Scientists have found antibiotic resistance genes in the bacterial flora
of a South American tribe that never before had been exposed to
antibiotic drugs. The findings 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 are huts in an isolated village inhabited by Yanomami Amerindians
in a remote, mountainous area in southern Venezuela. Members of the
tribe were isolated from the modern world and had never been exposed to
antibiotic drugs, but the bacteria on their skin and in their mouths and
intestines still had antibiotic resistance genes.
The research stems from the 2009 discovery of a tribe of Yanomami
Amerindians in a remote mountainous area in southern Venezuela. Largely
because the tribe had been isolated from other societies for more than
11,000 years, its members were found to have among the most diverse
collections of bacteria recorded in humans. Within that plethora of
bacteria, though, the researchers have identified genes wired to resist
antibiotics.
The study, published April 17 in Science Advances, reports
that the microbial populations on the skin and in the mouths and
intestines of the Yanomami tribespeople were much more diverse than
those found in people from the United States and Europe. The multicenter
research was conducted by scientists at New York University School of
Medicine, Washington University School of Medicine in St. Louis, the
Venezuelan Institute of Scientific Research and other institutions.
"This was an ideal opportunity to study how the connections between
microbes and humans evolve when free of modern society's influences,"
said Gautam Dantas, PhD, associate professor of pathology and immunology
at Washington University and one of the study's authors. "Such
influences include international travel and exposure to antibiotics."
Intriguingly, in Dantas' lab, graduate student Erica Pehrsson
searched for and found antibiotic resistance genes in bacteria on the
skin and in the mouths and intestines of tribe members long isolated
from such outside influences.
"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," Pehrsson said. "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, the abundance of antibiotics in medicine and
agriculture has accelerated this process, stimulating the development
and spread of genes that help bacteria survive exposure to antibiotics.
Consequently, strains of human disease that are much harder to treat
have emerged.
"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," Dantas said.
Scientists don't really know whether the diversity of specific
bacteria improves or harms health, Dantas said, but added that the
microbiomes of people in industrialized countries are about 40 percent
less diverse than what was found in the tribespeople never exposed to
antibiotics.
"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," said Maria
Dominguez-Bello, PhD, associate professor of medicine at New York
University Langone Medical Center and senior author of the study. "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."
Dominguez-Bello said the research suggests a link between modern
antibiotics, diets in industrialized parts of the world and a greatly
reduced diversity in the human microbiome -- the trillions of bacteria
that live in and on the body and that are increasingly being recognized
as vital to good health.
The vast majority of human microbiome studies have focused on Western
populations, so access to people unexposed to antibiotics and processed
diets may shed light on how the human microbiome has changed in
response to modern culture, and may point to therapies that can address
disease-causing imbalances in the microbiome.
In the current study, when the researchers exposed cultured bacterial
species from the tribe to 23 different antibiotics, the drugs were able
to kill all of the bacteria. However, the scientists suspected that
these susceptible bacteria might carry silent antibiotic resistance
genes that could be activated upon exposure to antibiotics.
They tested for such activation, and the tests confirmed their
suspicions. The bacterial samples contained many antibiotic resistance
genes that can fend off many modern antibiotics. These genes may turn on
in response to antibiotic exposure.
"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
said.
So the researchers applied the same method, called functional
metagenomics, to identify functional antibiotic resistance genes from
Yanomami fecal and oral samples without any prior culturing. From that
experiment they were able to identify 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," said Dantas. "It was alarming to find genes from the
tribespeople that would deactivate these modern, synthetic drugs."
As for how bacteria could resist drugs that such microbes never
before had encountered, the researchers point to the possibility of
cross-resistance, 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 said.
Funded by the C&D Fund, the Emch Fund, the Helmsley Charitable
Trust, SUCCESS, NAKFI Synthetic Biology, a Washington University I-CARES
award, the Diane Belfer Program for Human Microbial Ecology, an NDSEG
graduate fellowship, a Howard Hughes Medical Institute Early Career
Scientist Award, and grants from the National Institute of Diabetes and
Digestive and Kidney Diseases and the National Institute of General
Medical Sciences of the National Institutes of Health (NIH). NIH grants
DK062429, DP2-DK098089, R01-GM099538 and UH2AR057506.
Journal Reference:
- Jose C. Clemente, Erica C. Pehrsson, Martin J. Blaser, Kuldip Sandhu, Zhan Gao, Bin Wang, Magda Magris, Glida Hidalgo, Monica Contreras, Óscar Noya-Alarcón, Orlana Lander, Jeremy McDonald, Mike Cox, Jens Walter, Phaik Lyn Oh, Jean F. Ruiz, Selena Rodriguez, Nan Shen, Se Jin Song, Jessica Metcalf, Rob Knight, Gautam Dantas, M. Gloria Dominguez-Bello. The microbiome of uncontacted Amerindians. Science Advances, 2015 DOI: 10.1126/sciadv.1500183
Courtesy: ScienceDaily
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