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

作　　者：Tongtong Lin Jiao Pan Colin Gregory Yaohai Wang Clayton Tincher Caitlyn Rivera Michael Lynch Hongan Long Yu Zhang 

机构地区：[1]Institute of Evolution and Marine Biodiversity,KLMME,Ocean University of China,Qingdao 266003,China [2]Laboratory for Marine Biology and Biotechnology,Laoshan Laboratory,Qingdao 266237,China [3]Department of Biology,Indiana University,Bloomington 47405,USA [4]Biodesign Center for Mechanisms of Evolution,Arizona State University,Tempe 85281,USA [5]School of Mathematics Science,Ocean University of China,Qingdao 266000,China

出　　处：《Marine Life Science & Technology》2023年第4期538-550,共13页海洋生命科学与技术（英文）

基　　金：supported by Laoshan Laboratory(LSKJ202203203);the National Natural Science Foundation of China(31961123002,32270435);the Fundamental Research Funds for the Central Universities(202161064);the Young Taishan Scholars Program of Shandong Province(tsqn201812024);the Natural Science Foundation of Shandong Province(ZR2023QC191);the National Institutes of Health award(R35-GM122566).

摘　　要：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.

关 键 词：Stress response Antibiotic-induced mutagenesis Mutation spectrum Linear model 

分 类 号：R378.21[医药卫生—病原生物学] R978.1[医药卫生—基础医学]