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标题：Crystal structures of YeiE from Cronobacter sakazakii and the role of sulfite tolerance in gram-negative bacteria
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作者：Seokho Hong ; Jinshil Kim ; Eunshin Cho 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：11
DOI：10.1073/pnas.2118002119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance YeiE has been identified as a master virulence factor of Cronobacter sakazakii. In this study, we determined the crystal structures of the regulatory domain of YeiE in complex with its physiological ligand sulfite ion (SO 3 2−). The structure provides the basis for the molecular mechanisms for sulfite sensing and the ligand-dependent conformational changes of the regulatory domain. The genes under the control of YeiE in response to sulfite were investigated to reveal the functional roles of YeiE in the sulfite tolerance of the bacteria. We propose the molecular mechanism underlying the ability of gram-negative pathogens to defend against the innate immune response involving sulfite, thus providing a strategy to control the pathogenesis of bacteria. Cronobacter sakazakii is an emerging gram-negative pathogenic bacterium that causes meningitis, bacteremia, and necrotizing enterocolitis in infants and has a high mortality rate. The YeiE homolog (gpESA_01081) was identified as a global virulence regulator of bacterial pathogenesis in C. sakazakii. YeiE is a LysR-type transcriptional regulator (LTTR) composed of a DNA binding domain and a regulatory domain to recognize the unknown ligand. To reveal the molecular mechanism and function of YeiE, we determined the crystal structure of the regulatory domain of YeiE. A sulfite ion was bound at the putative ligand-binding site, and subsequent studies revealed that the sulfite is the physiological ligand for YeiE. Structural comparisons to its sulfite-free structure further showed the sulfite-dependent conformational change of YeiE. The essential role of YeiE in defending against toxicity from sulfite during the growth of C. sakazakii and Escherichia coli was examined. Furthermore, the target genes and functional roles of YeiE in H 2S production and survival capability from neutrophils were investigated. Our findings provide insights into the sophisticated behaviors of pathogenic gram-negative bacteria in response to sulfite from the environment and host.
关键词：enYeiELysR-type transcriptional regulatorsulfitehydrogen sulfidesulfite reductase