Scientific Method / Science & Exploration

Antibiotic overuse may give bacteria an evolutionary boost

Switches bugs into a high mutation state, fueling adaptation.

Multiple drug-resistant Staphylococcus aureus bacteria seen under an electron microscope.
Photo: CDC

By flooding our environment with antibiotics, people may alter a little-appreciated but profound aspect of bacterial evolution: the very pace at which it occurs. Bacteria may evolve more rapidly and more radically than just a few decades ago.

This proposition is still a hypothesis, but it’s an intriguing one. While drug resistance is a well-known consequence of antibiotic use, a global acceleration of bacterial mutability could make drug resistance more common and shape pathogens in unpredictable ways.

"Human activities might be altering the fundamental tempo of bacterial evolution," write geneticists Michael Gillings of Australia’s Macquarie University and Hatch Stokes of the University of Technology in a June Trends in Ecology and Evolution paper.

Gillings and Stokes start by describing what’s widely known: The world is inundated by antibiotics. Drugs consumed by people or contained in consumer products end up in sewage, where they’re unaffected by waste treatment and become part of water cycles. The same goes for drugs consumed by animals, which in the United States accounts for 80 percent of antibiotic use. Antibiotic-rich manure is routinely spread on farms.

'Baseline bacterial evolution is a bell-shaped curve, and we are pushing that curve.'

Subjected to environments that favor drug-tolerating individuals, bacteria have evolved in predictable ways, and antibiotic resistance has reached near-crisis proportions. Historical scourges like tuberculosis and pneumonia have returned with a vengeance. Physicians are running quickly through a shrinking roster of still-effective drugs. Because bacteria easily swap genetic material, genes that neutralize antibiotics aren’t just found in target pathogens, but have diffused throughout the world’s microbial populations.

That much is obvious. But according to Gillings and Stokes, something more subtle could be happening. It stands to mathematical reason that natural selection in antibiotic-flooded environments wouldn’t only favor microbes possessing superbug genes, but microbes with especially high mutation rates that increased their chances of randomly producing a superbug mutation.

"Rates of evolution are themselves selected for higher evolvability," said Gillings. "Baseline bacterial evolution is a bell-shaped curve, and we are pushing that curve to the right."

Mechanisms exist that allow bacteria to become more evolvable. When bugs are exposed to environmental stress, what’s known as an SOS response kicks in, diverting cellular energies to repairing DNA and inducing new mutations.

Bacterial mutations also arise through a mix-and-match recombination of genetic command elements called integrons. A bacterium may contain hundreds of integrons, most of which are inactive at any given time—but in response to stress, dormant integrons become active.

Schematic illustration of increasing mutation rates (x-axis) resulting from antimicrobial selection pressure.
Image: Gillings et al./Trends in Ecology and Evolution

Another source of mutations is lateral gene transfer, in which pieces of genetic material float freely between microbes. Individual genes can be exchanged in this manner, as can entire arsenals of genetic units, such as the NDM-1 resistance factor that emerged in India in 2010 and breaks down entire classes of common antibiotics.

Using these mutation mechanisms comes at a heavy cost to individual microbes, noted Mark Toleman, a Cardiff University microbiologist who studies NDM-1. "The general direction of this change is down hill and detrimental to the genome of the bacteria," he said.

According to Gillings and Stokes, antibiotic ubiquity makes that price worthwhile for many bacteria. "We are flooding the world with selective agents," said Gillings, and this may have changed the standard cost-balance equations that govern whether higher evolvability is worth the costs. It’s better to be alive and damaged than dead.

The researchers say these increased mutation rates will generate new forms of antibiotic resistance and other, as-yet-unpredicted changes. "The processes we describe apply equally to all genes in bacterial genomes, not just those that deal with resistance," Gillings said—and it won’t only be a few disease-causing pathogens that speed up, but many if not most microbes.

Not everyone is convinced. Evolutionary biologist Joanna Masel of the University of Arizona, a specialist in bacterial evolvability, said it’s not yet known whether selection pressures exerted by antibiotics are significantly more intense than other forces shaping bacterial evolution.

"There’s a lot of selection pressure on bacteria all the time. They are fighting off viruses and other parasites. They are evading predators. They are having cutthroat competitions" with other bacteria, Masel said.

"Antibiotics clearly matter. Bacteria have evolved in response to them," Masel continued. "But it’s quite another claim that such evolution is a bigger deal than the many, many other things that make bacteria evolve all the time."

"We could be wrong," Gillings said. "What is needed is for people to think about this problem and to design experiments to test our ideas."

Continued Gillings, "We need key data to be sure, but even if there is only a one percent chance that we are right—and I believe it’s more like 99 percent—it’s a phenomenon that needs to be seriously considered."

Citation: "Are humans increasing bacterial evolvability?" By Michael R. Gillings, H.W. Stokes. Trends in Ecology & Evolution, Vol. 27 Issue 6, June 2012.

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