study of the yeast infection candida

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Candida comes from the Latin meaning 'clearish white', the meaning of this word is yeast infection ( Candida Albicans is a diploid fungus (cited L. Giblin et al., 2001) it is normally found on the skin and mucous membranes in the mouth, rectum, or vagina. It is widely known to spread a type of yeast infection that starts spreading through the digestive system and spreads its way to other parts of the body, in severe cases it gets attached to the intestinal wall and permanently resides in the internal organs. This fungus causes numerous health problems if not treated at the right time (

Various researches were done on this particular species in which it was found that Candida Albicans is a dimorphic fungus which made them commensal, which means it lives with the other flora in the gut without causing any particular harm. It thrives in oxygen free environment so it is anaerobic in nature. It can produce hyphae and pseudohyphae so it is polymorphic(cited L.A. Walker et al., 2009). It has some similar function with food yeasts, but they do not have the same ability as Candida to hold on and colonize the mucous membranes. It is commonly found in the in the soil environmen(

Figure 1: candida albicans (Kunkel ,2004)

A interesting fact of Candida Albicans is that it can grow in different ways , some by reproducing through budding mechanism forming an ellipsoid bud and in hyphal form which gets fragmented periodically giving rise to new mycelia or another yeast forms. (Molero, 1998) C. albicans has a diploid genome and has no clear defined sexual cycle (cited Andre Nantel,2006). Consequently, classical genetic approaches have been of limited value for studying this organism. C.albicans is a diploid organism which has 8 sets of chromosome pairs and its genome size is about 16Mb (ICE,2004) The genomic sequence of C. albicans strain SC5314 was published in 2004 as an assembly comprising 266 contiguous segments across a haploid reference genome. The whole-genome shotgun sequencing to 10.9X coverage and the construction of Assembly 6 with PHRAP( The recent availability of genome sequences for related pathogenic and nonpathogenic fungi has enabled the use of comparative genomics approaches to refine the open reading frame (ORF) catalog and gene annotation, as well as to examine gene families that have expanded in the pathogenic fungi (cited Martha B. et al.,2009).The genome of Candida albicans have 2600 repeat-containing ORFs. There are three or ten times respectively more than yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe (Braun BR et al,2005).

To understand more in detail, a further detailed study on the importance , gene structure and genomic aspect of this organism, how were the sequencing done and various recent advances made on this particular organism were discussed as follow.

Life cycle of Candida albicans:

Figure 2: Candida albicans dimorphism.

Candida albicans life cycle is dimorphic. That means that this life cycle includes two stages - yeast stage and hyphae stage. Here five steps described for its cycle (A) A spore formed by budding, as in yeast is known as a Blastospores and they are unicellular forms of the fungus that divide by budding. (B) In the presence of some environmental factors, cylindrical outgrowth is initiated on the surface of a blastospore forming a germ tube. (C) Germ tubes grow and septa are laid down behind the extending apical tip to form a hypha. (D) Hyphal branches or secondary branches are produced just behind newly laid-down septa, constituting a micelium.(E) Secondary blastospores become separated from the filament. The main factors that good turn filamentation are: temperature 35°C, pH 7.0, an inoculum of 1 Ã- 106 blastospores/ml, and the presence of different compounds, such as N-acetylglucosamine, proline or serum (molero,1998).

Sequencing of the Candida albicans genome:

Candida albicans is the best studied of the human fungal and it is used as a model organism for the study of other pathogenic fungi.(Arnaud et al,2005).After several years investigation of pathogenic yeast C.albicans have had internet access to partial genomic sequence information (Odds et al,2004).There are two different researchers for studied sequencing of c.albicans. One is from University of Minnesota with the early interest of Stewart Scherer and Paul T. Magee (Scherer et al,1990) and another is Stanford Genome Technology Center, headed by Ron Davis. Davis and his team were succeeded to finished diploid sequence. The main evidence of the C.albicans genome sequence has eight chromosomes.Haploid genome size is 14,851kb which containing 6,419 ORFs(Open Reading Frames).longer than 100 codons in which 20% are un known.CUG codon is translated abnormally by C.albicans as serine rather than leucine but it happened very rare in approximately two-third of ORFs(Odds et al,2004).Whole-genome shotgun sequencing was carried out at Stanford University where the sequences were assembled into 412 contigs. C. albicans is a basically diploid and sequence analysis is complicated due to repeated sequences and to sequence polymorphism between homologous chromosomes. Chromosome 7 is assigned 16 of the contigs which length is from7309 to 267,590 bp and determined sequences of 16 regions. These regions included four gaps, amisassembled sequence, and two major repeat sequences (MRS) which length is 16 kb( Chibana et al,2005).The C. albicans genome sequence to the public domain at various stages of conclusion has already increased speed research in the biology and disease processes of this important pathogen. The availability of a diploid genome sequence will now take these studies to a new level. The genome sequence now provides an invaluable platform for the genomic screens that are so vital in the absence of genetic screens(Odds et al,2004).

Strains of Candida albicans :

c.albicans has various types of strains which are used in differ significantly in virulence as measured by depth of fungal invasion into corneas and clinical evaluation of infection. Further characterization of the intrinsic genetic differences between such strains may help identify factors responsible for fungal virulence (O'Day HYPERLINK ""O'Day DM"[Author]"et alHYPERLINK ""O'Day DM"[Author]",2000)HYPERLINK ""O'Day DM"[Author]"  Typing of C. albicans strains is mainly based on genotypic methods(Sandt et al,2003). There are many strains of c.albicans like SC5314 ,CAF2-1, CAI4, CAI8, P37005, Red3/6, RM1000, BWP17, SN87, SN95, SN152, WO-1, WUM5A.SC5314 which genotype is wild type and it is used in the systematic sequencing project. The original strain background from which most of the common laboratory strains are derived. This strain is virulent in a mouse model of systemic infection and is frequently used as a wild-type control.( Gillum et al,1984). CAF2-1 which genotype URA3/ura3::imm434 IRO1/iro1:: imm434 and URA3 heterozygous strain derived from the SC5314 strain. The 3-prime end of one copy of the IRO1 gene that resides adjacent to URA3 was inadvertently deleted during the construction of this strain. This strain is virulent in a mouse model of systemic infection and is frequently used as a wild-type control. CAI8 which Genotype is  ura3::imm434/ura3:: imm 434  iro1/iro1/::imm434 ade2::hisG/ade2::hisG and it is Isogenic to the SC5314 strain. Derived from the CAF2-1 strain by deletion of URA3 and both copies of ADE2 using the URA-blaster method(Fonzi et al,1993).CAI4 which Genotype is ura3:: imm434/ura3:: imm 434 iro1/iro1::imm434 and it is Isogenic to the SC5314 strain. Uridine auxotroph constructed by deletion of the second copy of URA3. The second copy of IRO1 was inadvertently deleted upon strain construction. This strain is a virulent in a mouse model of systemic infection unless complemented with URA3(Garcia et al,2001). SN87 and SN95 which is used Isogenic to the SC5314 strain. Histidine and leucine or arginine respectively auxotroph derived from the RM1000#2 strain by deletion of the LEU2 gene and ARG4 gene respectively.( Noble et al ,2005)

Candida albicans tRNA genes:

C.albicans strain SC5314 contains 6244 annotated entries analogous to 130 tRNA genes and 5917 protein-coding genes. For these, it provides hesitant functional assignments along with numerous pre-run analyses that can assist the researcher in the evaluation of gene function for the purpose of specific or large-scale analysis (d'Enfert et al,2005).

Fig. 3 tRNA sequences from C. albicans nucleus

Transfer RNA play important roles in regulating gene expression. By using tRNAscan-SE it have identified that C. albicans have total of 132 tRNA genes. These tRNA genes represent 43 unique tRNA gene species decoding all of the 20 amino acids, from the mitochondrial genome of C. albicans, a total of 162 tRNA genes were used in study. Since the "universal" leucine codon CTG specially encodes for serine in C. albicans, this non-standard translational event may add some special features to the tRNA genes. Phylogenetic relationships of tRNA genes from the nuclear and mitochondrial genomes were compared to demonstrate some recent gene duplications and interorganellar gene transfer. The correlation of codon usage with copy numbers of the tRNA gene (

Candida albicans Ribosomal Genes:

Ribosomal RNA sequences have been shown to be a target of choice for the inter and intraspecies identification and classification of a number of microorganisms. The sequence of the 25S rRNA of C.albicans, the most common pathogenic yeast. The total length of the 25S rRNA is 3361 bp or 3363 bp. The insertion responsible for this difference (Mercur et al,1993). 25S rRNA polyadenylation is part of the biological repertoire of C. albicans and its transient upregulation just prior to hyphal development raises the possibility of a regulatory role in this transition( Fleischmann et al,2001). 26S rRNA gene of C. albicans is used Folding of the group I intron ribozyme and indicate that group I intron of Tetrahymena, multiple folding pathways exist for is also play a role in the multiple folding pathways leading to the catalytically active form may differ between folding of these two group I introns.( Zhang et al,2010)

Candida albicans mitochondrial genome:

The size of mitochondrial DNA (mtDNA) of the dimorphic fungus C.albicans is 41 kilobase pairs.(Wills et al,1985)

FIG. 3. Circular restriction map of C. albicans mtDNA.

Above figure is about EcoRI (E) and PvuII (P) restriction sites which are indicated within the circles. KpnI restriction sites (K) determined from the cloned fragments are indicated on the periphery. The heavy arcs indicate the approximate position of the inverted duplication (ANDREW et al ,1989) Human immunodeficiency virus-positive patients have 45 strains in which total 2,553 nucleotides,62 polymorphic nucleotide sites and seven indels defined nine distinct mtDNA haplotypes of mitochondrial DNA (mtDNA) in C. Albicans with seven Seven regions.mtDNA haplotypes, multilocus nuclear genotypes were almost similar to comparison of nuclear DNA genotypes and concleded taht clonal proliferation of the mitochondrial genome was escorted by clonal proliferation of the nuclear genome(Anderson et al,2001).use of mitochondrial haplotypes in phylogenetic studies should be approached with care and it is also used to further evidence for recombination and genetic exchange in the biology of C. albicans( MD et al,2008). Molecular recombination and transcription are proposed mechanisms to initiate mitochondrial DNA (mtDNA) replication in yeast. The topological evidence for recombination-driven mtDNA replication initiation and introduce C. albicans as a suitable model organism to study wild-type mtDNA maintenance in yeast( Gerhold et al,2010)