Faculty Opinions recommendation of Identification of Drosophila gene products required for phagocytosis of Candida albicans.

Author(s):  
Sergio Grinstein
PLoS Biology ◽  
2005 ◽  
Vol 4 (1) ◽  
pp. e4 ◽  
Author(s):  
Shannon L Stroschein-Stevenson ◽  
Edan Foley ◽  
Patrick H O'Farrell ◽  
Alexander D Johnson

2012 ◽  
Vol 11 (10) ◽  
pp. 1268-1275 ◽  
Author(s):  
Matthew Z. Anderson ◽  
Joshua A. Baller ◽  
Keely Dulmage ◽  
Lauren Wigen ◽  
Judith Berman

ABSTRACTCandida albicansgrows within a wide range of host niches, and this adaptability enhances its success as a commensal and as a pathogen. The telomere-associatedTLOgene family underwent a recent expansion from one or two copies in other CUG clade members to 14 expressed copies inC. albicans. This correlates with increased virulence and clinical prevalence relative to those of otherCandidaclade species. The 14 expressedTLOgene family members have a conserved Med2 domain at the N terminus, suggesting a role in general transcription. The C-terminal half is more divergent, distinguishing three clades: clade α and clade β have no introns and encode proteins that localize primarily to the nucleus; clade γ sometimes undergoes splicing, and the gene products localize within the mitochondria as well as the nuclei. Additionally,TLOα genes are generally expressed at much higher levels than areTLOγ genes. We propose that expansion of theTLOgene family and the predicted role of Tlo proteins in transcription regulation provideC. albicanswith the ability to adapt rapidly to the broad range of different environmental niches within the human host.


2012 ◽  
Vol 12 (1) ◽  
pp. 101-108 ◽  
Author(s):  
Diane O. Inglis ◽  
Marek S. Skrzypek ◽  
Martha B. Arnaud ◽  
Jonathan Binkley ◽  
Prachi Shah ◽  
...  

ABSTRACTThe opportunistic fungal pathogenCandida albicansis a significant medical threat, especially for immunocompromised patients. Experimental research has focused on specific areas ofC. albicansbiology, with the goal of understanding the multiple factors that contribute to its pathogenic potential. Some of these factors include cell adhesion, invasive or filamentous growth, and the formation of drug-resistant biofilms. The Gene Ontology (GO) (www.geneontology.org) is a standardized vocabulary that theCandidaGenome Database (CGD) (www.candidagenome.org) and other groups use to describe the functions of gene products. To improve the breadth and accuracy of pathogenicity-related gene product descriptions and to facilitate the description of as yet uncharacterized but potentially pathogenicity-related genes inCandidaspecies, CGD undertook a three-part project: first, the addition of terms to the biological process branch of the GO to improve the description of fungus-related processes; second, manual recuration of gene product annotations in CGD to use the improved GO vocabulary; and third, computational ortholog-based transfer of GO annotations from experimentally characterized gene products, using these new terms, to uncharacterized orthologs in otherCandidaspecies. Through genome annotation and analysis, we identified candidate pathogenicity genes in seven non-C. albicans Candidaspecies and in one additionalC. albicansstrain, WO-1. We also defined a set ofC. albicansgenes at the intersection of biofilm formation, filamentous growth, pathogenesis, and phenotypic switching of this opportunistic fungal pathogen, which provides a compelling list of candidates for further experimentation.


2004 ◽  
Vol 48 (9) ◽  
pp. 3425-3435 ◽  
Author(s):  
K. M. Rogers ◽  
C. A. Pierson ◽  
N. T. Culbertson ◽  
C. Mo ◽  
A. M. Sturm ◽  
...  

ABSTRACT Sterol synthesis in fungi is an aerobic process requiring molecular oxygen and, for several cytochrome-mediated reactions, aerobically synthesized heme. Cytochrome b 5 is required for sterol C5-6 desaturation and the encoding gene, CYB5, is nonessential in Saccharomyces cerevisiae. Cyb5p and Ncp1p (cytochrome P-450 reductase) appear to have overlapping functions in this organism, with disruptions of each alone being viable. The cytochrome P-450 reductase phenotype has also been shown to demonstrate increased sensitivity to azole antifungals. Based on this phenotype, the CYB5 gene in the human pathogen Candida albicans was investigated to determine whether the cyb5 genotype was viable and would also demonstrate azole sensitivity. Sequential disruption of the CYB5 alleles by direct transformation resulted in viability, presumably conferred by the presence of a third copy of the CYB5 gene. Subsequent disruption procedures with a pMAL2-CYB5 rescue cassette and a CYB5-URA3 blaster cassette resulted in viable cyb5 strains with no third copy. The C. albicans CYB5 gene is concluded to be nonessential. Thus, the essentiality of this gene and whether we observed two or three alleles was dependent upon the gene disruption protocol. The C. albicans cyb5 strains produced a sterol profile containing low ergosterol levels and sterol intermediates similar to that reported for the S. cerevisiae cyb5. The C. albicans cyb5 shows increased sensitivity to azoles and terbinafine, an inhibitor of squalene epoxidase, and, unexpectedly, increased resistance to morpholines, which inhibit the ERG2 and ERG24 gene products. These results indicate that an inhibitor of Cyb5p would not be lethal but would make the cell significantly more sensitive to azole treatment.


PLoS ONE ◽  
2012 ◽  
Vol 7 (12) ◽  
pp. e51831 ◽  
Author(s):  
Adam Peltan ◽  
Laura Briggs ◽  
Gareth Matthews ◽  
Sean T. Sweeney ◽  
Deborah F. Smith

1999 ◽  
Vol 181 (6) ◽  
pp. 1868-1874 ◽  
Author(s):  
R. Bryce Wilson ◽  
Dana Davis ◽  
Aaron P. Mitchell

ABSTRACT Disruption of newly identified genes in the pathogen Candida albicans is a vital step in determination of gene function. Several gene disruption methods described previously employ long regions of homology flanking a selectable marker. Here, we describe disruption of C. albicans genes with PCR products that have 50 to 60 bp of homology to a genomic sequence on each end of a selectable marker. We used the method to disrupt two known genes,ARG5 and ADE2, and two sequences newly identified through the Candida genome project,HRM101 and ENX3. HRM101 and ENX3are homologous to genes in the conserved RIM101 (previously called RIM1) and PacC pathways ofSaccharomyces cerevisiae and Aspergillus nidulans. We show that three independenthrm101/hrm101 mutants and two independentenx3/enx3 mutants are defective in filamentation on Spider medium. These observations argue that HRM101 andENX3 sequences are indeed portions of genes and that the respective gene products have related functions.


2005 ◽  
Vol 73 (12) ◽  
pp. 7977-7987 ◽  
Author(s):  
Muriel Cornet ◽  
Frédérique Bidard ◽  
Patrick Schwarz ◽  
Grégory Da Costa ◽  
Sylvie Blanchin-Roland ◽  
...  

ABSTRACT Ambient pH signaling involves a cascade of conserved Rim or Pal products in ascomycetous yeasts or filamentous fungi, respectively. Recent evidences in the fungi Aspergillus nidulans, Saccharomyces cerevisiae, Yarrowia lipolytica, and Candida albicans suggested that components of endosomal sorting complexes required for transport (ESCRT) involved in endocytic trafficking were needed for signal transduction along the Rim pathway. In this study, we confirm these findings with C. albicans and show that Vps28p (ESCRT-I) and Vps32p/Snf7p (ESCRT-III) are required for the transcriptional regulation of known targets of the Rim pathway, such as the PHR1 and PHR2 genes encoding cell surface proteins, which are expressed at alkaline and acidic pH, respectively. We additionally show that deletion of these two VPS genes, particularly VPS32, has a more drastic effect than a RIM101 deletion on growth at alkaline pH and that this effect is only partially suppressed by expression of a constitutively active form of Rim101p. Finally, in an in vivo mouse model, both vps null mutants were significantly less virulent than a rim101 mutant, suggesting that VPS28 and VPS32 gene products affect virulence both through Rim-dependent and Rim-independent pathways.


RNA ◽  
2016 ◽  
Vol 23 (2) ◽  
pp. 153-160 ◽  
Author(s):  
Edward M. Kennedy ◽  
Anand V.R. Kornepati ◽  
Hal P. Bogerd ◽  
Bryan R. Cullen

Author(s):  
James M. Slavicek ◽  
Melissa J. Mercer ◽  
Mary Ellen Kelly

Nucleopolyhedroviruses (NPV, family Baculoviridae) produce two morphological forms, a budded virus form and a viral form that is occluded into a paracrystalline protein matrix. This structure is termed a polyhedron and is composed primarily of the protein polyhedrin. Insects are infected by NPVs after ingestion of the polyhedron and release of the occluded virions through dissolution of the polyhedron in the alkaline environment of the insect midgut. Early after infection the budded virus form is produced. It buds through the plasma membrane and then infects other cells. Later in the infection cycle the occluded form of the virus is generated (reviewed by Blissard and Rohrmann, 1990).The processes of polyhedron formation and virion occlusion are likely to involve a number of viral gene products. However, only two genes, the polyhedrin gene and 25K FP gene, have been identified to date that are necessary for the wild type number of polyhedra to be formed and viral particles occluded.


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