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SpxA1 and SpxA2 interact with RNA polymerase (RNAP) to activate the transcription of genes implicated in the prevention and alleviation of oxidative protein damage. The\n            <jats:italic>spxA2<\/jats:italic>\n            gene is highly upregulated in infected macrophages, but how this is achieved is unknown. Previous studies have shown that the\n            <jats:italic>spxA2<\/jats:italic>\n            gene was under negative control by the Rrf2 family repressor protein, SaiR, whose activity is sensitive to oxidative stress. These studies also suggested that\n            <jats:italic>spxA2<\/jats:italic>\n            was under positive autoregulation. In the present study, we show by\n            <jats:italic>in vivo<\/jats:italic>\n            and\n            <jats:italic>in vitro<\/jats:italic>\n            analyses that\n            <jats:italic>spxA2<\/jats:italic>\n            is under direct autoregulation but is also dependent on the SpxA1 paralogous protein. The deletion of either\n            <jats:italic>spxA1<\/jats:italic>\n            or\n            <jats:italic>spxA2<\/jats:italic>\n            reduced the diamide-inducible expression of an\n            <jats:italic>spxA2-lacZ<\/jats:italic>\n            construct.\n            <jats:italic>In vitro<\/jats:italic>\n            transcription reactions using purified\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. anthracis<\/jats:named-content>\n            RNAP showed that SpxA1 and SpxA2 protein stimulates transcription from a DNA fragment containing the\n            <jats:italic>spxA2<\/jats:italic>\n            promoter. Ectopically positioned\n            <jats:italic>spxA2-lacZ<\/jats:italic>\n            fusion requires both SpxA1 and SpxA2 for expression, but the requirement for SpxA1 is partially overcome when\n            <jats:italic>saiR<\/jats:italic>\n            is deleted. Electrophoretic mobility shift assays showed that SpxA1 and SpxA2 enhance the affinity of RNAP for\n            <jats:italic>spxA2<\/jats:italic>\n            promoter DNA and that this activity is sensitive to reductant. We hypothesize that the previously observed upregulation of\n            <jats:italic>spxA2<\/jats:italic>\n            in the oxidative environment of the macrophage is at least partly due to SpxA1-mediated SaiR repressor inactivation and the positive autoregulation of\n            <jats:italic>spxA2<\/jats:italic>\n            transcription.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Regulators of transcription initiation are known to govern the expression of genes required for virulence in pathogenic bacterial species. Members of the Spx family of transcription factors function in control of genes required for virulence and viability in low-GC Gram-positive bacteria. In\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Bacillus anthracis<\/jats:named-content>\n            , the\n            <jats:italic>spxA2<\/jats:italic>\n            gene is highly induced in infected macrophages, which suggests an important role in the control of virulence gene expression during the anthrax disease state. We provide evidence that elevated concentrations of oxidized, active SpxA2 result from an autoregulatory positive-feedback loop driving\n            <jats:italic>spxA2<\/jats:italic>\n            transcription.\n          <\/jats:p>","DOI":"10.1128\/jb.00512-16","type":"journal-article","created":{"date-parts":[[2016,8,9]],"date-time":"2016-08-09T03:03:15Z","timestamp":1470711795000},"page":"2902-2913","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["Evidence that Oxidative Stress Induces\n            <i>spxA2<\/i>\n            Transcription in Bacillus anthracis Sterne through a Mechanism Requiring SpxA1 and Positive Autoregulation"],"prefix":"10.1128","volume":"198","author":[{"given":"Skye","family":"Barendt","sequence":"first","affiliation":[{"name":"Institute of Environmental Health, Oregon Health and Science University, Portland, Oregon, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cierra","family":"Birch","sequence":"additional","affiliation":[{"name":"Institute of Environmental Health, Oregon Health and Science University, Portland, Oregon, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lea","family":"Mbengi","sequence":"additional","affiliation":[{"name":"Institute of Environmental Health, Oregon Health and Science University, Portland, Oregon, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Zuber","sequence":"additional","affiliation":[{"name":"Institute of Environmental Health, Oregon Health and Science University, Portland, Oregon, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2006.01.005"},{"key":"e_1_3_3_3_2","first-page":"101","article-title":"MarA, SoxS, and Rob of Escherichia coli: global regulators of multidrug resistance, virulence, and stress response","volume":"2","author":"Duval V","year":"2013","unstructured":"Duval V, Lister IM. 2013. 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