When it comes to fighting antibiotics, E. coli bacteria have each other’s backs.
Just a few drug-resistant bacteria can release a protective substance that makes a whole population resilient to drugs, a new study in the Sept. 2 Nature shows. The findings may lead to new ways of combating drug-resistant germs in humans.
“Antibiotic resistance is a global health issue and we want to understand how and why bacteria become resistant to a particular antibiotic,” says biophysicist Hyun Youk of MIT.
It turns out that when E. coli, a common gut microbe that occasionally causes illness, becomes resistant to an antibiotic, it releases a molecule called indole to share with its more vulnerable neighbors. Indole is a molecule known to help E. coli tolerate stress. By sharing the compound, just a few members of the population can make the whole group of bacteria tolerant of an antibiotic.
“These E. coli cells have developed a very cunning strategy,” Youk says. The finding “highlights how difficult it will actually be to fight off antibiotic resistance.”
A team of scientists from Boston University made the discovery by accident. They were studying E. coli to see which genetic mutations made the bacteria resistant to drugs.
By singling out individual bacteria within a large antibiotic-resistant population, the team found that most individuals were less resistant than the group as a whole. But a few rare individuals were more resistant than the population average.
“We were surprised,” says bioengineer James Collins, a coauthor of the study. “We immediately thought that the resistant guys must be producing something to help out the less resistant guys.”
It turns out that the more resistant bacteria were producing indole. After further analysis, the team found that indole was turning on cellular pumps that push drugs out and was protecting against damage produced by chemically reactive free radicals.
When the researchers looked for genetic changes that might explain the indole production, they found numerous mutations that protected the bacteria against the antibiotic. There weren’t any for increased indole production. It seemed that resistant bacteria, untroubled by the antibiotic, were able to keep right on producing their normal levels of indole, sharing it with neighbors. In contrast, bacteria that aren’t drug resistant stop making indole in response to antibiotics.
But the indole production came at a cost to the resistant bacteria. Since they spent energy making the indole, they had fewer resources to use for their own growth and reproduction and grew more slowly than mutants that didn’t produce indole. Somewhat similar to the evolutionary idea of kin selection, the process may ensure survival of the mutants’ relatives.
“This is the first observed example of altruism in antibiotic resistance,” Youk says. The finding adds to the growing notion that groups of bacteria might behave more like a multicellular organism than traditionally thought, he says.
Collins isn’t quite sure why this type of bacterial altruism would exist. If more vulnerable bacteria died, it would be to the advantage of the resistant ones, which would have more room to multiply and take over.
“It may be that the bacterial populations evolved this as a strategy to help survive transient stresses as a population,” he says. His paper explains that preservation of the bacterial colony as a whole would keep other beneficial mutations in the gene pool.
Youk thinks doctors may one day want to revise their strategy for avoiding antibiotic resistance in people, perhaps by varying the number of pills taken every day to make it harder for resistance to develop in bacteria.
