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 Streptococcus pneumoniae D39,a pathogen resp...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 Streptococcus pneumoniae 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,S.pneumoniae 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 S.pneumoniae lacks a stress response pathway.Our findings suggested that the MA results are applicable to within-host scenarios and provide insights into pathogen evolution.展开更多
基金financially supported by Laoshan Laboratory(LSKJ202203203)the National Natural Science Founda-tion of China(31961123002,32270435)+4 种基金the Fundamental Research Funds for the Central Universities of China(202041001)the Shan-dong Provincial Natural Science Foundation(ZR2023QC191)the Postdoctoral Fellowship Program of CPSF under Grant Number GZC20232504the Multidisciplinary University Research Initiative Award from the US Army Research Office(W911NF-09-1-0444)National Institutes of Health award(R35-GM122566 to ML)and(R35-GM131767 to MEW).
文摘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 Streptococcus pneumoniae 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,S.pneumoniae 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 S.pneumoniae lacks a stress response pathway.Our findings suggested that the MA results are applicable to within-host scenarios and provide insights into pathogen evolution.
