- a diploid fungus
- seems to have homologs of all the elements of a functional pheromone repsonse pathway of S. cerevisiae but lacks many homologs of genes for meiosis.
Candida albicans is one of the most commonly encountered human pathogens, causing a wide variety of infections ranging from mucosal infections in generally healthy persons to life-threatening systemic infections in individuals with impaired immunity. Oral and esophogeal Candida infections are frequently seen in AIDS patients. Few classes of drugs are effective against these fungal infections, and all of them have limitations with regard to efficacy and side-effects.
C. albicans is an opportunistic pathogen that can cause disease in patients immunocompromised as a result of HIV infection, organ transplantation, and cancer chemotherapy (5). It is also a morphologically complex organism capable of proliferating either as a budding yeast or by the formation of pseudohyphae or filamentous hyphae.
Genetic manipulation of the MTL locus resulted in the demonstration that C. albicans strains can mate to produce triploid or tetraploid progeny at very low frequency either in culture or in experimental animals (3, 4). It thus appears that Candida can undergo cell fusion, depending on mating type. However, completion of a sexual cycle, i.e., meiosis and sporulation, remains to be demonstrated.
Given the evolutionary proximity between C. albicans and S. cerevisiae (6) and the differences in their virulence and habitat, genomic comparisons between these fungi are likely to illuminate aspects of the unique cell biology of both organisms.
C. albicans homologues for STE20, STE11, STE7, and FUS3 genes in the MAP kinase cascade have been identified, as well as homologues of the pheromone receptor genes STE2 and STE3. Genes involved in pheromone processing in S. cerevisiae such as STE14, AXL1, STE23, RAM1, RAM2, STE24, RCE1, KEX2, KEX1, and STE13 (16) have homologues in the Candida genome, although there is no independent evidence that C. albicans can produce or respond to pheromones.
C. albicans may have preserved the ability to produce and respond to mating pheromones. Although extensive BLAST analysis failed to identify any mating-factor homologues, computer programs that take into account pheromone gene structure have provided us with several candidates for pheromone genes (unpublished results).
Virulence of cst20/ste20 and cph1/ste12 disruption mutants is attenuated in the mouse model of systemic candidasis (21, 22), thereby establishing a potential link between pheromone signaling, filamentous growth, and virulence, as found in the pathogenic fungi Cryptococcus neoformans and Ustilago maydis.
The complexity and cross talk between nutritional and meiotic pathways suggest that, although similar genes may be present in both organisms, their participation in these pathways may have different biological consequences. For example, SNF1 is essential for the viability of C. albicans (28) but is not essential in S. cerevisiae, where it coordinates glucose and acetate regulation of the early and late meiotic program (29). Another homologue found in C. albicans, MCK1, encodes a serine-threonine-tyrosine kinase, which functions as a positive regulator of meiotic gene expression in S. cerevisiae and is essential for ascus maturation; it governs centromere behavior in mitosis.
The absence of IME1 suggests that the switch machinery used in S. cerevisiae to effect commitment to the meiotic pathway is missing. It remains possible that a functional analogue of IME1 is present in C. albicans.
- C. albicans has a MTL and mating between strains carrying different types of MTL.
- C. albicans contains an MTL that encodes proteins similar to a1, alpha1 and alpha2.
- in Candida albicans the ‘universal’ leucine codon CUG is decoded as serine rather than leucine
- The results reveal that these two diverged yeasts show a surprising similarity in their mating processes.
- Pheromone processing genes and (S cerevisiae homologs)
- KEX2 (KEX2)
- HST6 (STE6)
- ALS1 (SAG1)
- INT1 (none)
- Chen J, Chen J, Lane S, and Liu H. A conserved mitogen-activated protein kinase pathway is required for mating in Candida albicans. Mol Microbiol. 2002 Dec;46(5):1335-44.
- O'Sullivan JM, Mihr MJ, Santos MA, and Tuite MF. The Candida albicans gene encoding the cytoplasmic leucyl-tRNA synthetase: implications for the evolution of CUG codon reassignment. Gene. 2001 Sep 5;275(1):133-40.
- Magee BB, Legrand M, Alarco AM, Raymond M, and Magee PT. Many of the genes required for mating in Saccharomyces cerevisiae are also required for mating in Candida albicans. Mol Microbiol. 2002 Dec;46(5):1345-51.
- Tzung KW, Williams RM, Scherer S, Federspiel N, Jones T, Hansen N, Bivolarevic V, Huizar L, Komp C, Surzycki R, Tamse R, Davis RW, and Agabian N. Genomic evidence for a complete sexual cycle in Candida albicans. Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3249-53. DOI:10.1073/pnas.061628798 |