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Here, we sought to study the transcriptional circuit of HutC, a regulator of both metabolic and virulence genes of the facultative intracellular pathogen <jats:italic>Brucella<\/jats:italic>. Using <jats:italic>in silico<\/jats:italic> and biochemical approaches, we identified a novel functional HutC\u2010binding site upstream of <jats:italic>btaE<\/jats:italic>, a trimeric\u2010autotransporter adhesin involved in the attachment of <jats:italic>Brucella<\/jats:italic> to host extracellular matrix components. Moreover, we identified two additional regulators, one of which, MdrA, acts in concert with HutC to exert a combinatorial control of both <jats:italic>btaE<\/jats:italic> promoter activity and attachment of <jats:italic>Brucella<\/jats:italic> to HeLa cells. Analysis of <jats:italic>btaE<\/jats:italic> promoter sequences of different species indicated that this HutC\u2010binding site was generated <jats:italic>de novo<\/jats:italic> by a single point mutation in a virulent <jats:italic>Brucella<\/jats:italic> strain, indicative of a transcriptional rewiring event. In addition to major domain organization differences existing between BtaE proteins within the genus <jats:italic>Brucella<\/jats:italic>, our analyses revealed that sequences upstream of <jats:italic>btaE<\/jats:italic> display high variability probably associated to intrinsic promoter structural features, which may serve as a substrate for reciprocal selection during co\u2010evolution between this pathogen and its mammalian host.<\/jats:p>","DOI":"10.1111\/mmi.13576","type":"journal-article","created":{"date-parts":[[2016,11,16]],"date-time":"2016-11-16T16:06:30Z","timestamp":1479312390000},"page":"553-565","source":"Crossref","is-referenced-by-count":14,"title":["Combinatorial control of adhesion of <scp><i>B<\/i><\/scp><i>rucella abortus<\/i> 2308 to host cells by transcriptional rewiring of the trimeric autotransporter <i>bta<\/i><scp><i>E<\/i><\/scp> gene"],"prefix":"10.1111","volume":"103","author":[{"given":"Rodrigo","family":"Sieira","sequence":"first","affiliation":[{"name":"Fundaci\u00f3n Instituto Leloir Av. Patricias Argentinas 435 Buenos Aires C1405BWE Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magal\u00ed G.","family":"Bialer","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n Instituto Leloir Av. Patricias Argentinas 435 Buenos Aires C1405BWE Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mara S.","family":"Roset","sequence":"additional","affiliation":[{"name":"IIB\u2010INTECH, CONICET\u2010UNSAM San Mart\u00edn 1650 Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ver\u00f3nica","family":"Ruiz\u2010Ranwez","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n Instituto Leloir Av. Patricias Argentinas 435 Buenos Aires C1405BWE Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom\u00e1s","family":"Langer","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n Instituto Leloir Av. 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