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Zusammenfassung: <jats:p> To accomplish successful infection, pathogens must operate their virulence programs in a precise, time-sensitive, and coordinated manner. A major question is how pathogens control the timing of virulence gene expression during infection. Here we report that the intracellular pathogen <jats:italic>Salmonella</jats:italic> controls the timing and level of virulence gene expression by using an inhibitory protein, EIIA <jats:sup>Ntr</jats:sup> . A DNA binding master virulence regulator, PhoP, controls various virulence genes inside acidic phagosomes. <jats:italic>Salmonella</jats:italic> decreases EIIA <jats:sup>Ntr</jats:sup> amounts at acidic pH in a Lon- and PhoP-dependent manner. This, in turn, promotes expression of the PhoP-activated virulence program because EIIA <jats:sup>Ntr</jats:sup> hampers activation of PhoP-regulated genes by interfering with PhoP binding to DNA. EIIA <jats:sup>Ntr</jats:sup> enables <jats:italic>Salmonella</jats:italic> to impede the activation of PhoP-regulated gene expression inside macrophages. Our findings suggest that <jats:italic>Salmonella</jats:italic> achieves programmed delay of virulence gene activation by adjusting levels of an inhibitory factor. </jats:p>
ISSN: 2161-2129
2150-7511
DOI: 10.1128/mbio.00291-19