Antibiotic resistance is one of the biggest global health challenges. Our most powerful antibiotics become less effective as bacteria change and develop new defense strategies against these drugs. So how quickly can bacteria develop resistance to antibiotics?
Although it depends on the type of bacteria and many other factors, “it can basically be instantaneous over a few days of evolution.” Mark Blaskovicha medicinal chemist and co-founder of the Center for Superbug Solutions at the University of Queensland in Australia, told Live Science. “The selection pressure that leads to new mutations that are able to provide resistance can occur in one generation, or at the doubling point.”
Some bacteria, such as Escherichia colican split or double every 20 minutes. Because they reproduce so quickly, they tend to undergo more genetic changes during each duplication compared to more complex organisms, such as humans, whose cells divide approximately every 24 hours. That means a mutation that helps bacteria avoid antibiotics can be passed on to their offspring or others in the population at that time, Blaskovich said.
The possibility of developing antibiotic resistance also depends on the type of bacteria and the antibiotic. Many antibiotics must enter cells to be effective. Because of this, gram-negative bacteria, which have a outer cell membranetend to be more resistant than Gram-positive bacteria thanks to the added layer of protection.
In 2016, researchers at the Technion-Israel Institute of Technology and Harvard Medical School filled a table the size of petri dish with E. coli bacteria and the antibiotic trimethoprim, which normally kills bacteria that cause urinary tract infections. They divided the massive Petri dish into nine sections, with antibiotic concentrations in each section ranging from zero to 1,000 times the lethal dose for E. coli.
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The scientists found that in just 11 days, the entire population had acquired mutations that made it resistant to even the highest concentration of the antibiotic tested in the experiment.
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But that’s at the population level, Blaskovich noted. With a study like this, “you’re missing the nuances of what’s going on inside individual cells within that population,” he said.
What’s more, when antibiotics fail in the clinic, it’s usually due to an increase in bacteria that already have resistance genes, as opposed to bacteria that evolve new antibiotic resistance mutations over the course of treatment, Blaskovich said. So in real patients, it may take even less time for a population of bacteria to become resistant than in the petri dish experiment, he said.
Occasionally, a small number of bacteria can survive antibiotics better than others in the population. These “stronger” bacteria are likely to grow better than the rest of the population.
there are four common ways bacteria can gain resistance to antibiotics by: modifying their cell walls to stop antibiotics from entering cells, pumping antibiotics out of cells, changing the bacterial protein that the antibiotic targets, and producing enzymes that inactivate the antibiotic.
Each of these mechanisms takes a different time to develop, Blaskovich said. For example, antibiotics that bind to a bacterial target controlled by a single gene can potentially induce rapid mutation, especially when the mutation does not interfere with the organism’s internal function. On the other hand, if antibiotic resistance requires changes that inhibit critical functions in the bacteria, resistance can take much longer to emerge.
One way scientists and clinicians are overcoming antibiotic resistance is by using a combination of drugs with different mechanisms of action. In this way, each antibiotic will have less influence on the evolution of a particular resistance mechanism.
“Over the past 20 to 30 years, we’ve been getting a better understanding of the properties that allow antibiotics to penetrate bacteria,” Blaskovich said. “The biggest obstacle, really, to antibiotic development is just the lack of people doing it.”
