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It is responsible for a high degree of mortality and is invariably unresponsive to conventional antifungal treatments. Histone deacetylase inhibitors can affect the cell cycle, apoptosis and differentiation. The histone deacetylase inhibitor vorinostat (SAHA) has recently received approval for the treatment of cutaneous T cell lymphoma. Here, we investigated the interactions of SAHA and itraconazole, voriconazole, and posaconazole against\n                      <jats:italic>Aspergillus<\/jats:italic>\n                      spp\n                      <jats:italic>.<\/jats:italic>\n                      in vitro using both planktonic cells and biofilms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We investigated 20 clinical strains using broth microdilution checkerboard methods. The results showed synergy between SAHA and itraconazole, voriconazole, and posaconazole against 60, 40, and 25% of tested isolates of planktonic\n                      <jats:italic>Aspergillus<\/jats:italic>\n                      spp., respectively. Similar synergy was also observed against\n                      <jats:italic>Aspergillus<\/jats:italic>\n                      biofilms. The expression of the azole-associated multidrug efflux pumps\n                      <jats:italic>MDR1<\/jats:italic>\n                      ,\n                      <jats:italic>MDR2<\/jats:italic>\n                      ,\n                      <jats:italic>MDR3<\/jats:italic>\n                      and\n                      <jats:italic>MDR4,<\/jats:italic>\n                      as well as that of\n                      <jats:italic>HSP90,<\/jats:italic>\n                      was measured by RT-PCR. The results indicated that the molecular mechanism of the observed synergistic effects in\n                      <jats:italic>Aspergillus fumigatus<\/jats:italic>\n                      may be partly associated with dampened expression of the efflux pump genes and, furthermore, that\n                      <jats:italic>HSP90<\/jats:italic>\n                      suppression may be a major contributor to the observed synergistic effects of the drugs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      SAHA has potential as a secondary treatment to enhance the effects of azoles against both biofilm and planktonic cells of\n                      <jats:italic>Aspergillus<\/jats:italic>\n                      spp\n                      <jats:italic>.<\/jats:italic>\n                      in vitro\n                      <jats:italic>.<\/jats:italic>\n                      This effect occurs mostly by inhibition of\n                      <jats:italic>HSP90<\/jats:italic>\n                      expression.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12866-020-1718-x","type":"journal-article","created":{"date-parts":[[2020,2,6]],"date-time":"2020-02-06T19:06:38Z","timestamp":1581015998000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Synergistic effects of vorinostat (SAHA) and azoles against Aspergillus species and their biofilms"],"prefix":"10.1186","volume":"20","author":[{"given":"Bo","family":"Tu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gendi","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6261-2630","authenticated-orcid":false,"given":"Hui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,2,7]]},"reference":[{"issue":"4","key":"1718_CR1","doi-asserted-by":"publisher","first-page":"57","DOI":"10.3390\/jof3040057","volume":"3","author":"Felix Bongomin","year":"2017","unstructured":"Bongomin F, Gago S, Oladele RO, Denning DW. 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The authors alone are responsible for the content and writing of the paper.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"28"}}