Recent sequencing and assembly of the genome for the fungal pathogen Candida albicans used simple automated procedures for the identification of putative genes. We have reviewed the entire assembly, both by hand and with additional bioinformatic resources, to accurately map and describe 6,354 genes and to identify 246 genes whose original database entries contained sequencing errors (or possibly mutations) that affect their reading frame. Comparison with other fungal genomes permitted the identification of numerous fungus-specific genes that might be targeted for antifungal therapy. We also observed that, compared to other fungi, the protein-coding sequences in the C. albicans genome are especially rich in short sequence repeats. Finally, our improved annotation permitted a detailed analysis of several multigene families, and comparative genomic studies showed that C. albicans has a far greater catabolic range, encoding respiratory Complex 1, several novel oxidoreductases and ketone body degrading enzymes, malonyl-CoA and enoyl-CoA carriers, several novel amino acid degrading enzymes, a variety of secreted catabolic lipases and proteases, and numerous transporters to assimilate the resulting nutrients. The results of these efforts will ensure that the Candida research community has uniform and comprehensive genomic information for medical research as well as for future diagnostic and therapeutic applications.
Superoxide dismutases (SOD) convert superoxide radicals into less damaging hydrogen peroxide. The opportunistic human pathogen Candida albicans is known to express CuZnSOD (SOD1) and MnSOD (SOD3) in the cytosol and MnSOD (SOD2) in the mitochondria. We identified three additional CuZn-containing superoxide dismutases, SOD4, SOD5, and SOD6, within the sequence of the C. albicans genome. The transcription of SOD5 was up-regulated during the yeast to hyphal transition of C. albicans, and SOD5 was induced when C. albicans cells were challenged with osmotic or with oxidative stresses. SOD5 transcription was also increased when cells were grown on nonfermentable substrates as the only carbon source. The Rim101p transcription factor was required for all inductions observed, whereas the Efg1p transcription factor was specifically needed for serum-modulated expression. Deletion of SOD5 produced a viable mutant strain that showed sensitivity to hydrogen peroxide when cells were grown in nutrient-limited conditions. Sod5p was found to be necessary for the virulence of C. albicans in a mouse model of infection. However, the sod5 mutant strain showed the same resistance to macrophage attack as its parental strain, suggesting that the loss of virulence in not due to an increased sensitivity to macrophage attack. INTRODUCTIONAerobic eukaryotic pathogens can encounter superoxide radicals (O 2 Ϫ ) generated from several sources. These sources can be internal or external. An important internal source is the mitochondrial respiratory chain (Boveris, 1978;Casteilla et al., 2001;Lenaz, 2001), and thus the rate of respiration can have a significant impact on reactive oxygen species (ROS) production. A key external source of ROS encountered by pathogens is from phagocytes. The superoxide radical is the first intermediate in the oxidative burst generated in the phagosome, and this burst is thought to be involved in pathogen killing (Reeves et al., 2002). The superoxide radicals are known to inactivate [4Fe-4S] cluster-containing enzymes by oxidizing one iron and releasing it from the cluster (Liochev and Fridovich, 1994;Fridovich, 1995). Free iron can react with hydrogen peroxide to generate toxic hydroxyl radicals (OH Ϫ ) by Fenton chemistry (Fridovich, 1978;Meneghini, 1997). The hydroxyl and superoxide radicals react with cellular components, resulting in oxidation of proteins and nucleic acids as well as lipid peroxidation. These effects can lead to inactivation of enzymes, to disruption of membranes, to mutations, and ultimately to cell death Gutteridge, 1990, 1999).To reduce the harmful effects of superoxide radicals, cells express detoxifying enzymes. Superoxide dismutase (SOD) is an antioxidant enzyme involved in elimination of superoxide anions; it catalyzes the reaction: O 2 Ϫ ϩ O 2 Ϫ ϩ 2H ϩ 3 H 2 O 2 ϩ O 2 . Normally, H 2 O 2 is still toxic to the cell; therefore, another enzyme, catalase, converts it to water. Superoxide dismutases can be classified according to metal cofactor(s) bound to them: there are iron (FeSOD), mangan...
Although the cellular process of galactose induction of the Leloir pathway is conserved between the two organisms, the regulatory circuits achieving the cellular process are completely distinct.
Background: The 10.9× genomic sequence of Candida albicans, the most important human fungal pathogen, was published in 2004. Assembly 19 consisted of 412 supercontigs, of which 266 were a haploid set, since this fungus is diploid and contains an extensive degree of heterozygosity but lacks a complete sexual cycle. However, sequences of specific chromosomes were not determined.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.