Browsing by Author "Feng, Youjun"

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    Mutation-induced remodeling of the BfmRS two-component system in Pseudomonas aeruginosa clinical isolates
    (AAAS, 2020-11) 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; Microbiology and Immunology, School of Medicine
    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.