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

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.

Correction:Spontaneous mutations and mutational responses to penicillin treatment in the bacterial pathogen Streptococcus pneumoniae D39

Due to technical errors,Ho-Ching T.Tsui and Malcolm E.Winkler,both collaborators who made substantial contributions to this work and were previously acknowledged,did not receive emails regarding authorship consent and were inadvertently omitted from the author list.We have now rectified this oversight and added them to the author list.

Contribution of the SOS response and the DNA repair systems to norfloxacin induced mutations in E.coli

Antibiotic-resistant bacteria severely threaten human health.Besides spontaneous mutations generated by endogenous factors,the resistance might also originate from mutations induced by certain antibiotics,such as the fluoroquinolones.Such antibiotics increase the genome-wide mutation rate by introducing replication errors from the SOS response pathway or decreasing the efficiency of the DNA repair systems.However,the relative contributions of these molecular mechanisms remain unclear,hindering understanding of the generation of resistant pathogens.Here,using newly-accumulated mutations of wild-type and SOS-uninducible Escherichia coli strains,as well as those of the strains deficient for the mismatch repair(MMR)and the oxidative damage repair pathways,we find that the SOS response is the major mutagenesis contributor in mutation elevation,responsible for~30–50%of the total base-pair substitution(BPS)mutation-rate elevation upon treatment with sublethal levels of norfloxacin(0~50 ng/mL).We further estimate the significance of the effects on other mutational features of these mechanisms(i.e.,transversions,structural variations,and mutation spectrum)in E.coli using linear models.The SOS response plays a positive role in all three mutational features(mutation rates of BPSs,transversions,structural variations)and affects the mutational spectrum.The repair systems significantly reduce the BPS mutation rate and the transversion rate,regardless of whether antibiotics are present,while significantly increasing the structural variation rate in E.coli.Our results quantitatively disentangle the contributions of the SOS response and DNA repair systems in antibiotic-induced mutagenesis.