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Mutation-induced remodeling of the BfmRS two-component system in Pseudomonas aeruginosa clinical isolates
Cao, Qiao1,3; Yang, Nana1; Wang, Yanhui1; Xu, Chenchen1; Zhang, Xue1; Fan, Ke1; Chen, Feifei1,3; Liang, Haihua3; Zhang, Yingchao2; Deng, Xin2
刊名SCIENCE SIGNALING
2020-11-03
卷号13期号:656页码:21
ISSN号1945-0877
DOI10.1126/scisignal.aaz1529
通讯作者Lan, Lefu(llan@simm.ac.cn)
英文摘要Genetic mutations are a primary driving force behind the adaptive evolution of bacterial pathogens. Multiple clinical isolates of Pseudomonas aeruginosa, an important human pathogen, have naturally evolved one or more missense mutations in bfmS, which encodes the sensor histidine kinase of the BfmRS two-component system (TCS). A mutant BfmS protein containing both the L181P and E376Q substitutions increased the phosphorylation and thus the transcriptional regulatory activity of its cognate downstream response regulator, BfmR. This reduced acute virulence and enhanced biofilm formation, both of which are phenotypic changes associated with a chronic infection state. The increased phosphorylation of BfmR was due, at least in part, to the cross-phosphorylation of BfmR by GtrS, a noncognate sensor kinase. Other spontaneous missense mutations in bfmS, such as A42E/G347D, T242R, and R393H, also caused a similar remodeling of the BfmRS TCS in P. aeruginosa. This study highlights the plasticity of TCSs mediated by spontaneous mutations and suggests that mutation-induced activation of BfmRS may contribute to host adaptation by P. aeruginosa during chronic infections.
资助项目National Natural Science Foundation (NSFC)[31670136] ; National Natural Science Foundation (NSFC)[31870127] ; National Natural Science Foundation (NSFC)[81861138047] ; Ministry of Science and Technology (MOST)[2016YFA0501503] ; Ministry of Science and Technology (MOST)[2019ZX09721001-004-003] ; Science and Technology Commission of Shanghai Municipality[19JC1416400]
WOS关键词HOST-RANGE PLASMIDS ; RESPONSE REGULATOR ; GLUCOSE ABNORMALITIES ; BACTERIAL ADAPTATION ; ESCHERICHIA-COLI ; GENE-EXPRESSION ; YOUNG-CHILDREN ; DELETION ; PHOSPHORYLATION ; SPECIFICITY
WOS研究方向Biochemistry & Molecular Biology ; Cell Biology
语种英语
出版者AMER ASSOC ADVANCEMENT SCIENCE
WOS记录号WOS:000587410500001
内容类型期刊论文
源URL[http://119.78.100.183/handle/2S10ELR8/292585]  
专题中国科学院上海药物研究所
通讯作者Lan, Lefu
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
2.City Univ Hong Kong, Dept Biomed Sci, Kowloon Tong, Hong Kong 999077, Peoples R China
3.Northwest Univ, Coll Life Sci, Xian 710127, Peoples R China
4.Zhejiang Univ, Sch Med, Hangzhou 310058, Peoples R China
5.UCAS, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China
6.Univ North Dakota, Dept Biomed Sci, Grand Forks, ND 58203 USA
7.Indiana Univ Sch Med, Dept Microbiol & Immunol, Gary, IN 46408 USA
8.Shanghai Inst Food & Drug Control, NMPA Key Lab Testing Technol Pharmaceut Microbiol, Shanghai, Peoples R China
推荐引用方式
GB/T 7714
Cao, Qiao,Yang, Nana,Wang, Yanhui,et al. Mutation-induced remodeling of the BfmRS two-component system in Pseudomonas aeruginosa clinical isolates[J]. SCIENCE SIGNALING,2020,13(656):21.
APA Cao, Qiao.,Yang, Nana.,Wang, Yanhui.,Xu, Chenchen.,Zhang, Xue.,...&Lan, Lefu.(2020).Mutation-induced remodeling of the BfmRS two-component system in Pseudomonas aeruginosa clinical isolates.SCIENCE SIGNALING,13(656),21.
MLA Cao, Qiao,et al."Mutation-induced remodeling of the BfmRS two-component system in Pseudomonas aeruginosa clinical isolates".SCIENCE SIGNALING 13.656(2020):21.
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