Bacteria that have no friends don’t get sad; they get weird. When E. coli cells sense fewer other bacteria around them, their DNA starts to mutate at a faster rate. That’s bad news for humans and our antibiotics. But if we can make bacteria feel less alone, we might be able to slow down their destructive rampages.
“Personally, I find it pretty surprising that this hasn’t been pinned down before,” says Christopher Knight, a lecturer in the University of Manchester’s Faculty of Life Sciences. The discovery didn’t take any kind of high-tech tests. Lead author Rok Krasovec, a member of Knight’s research group, simply grew E. coli bacteria in varying amounts of food. Cells with more food went through a greater number of generations every day, creating denser populations; those with less food multiplied more slowly.
Then Krasovec treated the cells with rifampicin, an antibiotic that’s used for TB. After the treatment, he counted up the survivors–bacteria that had developed resistance to that antibiotic through a random, lucky mutation. He used the frequency of this one mutation to estimate how quickly the bacterial genome was changing overall. Cells growing at the lowest densities, he found, had about 3 times more mutations than those at the highest densities.
Knight notes that when scientists study mutation rates, they often look at strains of bacteria that are specially engineered to mutate at hundreds of times the normal pace. This might help explain why the smaller-scale effect that he and Krasovec found hasn’t been observed before. Still, he says, “a 3-fold change in the chances of an organism getting a mutation that allows its offspring to survive could be pretty biologically significant.”
The scientists used a complex series of tests to tease apart different factors that might be causing more mutations in lonelier bacteria. One by one, they ruled out possibilities: It wasn’t the amount of food the bacteria were given. It wasn’t competition between bacteria squeezed into a small space. It wasn’t stress (though stress can cause a higher mutation rate).
After they’d tested every variable in the bacteria’s environment that they could think of, Knight says, “nothing seemed to matter beyond density.” The mere fact of bacteria being close together slows down their mutation rate.
Further tests showed that the effect depends on a gene called luxS. Bacteria lacking this gene grew just as slowly or quickly as normal bacteria, but their mutation rate stayed the same no matter how dense their populations were.
Scientists already knew that the luxS gene is involved in “quorum sensing.” This is a somewhat creepy trick that lets bacteria tell how many other bacteria are around—and then coordinate their behavior. When they sense that their population has passed a certain threshold, disease-causing bacteria may suddenly turn on genes that make them more harmful to their host. Or they may start growing together in a sticky sheet called a biofilm, rather than drifting around individually.
Knight and Krasovec found that luxS lets E. coli cells respond to population density in a different way: by slowing or quickening their mutation rate. The scientists don’t know yet whether this helps the bacteria adapt and survive.
“It does seem to make intuitive sense,” Knight says. “If an organism finds itself lonely, the trade-off between the undoubted risks and possible benefits of mutation [are] different from when it finds itself in an environment where its relatives are thriving.” In other words, DNA mutations are risky and often harmful. But if a bacterial cell notices that not many of its peers are surviving, it might be a good idea to mix things up genetically. Knight and Krasovec are now trying to figure out whether this is true.
If a flexible mutation rate does help bacteria, then reversing it could help humans. By tapping into this mechanism, we could slow down the rate at which bacteria change their DNA—and maybe even keep them from evolving resistance to our antibiotics so quickly. Whether or not bacteria prefer company, we’d like for some of them to stay lonely.
Image: by Nathan Reading (via Flickr)
Krašovec R, Belavkin RV, Aston JA, Channon A, Aston E, Rash BM, Kadirvel M, Forbes S, & Knight CG (2014). Mutation rate plasticity in rifampicin resistance depends on Escherichia coli cell-cell interactions. Nature communications, 5 PMID: 24776982