Spontaneous mutations and mutational responses to penicillin treatment in the bacterial pathogen D39.

Unlabelled: Bacteria with functional DNA repair systems are expected to have low mutation rates due to strong natural selection for genomic stability. However, our study of the wild-type D39, a pathogen responsible for many common diseases, revealed a high spontaneous mutation rate of 0.02 per genome per cell division in mutation-accumulation (MA) lines. This rate is orders of magnitude higher than that of other non-mutator bacteria and is characterized by a high mutation bias in the A/T direction. The high mutation rate may have resulted from a reduction in the overall efficiency of selection, conferred by the tiny effective population size in nature. In line with this, D39 also exhibited the lowest DNA mismatch-repair (MMR) efficiency among bacteria. Treatment with the antibiotic penicillin did not elevate the mutation rate, as penicillin did not induce DNA damage and lacks a stress response pathway. Our findings suggested that the MA results are applicable to within-host scenarios and provide insights into pathogen evolution.

Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-024-00220-6.