The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Large‐scale essential gene identification in Candida albicans and applications to antifungal drug discovery
Abstract
Summary: Candida albicans is the primary fungal pathogen of humans. Despite the need for novel drugs to combat fungal infections [Sobel, J.D. (2000) Clin Infectious Dis 30: 652], antifungal drug discovery is currently limited by both the availability of suitable drug targets and assays to screen corresponding targets. A functional genomics approach based on the diploid C. albicans genome sequence, termed GRACE TM (gene replacement and conditional expression), was used to assess gene essentiality through a combination of gene replacement and conditional gene expression. In a systematic application of this approach, we identify 567 essential genes in C. albicans. Interestingly, evaluating the conditional phenotype of all identifiable C. albicans homologues of the Saccharomyces cerevisiae essential gene set [Giaever, G., Chu, A.M., Ni, L., Connelly, C., Riles, L., Veronneau, S., et al. (2002) Nature 418: 387–391] by GRACE revealed only 61% to be essential in C. albicans, emphasizing the importance of performing such studies directly within the pathogen. Construction of this conditional mutant strain collection facilitates large‐scale examination of terminal phenotypes of essential genes. This information enables preferred drug targets to be selected from the C. albicans essential gene set by phenotypic information derived both in vitro, such as cidal versus static terminal phenotypes, as well as in vivo through virulence studies using conditional strains in an animal model of infection. In addition, the combination of phenotypic and bioinformatic analyses further improves drug target selection from the C. albicans essential gene set, and their respective conditional mutant strains may be directly used as sensitive whole‐cell assays for drug screening.
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Zhou, N., Jiang, Y., Bergquist, T. R., Lee, A. J., Kacsoh, B. Z., Crocker, A. W., Lewis, K. A., Georghiou, G., Nguyen, H. N., Hamid, M. N., et al. (2019) · Genome Biology · doi:10.1186/s13059-019-1835-8 · Cited by 452
Metadata
- Authors
- Roemer, T., Jiang, B., Davison, J., Ketela, T., Veillette, K., Breton, A., Tandia, F., Linteau, A., Sillaots, S., Marta, C., Martel, N., Veronneau, S., Lemieux, S., Kauffman, S., Becker, J., Storms, R., Boone, C., & Bussey, H.
- Venue
- Molecular Microbiology
- Publisher
- Wiley
- Published
- 2003-08-27
- Volume
- 50
- Issue
- 1
- Pages
- 167-181
- ISSN
- 0950-382X (ISSN-L)
- 1365-2958
- OpenAlex
- W1503938960
- Cited by
- 512
- References
- 47
- FWCI
- 3.86
- Type
- journal article
- Language
- en
- Open access
- closed
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- Roemer, T., Jiang, B., Davison, J., Ketela, T., Veillette, K., Breton, A., Tandia, F., Linteau, A., Sillaots, S., Marta, C., Martel, N., Veronneau, S., Lemieux, S., Kauffman, S., Becker, J., Storms, R., Boone, C., & Bussey, H. (2003). Large‐scale essential gene identification in Candida albicans and applications to antifungal drug discovery. Molecular Microbiology. https://doi.org/10.1046/j.1365-2958.2003.03697.x
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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