{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T14:41:18Z","timestamp":1768401678102,"version":"3.49.0"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2016,8,1]],"date-time":"2016-08-01T00:00:00Z","timestamp":1470009600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Antimony (Sb) resistance in leishmaniasis chemotherapy has become one of the major challenges to the control of this spreading worldwide public health problem. Since the plasma membrane pore-forming protein aquaglyceroporin 1 (AQP1) is the major route of Sb uptake in<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Leishmania<\/jats:named-content>, functional studies are relevant to characterize drug transport pathways in the parasite. We generated AQP1-overexpressing<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Leishmania guyanensis<\/jats:named-content>and<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">L. braziliensis<\/jats:named-content>mutants and investigated their susceptibility to the trivalent form of Sb (Sb<jats:sup>III<\/jats:sup>) in the presence of silver and nitrate salts. Both AQP1-overexpressing lines presented 3- to 4-fold increased AQP1 expression levels compared with those of their untransfected counterparts, leading to an increased Sb<jats:sup>III<\/jats:sup>susceptibility of about 2-fold. Competition assays using silver nitrate, silver sulfadiazine, or silver acetate prior to Sb<jats:sup>III<\/jats:sup>exposure increased parasite growth, especially in AQP1-overexpressing mutants. Surprisingly, Sb<jats:sup>III<\/jats:sup>-sodium nitrate or Sb<jats:sup>III<\/jats:sup>-potassium nitrate combinations showed significantly enhanced antileishmanial activities compared to those of Sb<jats:sup>III<\/jats:sup>alone, especially against AQP1-overexpressing mutants, suggesting a putative nitrate-dependent modulation of AQP1 activity. The intracellular level of antimony quantified by graphite furnace atomic absorption spectrometry showed that the concomitant exposure to Sb<jats:sup>III<\/jats:sup>and nitrate favors antimony accumulation in the parasite, increasing the toxicity of the drug and culminating with parasite death. This is the first report showing evidence of AQP1-mediated Sb<jats:sup>III<\/jats:sup>susceptibility modulation by silver in<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Leishmania<\/jats:named-content>and suggests the potential antileishmanial activity of the combination of nitrate salts and Sb<jats:sup>III<\/jats:sup>.<\/jats:p>","DOI":"10.1128\/aac.00768-16","type":"journal-article","created":{"date-parts":[[2016,5,10]],"date-time":"2016-05-10T03:05:16Z","timestamp":1462849516000},"page":"4482-4489","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":12,"title":["Silver and Nitrate Oppositely Modulate Antimony Susceptibility through Aquaglyceroporin 1 in Leishmania (Viannia) Species"],"prefix":"10.1128","volume":"60","author":[{"given":"Juvana M.","family":"Andrade","sequence":"first","affiliation":[{"name":"Centro de Pesquisas Ren\u00e9 Rachou, Funda\u00e7\u00e3o Oswaldo Cruz, Belo Horizonte, MG, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elio H.","family":"Baba","sequence":"additional","affiliation":[{"name":"Centro de Pesquisas Ren\u00e9 Rachou, Funda\u00e7\u00e3o Oswaldo Cruz, Belo Horizonte, MG, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo A.","family":"Machado-de-Avila","sequence":"additional","affiliation":[{"name":"Unidade Acad\u00eamica de Ci\u00eancias da Sa\u00fade, Universidade do Extremo Sul Catarinense, Crici\u00fama, SC, Brazil"},{"name":"Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Chavez-Olortegui","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cynthia P.","family":"Demicheli","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Exatas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Fr\u00e9zard","sequence":"additional","affiliation":[{"name":"Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rubens L.","family":"Monte-Neto","sequence":"additional","affiliation":[{"name":"Centro de Pesquisas Ren\u00e9 Rachou, Funda\u00e7\u00e3o Oswaldo Cruz, Belo Horizonte, MG, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvane M. 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