When faced with an oncoming dose of antibiotics, bacteria work together in a neighborly way. Microbes that are resistant to the drug protect their weaker kin in the colony, HHMI researchers have found. The discovery upends traditional notions of antibiotic resistance and offers a target for new drugs against bacterial infections.
James J. Collins, an HHMI investigator at Boston University, set out to study how bacteria acquire resistance over time. His lab group designed a bioreactor to precisely control the growth of a bacterial colony and allow sample taking or the addition of antibiotics at various times. When they collected data from the bioreactor, they found something unexpected.
“The usual thinking about resistance is that a mutation arises in one bacterium, and then that bacterium has a survival advantage and thrives, growing and dividing, while the others die off,” Collins says. But the team found that the bacterial population as a whole showed far more antibiotic resistance than did small samples of bacteria. And only a few bacteria had resistance-causing genetic mutations.
The scientists found that the few truly antibiotic-resistant bacteria emit a compound called indole that signals the rest of the bacteria to ramp up their defenses. When the nonresistant pathogens sense indole, they turn on a pump that expels antibiotic from the cell, and they turn on chemical pathways that protect them from the toxic molecules antibiotics normally induce inside bacteria.
“Bacteria, although they are unicellular organisms, can behave as a multicellular organism from a population standpoint,” says Collins.
The findings, published September 2, 2010, in Nature, suggest that researchers might combat antibiotic resistance by blocking indole, Collins says. He also says the discovery could change the way resistance is measured in a clinical setting—a single sample from a patient might underestimate the real resistance of a bacterial strain inside the body.
Collins and his colleagues are now returning to some of their original questions, with the new viewpoint in mind. How do antibiotic-resistant supermutants arise? Do weaker bacteria protected by indole eventually develop their own resistance mutations, or eventually die off? The scientists are headed back to the bioreactor for the answers.