Drug-Resistant Bacteria Are More Clever Than We Thought

Humans and cockroaches get much of the credit for evolutionary adroitness, but it's perhaps bacteria that deserve a turn in the spotlight of the fittest. Anew paper published in the journal Biomicrofluidics suggests that we may have underestimated bacteria and their propensity for overdriven evolution.

We've known well enough that our prokaryotic friends are quite good at adaptation, and that talent—coupled with a whole lot of human nearsightedness—is what's brought us here to the current antibiotic resistance crisis, in which pathogenic bacteria are evolving around our antimicrobal defenses faster than we can develop new ones.

While researchers are making some crucial gains in the hunt for new antimicrobals, the new work suggests it may not be enough to keep up with evolution of antibiotic-resistant bacteria.

"We have to aim at extremely fast acting drugs," Robert Austin, a Princeton biophysicist and the lead author of the current paper, told me. "Drugs that act slowly, or do not kill—are bacteriostatic rather than bacteriosuicidal—also are to be avoided. We have to do searches for new drugs outside the 'ivied halls of academia.' That is, what might look good in a test tube may be extremely dangerous in a complex, high-stress gradient environment."

Based on observations of bacterial development in relatively unlaboratory-like simulations of "natural ecological niches," a rarity in this sort of research, the Princeton team behind the current study found that members of the E. coli strain were accelerating their own evolution by "borrowing" or scavenging strands of leftover viral DNA that were then used toward the bacteria's own antibiotic adaptations.

The ability of bacteria to use viral DNA for their own purposes (usually to develop antiviral defenses) isn't exactly a new revelation. Bacteria don't even always need the viral interloper, and are known to even chase after bits of junk DNA in their environments: genetic scrapping.

What the new work found is that different bacteria use this junk genetic material in very different ways to reach the same results (resistance). It's a subtle bit of cleverness that amounts to evolutionary hedging. If one mutation doesn't do the trick, then bacteria have other mutations that might.

So, the bacterial optimization problem because something more nonlinear; that is, a strain of bacteria under some stress—in the experiments described in the new study it was the antibiotic Cipro—will try a bunch of things at once rather than trying one thing and waiting for it to fail. The effect is startlingly quick adaptation.

"Anything that enhances mutation rates is I think to be avoided in new drug development," Austin said.

Crucially, this revelation even more so puts the emphasis back onto how we use antibiotics in the very first place. "[This] teaches us that antibiotics have to be used much more carefully than they have been up to this point," Austin noted in a separate statement.

Getting a leg up in the antibiotic arms race means handicapping our pathogenic opponents and one way to do that is by taking away the very thing they need to learn and adapt: the antibiotics themselves.