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Updated: Aug 19, 2026
Targeted in Situ Mutagenesis of Histone Genes in Budding Yeast
Published on: January 26, 2017
The isolation of FOS-1, a gene encoding a putative two-component histidine kinase from Aspergillus fumigatus
G B Pott1, T K Miller, J A Bartlett
1Department of Cellular and Structural Biology, MycoLogics, Inc., B-111, 4200 E. Ninth Avenue, Denver, Colorado 80262, USA.
Abstract:
In fungi, two-component histidine kinases are involved in response mechanisms to extracellular changes in osmolarity, resistance to dicarboximide fungicides, and cell-wall assembly. In the human opportunistic fungus, Candida albicans, each of the three histidine kinases plays a role in virulence. Here, we identify, for the first time, a gene, FOS-1, from the human pathogenic fungus Aspergillus fumigatus that predicts a protein with homology to two-component histidine kinases. The predicted FOS-1 protein is highly homologous to bacterial and other fungal histidine kinases in several functional domains, but is divergent at the amino- and carboxy-termini. A mutant lacking the FOS-1 locus, DeltaFOS-1, did not exhibit a detectable defect in either hyphal growth or morphology when grown on solid or liquid medium. However, in liquid medium, conidiophore development of the DeltaFOS-1 mutant was delayed. Compared to wild type, the DeltaFOS-1 strain was neither osmotically sensitive nor sensitive or resistant to a number of nondicarboximide antifungal drugs, but was highly resistant to dicarboximide fungicides and resistant to novozym 234, suggesting that FOS-1p may play a role in the regulation of cell-wall assembly.
Insights
Researchers identified the FOS-1 gene in Aspergillus fumigatus, revealing its role in fungal development and resistance to specific fungicides. This discovery offers new insights into pathogenic fungi and potential drug targets.
Area of Science:
- Mycology
- Molecular Biology
- Biochemistry
Background:
- Two-component histidine kinases regulate fungal responses to environmental changes.
- In Candida albicans, histidine kinases are crucial for virulence.
- Aspergillus fumigatus is a significant human opportunistic pathogen.
Purpose of the Study:
- To identify and characterize novel two-component histidine kinase genes in Aspergillus fumigatus.
- To investigate the function of the FOS-1 gene in Aspergillus fumigatus development and stress response.
Main Methods:
- Gene identification and sequence homology analysis.
- Construction and phenotypic analysis of a FOS-1 deletion mutant (DeltaFOS-1).
- Assessment of osmotic sensitivity, drug resistance, and morphological changes.
Main Results:
- The FOS-1 gene encodes a protein with homology to known histidine kinases.
- The DeltaFOS-1 mutant showed delayed conidiophore development in liquid medium.
- The mutant exhibited high resistance to dicarboximide fungicides and Novozym 234, but no altered osmotic or general antifungal drug sensitivity.
Conclusions:
- FOS-1p is a novel two-component histidine kinase in Aspergillus fumigatus.
- FOS-1 plays a role in regulating conidiophore development and cell-wall assembly.
- FOS-1 is implicated in resistance to dicarboximide fungicides, suggesting potential therapeutic targets.
