Random changes in behavior speed bacteria evolution

Computer modeling of how microbes mutate could provide clues to battling antibiotic resistance

Pseudomonas aeruginosa

PLAYING DEFENSE  Random shifts in behavior could help disease-causing microbes like the bacterium Pseudomonas aeruginosa, pictured above, evolve antibiotic-resistance, a new study suggests. 

James Archer/CDC

Random changes in microbes’ behavior can speed up evolution, a new study shows.

These shifts — called phenotype switches — can promote genetic mutations that help microbes better survive their environment, researchers report online January 19 at BioRxiv.org. Understanding how the microbes evolve is “particularly important for antibiotic resistance,” says study coauthor Bartlomiej Waclaw, a physicist at the University of Edinburgh.

Waclaw and colleagues used computer modeling to look at how an organism’s phenotype — in this case, its growth behavior — might influence its genetic makeup, or genotype, in an unchanging environment. The experiment could represent how bacteria replicate and evolve to reach an antibiotic-resistant state, the researchers suggest.

In the computer model, one growth behavior forced cells into a so-called “fitness valley,” a place where microbes don’t survive well. The other behavior allowed cells to get around the valley unscathed. The cells that survived the entire journey picked up mutations along the way. By randomly switching between the two behaviors, a cell could avoid the valley of death and bounce back even stronger, having quickly acquired evolutionary mutations best for surviving in the environment.

In a real-world scenario, randomly making phenotype switches could help bacteria hold out against antibiotics long enough to develop antibiotic-resistant mutations, the team concludes. Bacteria with optimal behavioral responses to environmental changes, such as the introduction of antibiotics, potentially could evolve antibiotic-resistant mutations relatively quickly — over a time period spanning 10 to 100 generations, not millions of generations, Waclaw says.

The finding points to potential new ways to fight antibiotic resistance. Preventing bacteria from readily adapting to a new environment by forcibly changing their behavior could, in combination with antibiotics, be a way to treat bacterial illnesses, Waclaw says. Forcing bacteria through the fitness valley, for instance, would be “a very slow and painful road for them to take,” he says.

Other researchers wonder how the experiment would hold up in natural settings. “It might not be as simple in nature,” says Glen D’Souza, an evolutionary microbiologist at the Max Planck Institute for Chemical Ecology in Jena, Germany.

Environmental conditions are always changing in nature, not fixed, he says. Although the result is a nice prediction to work with, more experimental validation is needed.

The researchers agree, and think it’s important to uncover different ways that bacteria evolve antibiotic resistance. Microbes resistant to medications already jeopardize treatment and prevention of certain infections, says study coauthor Andrew Tadrowski, also a physicist at the University of Edinburgh. “Identifying the key mechanisms used by microbes during the evolutionary process could be used to stop, or slow down, unwanted microbial evolutions,” he says.

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