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morbidity. Disease development and its manifestations are associated with both host and fungal factors. Concerning the latter, several recent studies have employed the methodology of gene modulation in\n            <jats:italic>P.\u00a0brasiliensis<\/jats:italic>\n            using antisense RNA (AsRNA) and\n            <jats:italic>Agrobacterium tumefaciens<\/jats:italic>\n            -mediated transformation (ATMT) to identify proteins that influence fungus virulence. Our previous observations suggested that paracoccin (PCN), a multidomain fungal protein with both lectin and enzymatic activities, may be a potential\n            <jats:italic>P.\u00a0brasiliensis<\/jats:italic>\n            virulence factor. To explore this, we used AsRNA and ATMT methodology to obtain three independent PCN-silenced\n            <jats:italic>P.\u00a0brasiliensis<\/jats:italic>\n            yeast strains (As\n            <jats:italic>PCN1<\/jats:italic>\n            , As\n            <jats:italic>PCN2<\/jats:italic>\n            , and As\n            <jats:italic>PCN3<\/jats:italic>\n            ) and characterized them with regard to\n            <jats:italic>P.\u00a0brasiliensis<\/jats:italic>\n            biology and pathogenicity. As\n            <jats:italic>PCN1<\/jats:italic>\n            , As\n            <jats:italic>PCN2<\/jats:italic>\n            , and As\n            <jats:italic>PCN3<\/jats:italic>\n            showed relative PCN expression levels that were 60%, 40%, and 60% of that of the wild-type (WT) strain, respectively. PCN silencing led to the aggregation of fungal cells, blocked the morphological yeast-to-mycelium transition, and rendered the yeast less resistant to macrophage fungicidal activity. In addition, mice infected with As\n            <jats:italic>PCN1<\/jats:italic>\n            , As\n            <jats:italic>PCN2<\/jats:italic>\n            , and As\n            <jats:italic>PCN3<\/jats:italic>\n            showed a reduction in fungal burden of approximately 96% compared with those inoculated with the WT strain, which displayed a more extensive destruction of lung tissue. Finally, mice infected with the PCN-silenced yeast strains had lower mortality than those infected with the WT strain. These data demonstrate that PCN acts as a\n            <jats:italic>P.\u00a0brasiliensis<\/jats:italic>\n            contributory virulence factor directly affecting fungal pathogenesis.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            The nonexistence of efficient genetic transformation systems has hampered studies in the dimorphic fungus\n            <jats:italic>Paracoccidioides brasiliensis<\/jats:italic>\n            , the etiological agent of the most frequent systemic mycosis in Latin America. The recent development of a method for gene expression knockdown by antisense RNA technology, associated with an\n            <jats:italic>Agrobacterium tumefaciens<\/jats:italic>\n            -mediated transformation system, provides new strategies for studying\n            <jats:italic>P.\u00a0brasiliensis<\/jats:italic>\n            . Through this technology, we generated yeasts that were silenced for paracoccin (PCN), a\n            <jats:italic>P.\u00a0brasiliensis<\/jats:italic>\n            component that has lectin and enzymatic properties. By comparing the phenotypes of PCN-silenced and wild-type strains of\n            <jats:italic>P.\u00a0brasiliensis<\/jats:italic>\n            , we identified PCN as a virulence factor whose absence renders the yeasts unable to undergo the transition to mycelium and causes a milder pulmonary disease in mice, with a lower mortality rate. Our report highlights the importance of the technology used for\n            <jats:italic>P.\u00a0brasiliensis<\/jats:italic>\n            transformation and demonstrates that paracoccin is a virulence factor acting on fungal biology and pathogenesis.\n          <\/jats:p>","DOI":"10.1128\/mbio.00537-17","type":"journal-article","created":{"date-parts":[[2017,7,19]],"date-time":"2017-07-19T00:10:19Z","timestamp":1500423019000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":20,"title":["Impact of Paracoccin Gene Silencing on\n            <i>Paracoccidioides brasiliensis<\/i>\n            Virulence"],"prefix":"10.1128","volume":"8","author":[{"given":"Fabr\u00edcio F.","family":"Fernandes","sequence":"first","affiliation":[{"name":"Department of Cellular and Molecular Biology, Ribeir\u00e3o Preto School of Medicine, University of S\u00e3o Paulo, Ribeir\u00e3o Preto, S\u00e3o Paulo, Brazil"}]},{"given":"Aline F.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology, Ribeir\u00e3o Preto School of Medicine, University of S\u00e3o Paulo, Ribeir\u00e3o Preto, S\u00e3o Paulo, Brazil"}]},{"given":"Taise N.","family":"Landgraf","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, School of Medicine of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Ribeir\u00e3o Preto, S\u00e3o Paulo, Brazil"}]},{"given":"Cristina","family":"Cunha","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, Braga, Portugal"}]},{"given":"Agostinho","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2014PT Government Associate Laboratory, Braga, Portugal"}]},{"given":"Patr\u00edcia E.","family":"Vendruscolo","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology, Ribeir\u00e3o Preto School of Medicine, University of S\u00e3o Paulo, Ribeir\u00e3o Preto, S\u00e3o Paulo, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3037-3663","authenticated-orcid":false,"given":"Relber A.","family":"Gon\u00e7ales","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology, Ribeir\u00e3o Preto School of Medicine, University of S\u00e3o Paulo, Ribeir\u00e3o Preto, S\u00e3o Paulo, Brazil"}]},{"given":"Fausto","family":"Almeida","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, School of Medicine of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Ribeir\u00e3o Preto, S\u00e3o Paulo, Brazil"}]},{"given":"Thiago A.","family":"da 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