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Bacterial Regulon Evolution: Distinct Responses and Roles for the Identical OmpR Proteins of Typhimurium and in the Acid Stress Response


Salmonella Typhimurium is closely related to Escherichia coli and they possess identical OmpR DNA binding proteins. S. Typhimurium uses OmpR to control the expression of genes involved in adaptation to acid rather than osmotic stress. OmpR expression increases in response to acid stress in S. Typhimurium but not in E. coli due to structural differences in the ompR regulatory region. S. Typhimurium OmpR controls many genes, few of which are in E. coli. Many OmpR-regulated S. Typhimurium-specific targets have been acquired by horizontal gene transfer and contribute to pathogenesis. During infection, S. Typhimurium adapts to the macrophage vacuole, an acidic niche where S. Typhimurium DNA becomes relaxed. DNA relaxation accompanies acid stress in S. Typhimurium but not E. coli and enhances OmpR binding to DNA. Drug-induced DNA relaxation mimics the effect of acid stress on OmpR binding to DNA. Thus acid-sensitive OmpR activity in S. Typhimurium allows OmpR to control many S. Typhimurium-specific genes through a mechanism that depends on changes to DNA topology. We propose that this allosteric role for DNA, combined with a weak requirement on the part of OmpR for binding site sequence specificity, accommodates flexibility in regulon membership and facilitates bacterial evolution.


Vyšlo v časopise: Bacterial Regulon Evolution: Distinct Responses and Roles for the Identical OmpR Proteins of Typhimurium and in the Acid Stress Response. PLoS Genet 10(3): e32767. doi:10.1371/journal.pgen.1004215
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004215

Souhrn

Salmonella Typhimurium is closely related to Escherichia coli and they possess identical OmpR DNA binding proteins. S. Typhimurium uses OmpR to control the expression of genes involved in adaptation to acid rather than osmotic stress. OmpR expression increases in response to acid stress in S. Typhimurium but not in E. coli due to structural differences in the ompR regulatory region. S. Typhimurium OmpR controls many genes, few of which are in E. coli. Many OmpR-regulated S. Typhimurium-specific targets have been acquired by horizontal gene transfer and contribute to pathogenesis. During infection, S. Typhimurium adapts to the macrophage vacuole, an acidic niche where S. Typhimurium DNA becomes relaxed. DNA relaxation accompanies acid stress in S. Typhimurium but not E. coli and enhances OmpR binding to DNA. Drug-induced DNA relaxation mimics the effect of acid stress on OmpR binding to DNA. Thus acid-sensitive OmpR activity in S. Typhimurium allows OmpR to control many S. Typhimurium-specific genes through a mechanism that depends on changes to DNA topology. We propose that this allosteric role for DNA, combined with a weak requirement on the part of OmpR for binding site sequence specificity, accommodates flexibility in regulon membership and facilitates bacterial evolution.


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