The role of Aspartyl aminopeptidase (Ape4) in Cryptococcus neoformans virulence and authophagy

Página do item simplificado
dc.citation.issue5
dc.citation.volume12
dc.contributor.authorGontijo, Fabiano de Assis [UNIFESP]
dc.contributor.authorde Melo, Amanda Teixeira [UNIFESP]
dc.contributor.authorPascon, Renata C. [UNIFESP]
dc.contributor.authorFernandes, Larissa
dc.contributor.authorPaes, Hugo Costa
dc.contributor.authorAlspaugh, J. Andrew
dc.contributor.authorVallim, Marcelo A. [UNIFESP]
dc.coverageSan Francisco
dc.date.accessioned2020-07-13T11:53:12Z
dc.date.available2020-07-13T11:53:12Z
dc.date.issued2017
dc.description.abstractIn order to survive and cause disease, microbial pathogens must be able to proliferate at the temperature of their infected host. We identified novel microbial features associated with thermotolerance in the opportunistic fungal pathogen Cryptococcus neoformans using a random insertional mutagenesis strategy, screening for mutants with defective growth at 37 degrees C. Among several thermosensitive mutants, we identified one bearing a disruption in a gene predicted to encode the Ape4 aspartyl aminopeptidase protein. Ape4 metalloproteases in other fungi, including Saccharomyces cerevisiae, are activated by nitrogen starvation, and they are required for autophagy and the cytoplasm-to-vacuole targeting (Cvt) pathway. However, none have been previously associated with altered growth at elevated temperatures. We demonstrated that the C. neoformans ape4 mutant does not grow at 37 degrees C, and it also has defects in the expression of important virulence factors such as phospholipase production and capsule formation. C. neoformans Ape4 activity was required for this facultative intracellular pathogen to survive within macrophages, as well as for virulence in an animal model of cryptococcal infection. Similar to S. cerevisiae Ape4, the C. neoformans GFP-Ape4 fusion protein co-localized with intracytoplasmic vesicles during nitrogen depletion. APE4 expression was also induced by the combination of nutrient and thermal stress. Together these results suggest that autophagy is an important cellular process for this microbial pathogen to survive within the environment of the infected host.en
dc.description.affiliationUniv Fed Sao Paulo, Dept Ciencias Biol, Diadema, SP, Brazil
dc.description.affiliationUniv Brasilia, Fac Ceilandia, Ceilandia, DF, Brazil
dc.description.affiliationUniv Brasilia, Fac Med, Brasilia, DF, Brazil
dc.description.affiliationDuke Univ, Sch Med, Dept Med, Durham, NC 27706 USA
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Ciencias Biol, Diadema, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFAPESP
dc.description.sponsorshipNIH
dc.description.sponsorshipIDFAPESP: 2007/50536-3
dc.description.sponsorshipIDFAPESP: 2015/04400-9
dc.description.sponsorshipIDFAPESP: 2011/51298-4
dc.description.sponsorshipIDFAPESP: 2016/14542-8
dc.description.sponsorshipIDNIH: AI050128
dc.description.sponsorshipIDNIH: AI074677
dc.format.extent-
dc.identifierhttp://dx.doi.org/10.1371/journal.pone.0177461
dc.identifier.citationPlos One. San Francisco, v. 12, n. 5, p. -, 2017.
dc.identifier.doi10.1371/journal.pone.0177461
dc.identifier.fileWOS000402062800017.pdf
dc.identifier.issn1932-6203
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/54450
dc.identifier.wosWOS:000402062800017
dc.language.isoeng
dc.publisherPublic Library Science
dc.relation.ispartofPlos One
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleThe role of Aspartyl aminopeptidase (Ape4) in Cryptococcus neoformans virulence and authophagyen
dc.typeinfo:eu-repo/semantics/article
Arquivos
Coleções
ICAQF - Artigos