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Capsule growth in Cryptococcus neoformans is coordinated with cell cycle progression

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dc.contributor.authorGarcia-Rodas, Rocio
dc.contributor.authorCordero, Radames J B
dc.contributor.authorTrevijano-Contador, Nuria
dc.contributor.authorJanbon, Guilhem
dc.contributor.authorMoyrand, Frédérique
dc.contributor.authorCasadevall, Arturo
dc.contributor.authorZaragoza, Oscar
dc.contributor.funderMinisterio de Economía y Competitividad (España)
dc.contributor.funderMinisterio de Ciencia e Innovación (España)
dc.date.accessioned2020-02-21T12:44:07Z
dc.date.available2020-02-21T12:44:07Z
dc.date.issued2014-06-17
dc.description.abstractUNLABELLED: The fungal pathogen Cryptococcus neoformans has several virulence factors, among which the most important is a polysaccharide capsule. The size of the capsule is variable and can increase significantly during infection. In this work, we investigated the relationship between capsular enlargement and the cell cycle. Capsule growth occurred primarily during the G1 phase. Real-time visualization of capsule growth demonstrated that this process occurred before the appearance of the bud and that capsule growth arrested during budding. Benomyl, which arrests the cells in G2/M, inhibited capsule growth, while sirolimus (rapamycin) addition, which induces G1 arrest, resulted in cells with larger capsule. Furthermore, we have characterized a mutant strain that lacks a putative G1/S cyclin. This mutant showed an increased capacity to enlarge the capsule, both in vivo (using Galleria mellonella as the host model) and in vitro. In the absence of Cln1, there was a significant increase in the production of extracellular vesicles. Proteomic assays suggest that in the cln1 mutant strain, there is an upregulation of the glyoxylate acid cycle. Besides, this cyclin mutant is avirulent at 37°C, which correlates with growth defects at this temperature in rich medium. In addition, the cln1 mutant showed lower intracellular replication rates in murine macrophages. We conclude that cell cycle regulatory elements are involved in the modulation of the expression of the main virulence factor in C. neoformans. IMPORTANCE: Cryptococcus neoformans is a pathogenic fungus that has significant incidence worldwide. Its main virulence factor is a polysaccharide capsule that can increase in size during infection. In this work, we demonstrate that this process occurs in a specific phase of the cell cycle, in particular, in G1. In agreement, mutants that have an abnormal longer G1 phase show larger capsule sizes. We believe that our findings are relevant because they provide a link between capsule growth, cell cycle progression, and virulence in C. neoformans that reveals new aspects about the pathogenicity of this fungus. Moreover, our findings indicate that cell cycle elements could be used as antifungal targets in C. neoformans by affecting both the growth of the cells and the expression of the main virulence factor of this pathogenic yeast.es_ES
dc.description.peerreviewedSíes_ES
dc.description.sponsorshipO.Z. is funded by grants SAF2008-03761 and SAF2011-25140 from the Spanish Ministry for Economics and Competitivity. R.G.-R. is supported by an FPI fellowship (reference BES-2009-015913) from the Spanish Ministry of Science and Innovation. N.T.-C. is supported by an FPI fellowship (reference BES-2012-051837) from the Spanish Ministry for Economics and Competitivity. A.C. is supported by NIH grants HL059842-3, A1033774, A1052733, and AI033142. R.J.B.C. is supported by T32 AI07506 (NIH/NIAID).es_ES
dc.format.number3es_ES
dc.format.pagee00945-14es_ES
dc.format.volume5es_ES
dc.identifier.citationmBio. 2014 Jun 17;5(3):e00945-14.es_ES
dc.identifier.doi10.1128/mBio.00945-14es_ES
dc.identifier.e-issn2150-7511es_ES
dc.identifier.issn2150-7511es_ES
dc.identifier.journalmBioes_ES
dc.identifier.pubmedID24939886es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/9140
dc.language.isoenges_ES
dc.publisherAmerican Society for Microbiology (ASM)es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2008-03761es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2011-25140es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/ BES-2009-015913es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/BES-2012-051837es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/HL059842-3es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/ A1033774es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/A1052733es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/AI033142es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/T32 AI07506es_ES
dc.relation.publisherversionhttps://doi.org/10.1128/mBio.00945-14es_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.repisalud.institucionISCIIIes_ES
dc.rights.accessRightsopen accesses_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshAnimalses_ES
dc.subject.meshBacterial Capsuleses_ES
dc.subject.meshCryptococcosises_ES
dc.subject.meshCryptococcus neoformanses_ES
dc.subject.meshFungal Proteinses_ES
dc.subject.meshHumanses_ES
dc.subject.meshMacrophageses_ES
dc.subject.meshMicees_ES
dc.subject.meshMothses_ES
dc.subject.meshVirulence Factorses_ES
dc.subject.meshCell Cyclees_ES
dc.titleCapsule growth in Cryptococcus neoformans is coordinated with cell cycle progressiones_ES
dc.typejournal articlees_ES
dc.type.hasVersionVoRes_ES
dspace.entity.typePublication
relation.isAuthorOfPublication5a3e7f05-71f7-421c-ae8c-edf6fa6eccf0
relation.isAuthorOfPublicationb524f086-180d-432d-a431-7a63798600f0
relation.isAuthorOfPublication298933e5-bfff-4e88-83ec-e4d2cb6581e1
relation.isAuthorOfPublication.latestForDiscovery5a3e7f05-71f7-421c-ae8c-edf6fa6eccf0
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