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In the present study, we identified a virulence factor involved in the modulation of hepatic stellate cell function and consequent fibrosis during<jats:named-content content-type=\"genus-species\">Brucella abortus<\/jats:named-content>infection. This study assessed the role of BPE005 protein from<jats:named-content content-type=\"genus-species\">B. abortus<\/jats:named-content>in the fibrotic phenotype induced on hepatic stellate cells during<jats:named-content content-type=\"genus-species\">B. abortus<\/jats:named-content>infection<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>. We demonstrated that the fibrotic phenotype induced by<jats:named-content content-type=\"genus-species\">B. abortus<\/jats:named-content>on hepatic stellate (LX-2) cells was dependent on BPE005, a protein associated with the type IV secretion system (T4SS) VirB from<jats:named-content content-type=\"genus-species\">B. abortus<\/jats:named-content>. Our results indicated that<jats:named-content content-type=\"genus-species\">B. abortus<\/jats:named-content>inhibits matrix metalloproteinase 9 (MMP-9) secretion through the activity of the BPE005-secreted protein and induces concomitant collagen deposition by LX-2 cells. BPE005 is a small protein containing a cyclic nucleotide monophosphate binding domain (cNMP) that modulates the LX-2 cell phenotype through a mechanism that is dependent on the cyclic AMP (cAMP)\/protein kinase A (PKA) signaling pathway. Altogether, these results indicate that<jats:named-content content-type=\"genus-species\">B. abortus<\/jats:named-content>tilts LX-2 cells to a profibrogenic phenotype employing a functional T4SS and the secreted BPE005 protein through a mechanism that involves the cAMP and PKA signaling pathway.<\/jats:p>","DOI":"10.1128\/iai.01227-15","type":"journal-article","created":{"date-parts":[[2015,12,15]],"date-time":"2015-12-15T04:24:41Z","timestamp":1450153481000},"page":"598-606","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":24,"title":["The Effector Protein BPE005 from Brucella abortus Induces Collagen Deposition and Matrix Metalloproteinase 9 Downmodulation via Transforming Growth Factor \u03b21 in Hepatic Stellate Cells"],"prefix":"10.1128","volume":"84","author":[{"given":"Paula Constanza","family":"Arriola Benitez","sequence":"first","affiliation":[{"name":"Instituto de Inmunolog\u00eda, Gen\u00e9tica y Metabolismo (INIGEM), Hospital de Cl\u00ednicas Jos\u00e9 de San Mart\u00edn, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Rey Serantes","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biotecnol\u00f3gicas Dr. Rodolfo A. 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