Amino Acid Permeases and Virulence in Cryptococcus neoformans

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dc.citation.issue10
dc.citation.volume11
dc.contributor.authorMartho, Kevin Felipe Cruz [UNIFESP]
dc.contributor.authorMelo, Amanda Teixeira de [UNIFESP]
dc.contributor.authorFernandes Takahashi, Juliana Possato
dc.contributor.authorGuerra, Juliana Mariotti
dc.contributor.authorda Silva Santos, Dayane Cristina
dc.contributor.authorPurisco, Sonia Ueda
dc.contributor.authorCarvalho Melhem, Marcia de Souza
dc.contributor.authorFazioli, Raquel dos Anjos
dc.contributor.authorPhanord, Clerlune [UNIFESP]
dc.contributor.authorSartorelli, Patricia [UNIFESP]
dc.contributor.authorVallim, Marcelo Afonso [UNIFESP]
dc.contributor.authorPascon, Renata Castiglioni [UNIFESP]
dc.coverageSan Francisco
dc.date.accessioned2020-07-31T12:47:35Z
dc.date.available2020-07-31T12:47:35Z
dc.date.issued2016
dc.description.abstractFungal opportunistic pathogens colonize various environments, from plants and wood to human and animal tissue. Regarding human pathogens, one great challenge during contrasting niche occupation is the adaptation to different conditions, such as temperature, osmolarity, salinity, pressure, oxidative stress and nutritional availability, which may constitute sources of stress that need to be tolerated and overcome. As an opportunistic pathogen, C. neoformans faces exactly these situations during the transition from the environment to the human host, encountering nutritional constraints. Our previous and current research on amino acid biosynthetic pathways indicates that amino acid permeases are regulated by the presence of the amino acids, nitrogen and temperature. Saccharomyces cerevisiae and Candida albicans have twenty-four and twenty-seven genes encoding amino acid permeases, respectivelyen
dc.description.abstractconversely, they are scarce in number in Basidiomycetes (C. neoformans, Coprinopsis cinerea and Ustilago maydis), where nine to ten permease genes can be found depending on the species. In this study, we have demonstrated that two amino acid permeases are essential for virulence in C. neoformans. Our data showed that C. neoformans uses two global and redundant amino acid permeases, Aap4 and Aap5 to respond correctly to thermal and oxidative stress. Double deletion of these permeases causes growth arrest in C. neoformans at 37 degrees C and in the presence of hydrogen peroxide. The inability to uptake amino acid at a higher temperature and under oxidative stress also led to virulence attenuation in vivo. Our data showed that thermosensitivity caused by the lack of permeases Aap4 and Aap5 can be remedied by alkaline conditions (higher pH) and salinity. Permeases Aap4 and Aap5 are also required during fluconazole stress and they are the target of the plant secondary metabolite eugenol, a potent antifungal inhibitor that targets amino acid permeases. In summary, our work unravels (i) interesting physiological property of C. neoformans regarding its amino acid uptake systemen
dc.description.abstract(ii) an important aspect of virulence, which is the need for amino acid permeases during thermal and oxidative stress resistance and, hence, host invasion and colonizationen
dc.description.abstractand (iii) provides a convenient prototype for antifungal development, which are the amino acid permeases Aap4/Aap5 and their inhibitor.en
dc.description.affiliationUniv Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Rua Arthur Ridel 275, Diadema, SP, Brazil
dc.description.affiliationAdolfo Lutz Inst, Quantitat Pathol Unit, Sao Paulo, Brazil
dc.description.affiliationSecretary Hlth, Adolfo Lutz Inst, Mycol Unit, Sao Paulo, Brazil
dc.description.affiliationUnifespInstituto de Ciências Ambientais, Química e Farmacêuticas, Universidade Federal de São Paulo, Rua Arthur Ridel, 275, Diadema, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipIDFAPESP: 2011/51298-4
dc.description.sponsorshipIDFAPESP: 2015/04400-9
dc.format.extent-
dc.identifierhttp://dx.doi.org/10.1371/journal.pone.0163919
dc.identifier.citationPlos One. San Francisco, v. 11, n. 10, p. -, 2016.
dc.identifier.doi10.1371/journal.pone.0163919
dc.identifier.fileWOS000385553100065.pdf
dc.identifier.issn1932-6203
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/56915
dc.identifier.wosWOS:000385553100065
dc.language.isoeng
dc.publisherPublic Library Science
dc.relation.ispartofPlos One
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleAmino Acid Permeases and Virulence in Cryptococcus neoformansen
dc.typeinfo:eu-repo/semantics/article
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