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Mutation-induced remodeling of the BfmRS two-component system in Pseudomonas aeruginosa clinical isolates.
Cao, Qiao; Yang, Nana; Wang, Yanhui; Xu, Chenchen; Zhang, Xue; Fan, Ke; Chen, Feifei; Liang, Haihua; Zhang, Yingchao; Deng, Xin; Feng, Youjun; Yang, Cai-Guang; Wu, Min; Bae, Taeok; Lan, Lefu.
Afiliación
  • Cao Q; College of Life Science, Northwest University, Xi'an 710127, China.
  • Yang N; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Wang Y; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Xu C; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Zhang X; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Fan K; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Chen F; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Liang H; College of Life Science, Northwest University, Xi'an 710127, China.
  • Zhang Y; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Deng X; College of Life Science, Northwest University, Xi'an 710127, China.
  • Feng Y; Department of Biomedical Sciences, City University of Hong Kong, Kowloon Tong, Hong Kong 999077, China.
  • Yang CG; Department of Biomedical Sciences, City University of Hong Kong, Kowloon Tong, Hong Kong 999077, China.
  • Wu M; School of Medicine, Zhejiang University, Hangzhou 310058, China.
  • Bae T; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Lan L; School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, UCAS, Hangzhou 310024, China.
Sci Signal ; 13(656)2020 11 03.
Article en En | MEDLINE | ID: mdl-33144518
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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pseudomonas aeruginosa / Proteínas Bacterianas / Mutación Missense / Histidina Quinasa Límite: Humans Idioma: En Revista: Sci Signal Asunto de la revista: CIENCIA / FISIOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pseudomonas aeruginosa / Proteínas Bacterianas / Mutación Missense / Histidina Quinasa Límite: Humans Idioma: En Revista: Sci Signal Asunto de la revista: CIENCIA / FISIOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos