A multi-host approach for the systematic analysis of virulence factors in Cryptococcus neoformans.
A multi-host approach was followed to screen a library of 1201 signature-tagged deletion strains of Cryptococcus neoformans mutants to identify previously unknown virulence factors. The primary screen was performed using a Caenorhabditis elegans-C. neoformans infection assay. The hits among these st...
| Publicado en: | Journal of Infectious Diseases Vol. 211; no. 2; pp. 298 - 306 |
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| Autores principales: | , , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
Oxford University Press / USA
Jan2015
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=103874106&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 103874106 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00221899 1YU jtl: Journal of Infectious Diseases issn: 00221899 maglogo: N pubinfo: dt: Jan2015 vid: 211 iid: 2 pid: 622 pub: Oxford University Press / USA artinfo: ui: 103874106 103874106 NLM25114160 2012869263 10.1093/infdis/jiu441 NLM25114160 PMC4342695 103874106 ppf: 298 ppct: 8 formats: tig: atl: A multi-host approach for the systematic analysis of virulence factors in Cryptococcus neoformans. aug: au: Desalermos, Athanasios Tan, Xiaojiang Rajamuthiah, Rajmohan Arvanitis, Marios Wang, Yan Li, Dedong Kourkoumpetis, Themistoklis K Fuchs, Beth Burgwyn Mylonakis, Eleftherios affil: Division of Infectious diseases, Warren Alpert Medical School of Brown University, Providence, Rhode Island. sug: subj: Cryptococcus Moths Microbiology Nematodes Microbiology Toxins Analysis Animal Studies Cryptococcosis Microbiology Cryptococcosis Pathology Female Genetic Screening Mice Models, Biological Mutation Toxins Female ab: A multi-host approach was followed to screen a library of 1201 signature-tagged deletion strains of Cryptococcus neoformans mutants to identify previously unknown virulence factors. The primary screen was performed using a Caenorhabditis elegans-C. neoformans infection assay. The hits among these strains were reconfirmed as less virulent than the wild type in the insect Galleria mellonella-C. neoformans infection assay. After this 2-stage screen, and to prioritize hits, we performed serial evaluations of the selected strains, using the C. elegans model. All hit strains identified through these studies were validated in a murine model of systemic cryptococcosis. Twelve strains were identified through a stepwise screening assay. Among them, 4 (CSN1201, SRE1, RDI1, and YLR243W) were previously discovered, providing proof of principle for this approach, while the role of the remaining 8 genes (CKS101, CNC5600, YOL003C, CND1850, MLH3, HAP502, MSL5, and CNA2580) were not previously described in cryptococcal virulence. The multi-host approach is an efficient method of studying the pathogenesis of C. neoformans. We used diverse model hosts, C. elegans, G. mellonella, and mice, with physiological differences and identified 12 genes associated with mammalian infection. Our approach may be suitable for large pathogenesis screens. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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