The millions of microbes that crowd the human intestinal tract are teeming with new antibiotic resistance genes that could jump to disease-causing pathogens, according to researchers from Harvard University.

An artist's conception of microbial ecology in the gut. Pathogenic bacteria (green coats) receiving Penicillin resistance genes from beneficial gut bacteria (blue rounded chains) Image courtesy of A. Canossa, M. Sommer and G. Dantas

They found more than 90 undiscovered bacterial genes capable of conferring antibiotic resistance hiding in microbes harvested from two healthy adults. They report their findings in Science today (August 27).

"I thought this was an incredibly cool story," Gerry Wright, McMaster University chemical biologist, told The Scientist. "It tells you just how ignorant we are of microbial ecology."

Wright, director of McMaster's Michael G. DeGroote Institute for Infectious Disease Research, said that the findings raise several key questions. "If there's so much resistance out there, how come [antibiotics] work at all?" asked Wright, who was not involved with the study. "It either means that we really don't understand how antibiotics work or we really don't understand how microbes work."

This lack of understanding is underscored by the fact that humans have exposed their bodies to a potentially dangerous flood of antibiotics -- directly in medicines and indirectly through agriculture and cleaning products -- for decades. This exposure has likely selected for the newly discovered antibiotic resistance genes in our internal microbiome, according to lead author Morten Sommer, a postdoc in Harvard geneticist George Church's lab. "And that could be a problem when the microbiome interacts with disease-causing microbes," he told The Scientist.

Sommer and his colleagues analyzed saliva and fecal samples from two healthy volunteers who had not been treated with antibiotics for at least one year, and the researchers isolated more than 500 bacterial strains. They cloned genes from those strains, inserted them into E. coli hosts, and then exposed the E. coli to 13 different antibiotics to determine which genes conferred resistance.

Stuart Levy, Tufts University microbiologist and geneticist, agreed that the study highlights the dangers of irresponsible antibiotic use. He told The Scientist that pathogenic bacteria could easily add antibiotic resistance genes to their genomes via horizontal gene transfer. "There's every chance that [antibiotic resistance genes] could come out of [the microbiome] genome and become a force for resistance in bacteria that we face," said Levy, who is also president of the Alliance for the Prudent Use of Antibiotics. "The majority of antibiotic resistance genes reside in bacteria that are harmless. These are reservoirs of antibiotic resistance." Indeed, Sommer and his colleagues are now searching for chemical signatures of horizontal gene transfer in known resistance genes.

But just because a cache of antibiotic resistance genes exists in our own guts doesn't mean that bacteria are readily swapping them. "If there was horizontal gene transfer, you would expect that [antibiotics] would be useless by now," said Wright. While some multi-drug resistant strains of pathogenic bacteria have emerged recently, many antibiotics are still effective if administered properly.

In addition to finding scores of new antibiotic resistance genes, Sommer and his colleagues showed that almost half of the already identified resistance genes they isolated from the gut were identical to antibiotic resistance genes now found in clinically pathogenic microbes, such as pathogenic strains of E. coli and Salmonella enterica.

While this does not conclusively prove that horizontal gene transfer has occurred between beneficial bacteria in the human gut and disease-causing bacteria, said Sommer, "It does say that there's a close evolutionary history between strains in the human microbiome and pathogens."


Related stories:

The Microbial Health Factor
[August 2009]

The number two-ome
[July 2009]

Mysterious resistance
[September 2008]