natural, semi-synthetic and synthetic drugs."

Thousands of years before people began using antibiotics to fight infections, soil bacteria began producing natural antibiotics to kill competitors. Similarly, microbes evolved defenses to protect themselves from the antibiotics their bacterial competitors would make, likely by acquiring resistance genes from the producers themselves through a process known as horizontal gene transfer.

In recent years, this process has accelerated because antibiotics are prescribed more and more, even in cases when they might not be needed. This allows more bacteria to resist and survive exposure to antibiotics. Consequently, strains of human disease that are much harder to treat have emerged.

Already, primary treatments for a number of life-threatening bacterial infections are not effective in at least 50 percent of the world's patients. And according to the World Health Organization (WHO), that percentage is only likely to increase. In fact, we may be soon find ourselves in a "post-antibiotic era - in which common infections and minor injuries can kill," the WHO said in a recent report.

"We have already run out of drugs to treat some types of multidrug-resistant infections, many of which can be lethal, raising the bleak prospect of a post-antibiotic era," said researcher Gautam Dantas, an associate professor of pathology and immunology at Washington University. (Scroll to read on...)

It is unclear whether the diversity of specific bacteria improves or harms health, researchers say. However, they note that the Yanomami Amerindians some of the most diverse collections of bacteria ever seen in humans - about 60 percent more than the microbiomes of people in industrialized countries.

"Our results bolster a growing body of data suggesting a link between, on one hand, decreased bacterial diversity, industrialized diets and modern antibiotics, and on the other, immunological and metabolic diseases - such as obesity, asthma, allergies and diabetes, which have dramatically increased since the 1970s," explained senior author Maria Dominguez-Bello. "We believe there is something occurring in the environment during the past 30 years that has been driving these diseases, and we think the microbiome could be involved."

Most prior studies on the human microbiome have only focused on Western populations. But this time the researchers looked to a society never exposed to antibiotics, hoping to shed light on how modern culture has played a role in antibiotic resistance.

During the new study, the researchers exposed some of the tribe's bacterial flora to 23 different antibiotics, and found that the drugs were able to kill all of the bacteria. However, they suspect that these susceptible bacteria might carry silent antibiotic resistance genes that could be activated upon exposure to antibiotics.

To test the theory, the scientists used a method called functional metagenomics, which proved their suspicions. The bacterial samples contained many antibiotic resistance genes that can fend off many modern antibiotics.

"However, we know that easily cultured bacteria represent less than 1 percent of the human microbiota, and we wanted to know more about potential resistance in the uncultured majority of microbes," Dantas added. (Scroll to read on...)

So they used the same technique to identify functional antibiotic resistance genes from Yanomami fecal and oral samples without any prior culturing, and identified nearly 30 additional resistance genes. Many of these genes deactivated natural antibiotics, but the scientists also found multiple genes that could resist semi-synthetic and synthetic antibiotics.

"These include, for example, third- and fourth-generation cephalosporins, which are drugs we try to reserve to fight some of the worst infections," explained Dantas. "It was alarming to find genes from the tribespeople that would deactivate these modern, synthetic drugs."

But how could the Yanomami bacteria resist antibiotic drugs that they have never been exposed to before? The research team believes cross-resistance may be the answer - that is, when genes that resist natural antibiotics also have the ability to resist related synthetic antibiotics.

"We've seen resistance emerge in the clinic to every new class of antibiotics, and this appears to be because resistance mechanisms are a natural feature of most bacteria and are just waiting to be activated or acquired with exposure to antibiotics," Dantas concluded.

Researchers are fighting to develop new ways of treating non-viral infections as current options are rendered useless. The hope is that these findings shed more light on the antibiotic resistance problem and help us to avoid a possibly dangerous "post-antibiotic era."

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