Beneficial mutations, scientists say, play a key role in bacterial adaptation, but little is known about the effects these mutations have on bacterial fitness across genetic backgrounds and environments.
Antibiotic resistance, often cited as an example of bacterial adaption, is thought to occur in the presence of antibiotics because resistance mutations confer fitness costs in antibiotic-free environments. But antibiotic resistance is costly for organisms to maintain; for example, mutations that reduce antibiotic uptake also restrict the amount of nutrients entering the cell. Consequently, in the absence of antibiotics, nonresistant bacteria will outcompete resistant bacteria.
But this month, researchers from UC Irvine and Faculté de Médecine Denis Diderot have reported that, by stressing bacteria through growing them at a high temperature, the bacteria could spontaneously develop resistance to the antibiotic rifampicin. And they said, the resistance mutations proved highly beneficial in the absence of antibiotics, depending on both the background of the mutation and the environment.
In their study reported in published in BMC Evolutionary Biology, the researchers documented the selection and fixation of resistant mutations in populations of Escherichia coli B that had never been exposed to antibiotics but instead evolved for 2,000 generations at high temperature.
Specifically, the investigators found parallel mutations within the rpoB gene that encodes the RNA polymerase beta subunit. These amino acid substitutions conferred different levels of rifampicin resistance, with mutations typically appearing early and becoming fixed early in the evolution experiment. The scientists were able to confirm the high advantage of these mutations at 42.2°C in glucose-limited medium, but the rpoB mutations had different fitness effects across three genetic backgrounds and six environments.
This is in contrast, they say, to most previous studies showing that rifampicin resistance is deleterious in the absence of the antibiotic and that compensatory mutations are required for resistance to persist.
The mutations responsible for rifampicin resistance had different effects in other strains of E. coli. In each type of bacteria tested, the mutated subunit of the RNA polymerase rpoB allowed them to grow in the presence of rifampicin, but unlike the original test strain they did not necessarily have a growth advantage at high temperature.
Olivier Tenaillon, Ph.D., of the Faculté de Médecine Xavier Bichat, Paris, who led this study said, “Our study shows that antibiotic resistance can occur even in the absence of antibiotics and that, depending on the type of bacteria, and growth conditions, rather than being costly to maintain can be highly beneficial. Given that rifampicin is used to treat serious bacterial infections such as tuberculosis, leprosy, Legionnaire’s disease, and for prophylaxis in cases of meningococcal meningitis, this development has important implications for public health.”