- Novel strategies in antifungal lead discovery
Elitra Canada, 225 President Kennedy West, Suite 2550, Montreal, Quebec, H2X 3Y8, Canada
Curr Opin Microbiol 5:466-71. 2002
..Emerging experimental analysis tools, such as fitness profiling and protein microarrays, have greatly enhanced our ability to conduct genome-wide functional studies...
- Large-scale essential gene identification in Candida albicans and applications to antifungal drug discovery
Elitra Canada, Montreal, Quebec, Canada, H2X 3Y8
Mol Microbiol 50:167-81. 2003
..albicans essential gene set, and their respective conditional mutant strains may be directly used as sensitive whole-cell assays for drug screening...
- Essential gene identification and drug target prioritization in Aspergillus fumigatus
Merck Frosst Center of Fungal Genetics, Montreal, Quebec, Canada
PLoS Pathog 3:e24. 2007
..fumigatus essential genes for cognate antifungal inhibitors...
- Mechanism-of-action determination of GMP synthase inhibitors and target validation in Candida albicans and Aspergillus fumigatus
Center of Fungal Genetics, Merck Frosst Canada, Montreal, Quebec H2X 3Y8, Canada
Chem Biol 14:1163-75. 2007
..Importantly, GMP synthase activity is conditionally essential in C. albicans and Aspergillus fumigatus and is required for virulence of both pathogens, thus constituting an unexpected antifungal target...
- Genome-wide fitness test and mechanism-of-action studies of inhibitory compounds in Candida albicans
Center of Fungal Genetics, Merck Frosst Canada Ltd, Montreal, Quebec, Canada
PLoS Pathog 3:e92. 2007
..We also demonstrate how chemically induced haploinsufficiency profiles can be used to identify the mechanism of action of novel antifungal agents, thereby illustrating the potential utility of this approach to antifungal drug discovery...
- PAP inhibitor with in vivo efficacy identified by Candida albicans genetic profiling of natural products
Center of Fungal Genetics, Merck Frosst Canada and Co, 225 President Kennedy West, Suite 2550, Montreal, Quebec H2X 3Y8, Canada
Chem Biol 15:363-74. 2008
..Thus, mechanism-of-action determination of crude fermentation extracts by chemical-genetic profiling brings a powerful strategy to natural-product-based drug discovery...
- Chemical genetic profiling and characterization of small-molecule compounds that affect the biosynthesis of unsaturated fatty acids in Candida albicans
Center of Fungal Genetics, Merck Frosst Canada Ltd, Montreal, Quebec H9H 3L1, Canada
J Biol Chem 284:19754-64. 2009
- Depletion of the cullin Cdc53p induces morphogenetic changes in Candida albicans
Institute for Research in Immunology and Cancer, Universite de Montreal, Montreal, Quebec, Canada
Eukaryot Cell 8:756-67. 2009
..These results indicate that Cdc53p enables C. albicans to adequately respond to environmental signals...
- Transcription factor substitution during the evolution of fungal ribosome regulation
Biotechnology Research Institute, National Research Council, Montreal, QC H4P 2R2, Canada
Mol Cell 29:552-62. 2008
..cerevisiae lineage, this substitution also occurred independently at RP genes, illustrating the extreme adaptability and flexibility of transcriptional regulatory networks...
- Confronting the challenges of natural product-based antifungal discovery
Department of Infectious Disease, Merck Frosst Canada Ltd, Montreal, QC, Canada
Chem Biol 18:148-64. 2011
- High-frequency transposition for determining antibacterial mode of action
Infectious Diseases Division, Merck Frosst Center for Therapeutic Research, Kirkland, Quebec, Canada
Nat Chem Biol 7:720-9. 2011
..Using a panel of antibiotics, we demonstrate the ability to unveil not only an inhibitor's molecular target but also its route of cellular entry, efflux susceptibility and other off-target resistance mechanisms...
- Isolation and structure elucidation of parnafungins, antifungal natural products that inhibit mRNA polyadenylation
Craig A Parish
Natural Products Chemistry, Infectious Diseases, and Process Research, Merck Research Laboratories, Merck and Company, P O Box 2000, Rahway, New Jersey 07065, USA
J Am Chem Soc 130:7060-6. 2008
..The intact isoxazolidinone ring was required for antifungal activity. In addition, the natural products were efficacious in a mouse model of disseminated candidiasis...
- Genomic islands in the pathogenic filamentous fungus Aspergillus fumigatus
Natalie D Fedorova
The J Craig Venter Institute, Rockville, Maryland, United States of America
PLoS Genet 4:e1000046. 2008
..The role of duplication in the origin of lineage-specific genes is further underlined by the discovery of genomic islands that seem to function as designated "gene dumps" and, perhaps, simultaneously, as "gene factories"...