{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T03:02:03Z","timestamp":1767927723190,"version":"3.49.0"},"reference-count":34,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2012,5,24]],"date-time":"2012-05-24T00:00:00Z","timestamp":1337817600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Yeast"],"published-print":{"date-parts":[[2012,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Paracoccidioides brasiliensis<\/jats:italic> is the agent of paracoccidioidomycosis, the most prevalent deep mycosis in Latin America. The production of eicosanoids during fungal infection has been associated with the biology of these microorganisms and modulation of host immune response. The aim of our study was to evaluate whether <jats:italic>P. brasiliensis<\/jats:italic> strains with high or low virulence produce leukotriene B4 (LTB<jats:sub>4<\/jats:sub>), using endogenous and\/or exogenous sources of arachidonic acid (AA). Moreover, we assessed whether this fungus might use the same metabolic pathway, described for mammalian cells, that involves the lipoxygenase (LOX) enzyme. The association between the production of this eicosanoid and fungus survival and growth was also evaluated. Our results showed that <jats:italic>P. brasiliensis<\/jats:italic>, irrespective of its virulence, produces high levels of LTB<jats:sub>4<\/jats:sub> using endogenous AA. In addition, in cultures treated with exogenous AA, LTB<jats:sub>4<\/jats:sub> levels were significantly higher, showing that this fungus also uses exogenous sources of fatty acids. Treatment with MK886, which blocks the activity of lipoxygenase, by inhibiting five\u2010lipoxygenase\u2010activating protein (FLAP) or with nordihydroguaiaretic acid (NDGA), a non\u2010selective lipoxygenase inhibitor, resulted in a significant reduction in LTB<jats:sub>4<\/jats:sub> levels, indicating that the fungus produces this eicosanoid by using the LOX pathway or an enzyme with biochemically similar function. The significant reduction in viability detected in cultures treated with these inhibitors was, however, restored by adding exogenous LTB<jats:sub>4<\/jats:sub>, confirming the role of this eicosanoid in fungus survival. Moreover, the addition of LTB<jats:sub>4<\/jats:sub> to cultures capable of producing LTs induces fungal growth. These results provide a foundation for additional studies on the contributions of LTB<jats:sub>4<\/jats:sub> in <jats:italic>P. brasiliensis<\/jats:italic> virulence. Copyright \u00a9 2012 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/yea.2900","type":"journal-article","created":{"date-parts":[[2012,4,12]],"date-time":"2012-04-12T02:58:34Z","timestamp":1334199514000},"page":"201-208","source":"Crossref","is-referenced-by-count":9,"title":["Production of leukotriene B<sub>4<\/sub> by <i>Paracoccidioides brasiliensis<\/i>"],"prefix":"10.1002","volume":"29","author":[{"given":"Guilherme Augusto","family":"Biondo","sequence":"first","affiliation":[{"name":"Departamento de Microbiologia e Imunologia Universidade Estadual Paulista (UNESP)  Campus de Botucatu SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciane Alarc\u00e3o","family":"Dias\u2010Melicio","sequence":"additional","affiliation":[{"name":"Departamento de Patologia Universidade Estadual Paulista (UNESP)  Campus de Botucatu SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Paula","family":"Bordon\u2010Graciani","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia e Imunologia Universidade Estadual Paulista (UNESP)  Campus de Botucatu SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cilmery Suemi","family":"Kurokawa","sequence":"additional","affiliation":[{"name":"Departamento de Pediatria Universidade Estadual Paulista (UNESP)  Campus de Botucatu SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela Maria Victoriano","family":"de Campos Soares","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia e Imunologia Universidade Estadual Paulista (UNESP)  Campus de Botucatu SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,5,24]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0074-02762010000700005"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11046-010-9301-x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2007.02.019"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11046-007-0098-1"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1100\/tsw.2007.180"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.6.2.89"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/13693780500536885"},{"key":"e_1_2_6_9_1","doi-asserted-by":"crossref","first-page":"3138","DOI":"10.1128\/iai.62.8.3138-3145.1994","article-title":"Candida albicans stimulates aracidonic acid liberation from alveolar macrophages through \u03b1\u2010mannan and \u03b2\u2010glucan cell wall components","volume":"62","author":"Castro M","year":"1994","journal-title":"Infect. 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