Candida albicans
411673
225099116
2008-07-11T21:39:34Z
128.195.221.74
/* Dimorphism */
{{Taxobox
| name = ''Candida albicans''
| image = Candida albicans.jpg
| image_width = 250px
| regnum = [[Fungi]]
| division = [[Ascomycota]]
| phylum = [[Ascomycota]]
| subphylum = [[Saccharomycotina]]
| classis = [[Saccharomycetes]]
| ordo = [[Saccharomycetales]]
| familia = [[Saccharomycetaceae]]
| genus = ''[[Candida (genus)|Candida]]''
| species = '''''C. albicans'''''
| binomial = ''Candida albicans''
| binomial_authority = (C.P. Robin)<br />[[Christine Marie Berkhout|Berkhout]] 1923
| synonyms = ''Candida stellatoidea''<ref>[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=5476&lvl=3&lin=f&keep=1&srchmode=1&unlock Candida albicans at NCBI Taxonomy browser], url accessed 2006-12-26</ref>
''Oidium albicans''<ref>"Factors Affecting the Morphology of Candida Albicans" Dan Otho McClary ''Annals of the Missouri Botanical Garden'', Vol. '''39''', No. 2 (May, 1952), pp. 137-164. doi:10.2307/2394509</ref>
}}
'''''Candida albicans''''' is a [[diploid]] [[fungus]] (a form of [[yeast]]), which is capable of mating but not of meiosis, and a causal agent of [[Opportunistic infection|opportunistic]] [[Wiktionary:oral|oral]] and [[genital]] infections in humans.<ref name=Sherris>{{cite book | author = Ryan KJ; Ray CG (editors) | title = Sherris Medical Microbiology | edition = 4th ed. | publisher = McGraw Hill | year = 2004 | id = ISBN 0-8385-8529-9 }}</ref><ref name=Enfert>{{cite book | author = dEnfert C; Hube B (editors) | title = Candida: Comparative and Functional Genomics | publisher = Caister Academic Press | year = 2007 | id = ISBN 9781904455134 }}</ref> Systemic fungal infections ([[fungemia]]s) have emerged as important causes of [[morbidity]] and [[death|mortality]] in [[Immunodeficiency|immunocompromise]]d patients (e.g., [[AIDS]], cancer [[chemotherapy]], organ or [[bone marrow]] transplantation). In addition, hospital-related infections in patients not previously considered at risk (e.g. patients in an intensive care unit) have become a cause of major health concern.
''C. albicans'' is among the [[gut flora]], the many organisms which live in the human mouth and [[gastrointestinal tract]]. Under normal circumstances, ''C. albicans'' lives in 80% of the human population with no harmful effects, although overgrowth results in [[candidiasis]]. Candidiasis is often observed in [[Immunodeficiency|immunocompromise]]d individuals such as [[HIV]]-positive patients. Candidiasis also may occur in the [[blood]] and in the [[genital]] tract. Candidiasis, also known as "thrush", is a common condition which is usually easily cured in people who are not immunocompromised. To infect host tissue, the usual [[unicellular organism|unicellular]] [[yeast]]-like form of ''Candida albicans'' reacts to environmental cues and switches into an invasive, multicellular filamentous forms.<ref name=Sherris />
== Genome ==
One of the most interesting features of the ''C. albicans'' genome is the occurrence of numeric and structural [[chromosome|chromosomal]] rearrangements as means of generating genetic diversity, named chromosome length polymorphisms (contraction/expansion of repeats), reciprocal [[Chromosomal translocation|translocations]], chromosome [[genetic deletion|deletions]] and [[trisomy]] of individual chromosomes. These [[karyotype|karyotypic]] alterations lead to changes in the phenotype, which is an [[adaptation]] strategy of this fungus. These mechanisms will be better understood with the complete analysis of the ''C. albicans'' genome.
The ''Candida albicans'' genome for strain SC5314 was [[DNA sequencing|sequenced]] at the [[Stanford DNA Sequencing and Technology Center]].<ref>{{cite journal |author=Jones T, Federspiel N, Chibana H, Dungan J, Kalman S, Magee B, Newport G, Thorstenson Y, Agabian N, Magee P, Davis R, Scherer S |title=The diploid genome sequence of Candida albicans |journal=Proc Natl Acad Sci U S A |volume=101 |issue=19 |pages=7329–34 |year=2004 |pmid=15123810 |doi=10.1073/pnas.0401648101}}</ref><ref>{{cite journal |author=Braun B, van Het Hoog M, d'Enfert C, Martchenko M, Dungan J, Kuo A, Inglis D, Uhl M, Hogues H, Berriman M, Lorenz M, Levitin A, Oberholzer U, Bachewich C, Harcus D, Marcil A, Dignard D, Iouk T, Zito R, Frangeul L, Tekaia F, Rutherford K, Wang E, Munro C, Bates S, Gow N, Hoyer L, K�hler G, Morschh�user J, Newport G, Znaidi S, Raymond M, Turcotte B, Sherlock G, Costanzo M, Ihmels J, Berman J, Sanglard D, Agabian N, Mitchell A, Johnson A, Whiteway M, Nantel A |title=A human-curated annotation of the Candida albicans genome |journal=PLoS Genet |volume=1 |issue=1 |pages=36–57 |year=2005 |pmid=16103911 |doi=10.1371/journal.pgen.0010001}}</ref> The genome of the WO1 strain was sequenced by the [[Broad Institute|Broad Institute of MIT and Harvard]].<ref>[http://www.broad.mit.edu/annotation/genome/candida_albicans/ Candida albicans Database - Broad Institute<!-- Bot generated title -->]</ref>
The sequencing of the ''C. albicans'' genome and subsequently of the genomes of several other medically relevant ''Candida'' species has profoundly and irreversibly changed the way ''Candida'' species are now investigated and understood.<ref name=Enfert>{{cite book | author = dEnfert C; Hube B (editors) | title = Candida: Comparative and Functional Genomics | publisher = Caister Academic Press | year = 2007 | id = ISBN 978-1-904455-13-4 }}</ref> The ''C. albicans'' genome sequencing effort was launched in October 1996. Successive releases of the sequencing data and genome assemblies have marked the last 10 years, culminating with the release of the diploid assembly 19 which provided a haploid version of the genome along with data on allelic regions in the genome.<ref name=Enfert>{{cite book | author = dEnfert C; Hube B (editors) | title = Candida: Comparative and Functional Genomics | publisher = Caister Academic Press | year = 2007 | id = ISBN 978-1-904455-13-4 }}</ref> A refined assembly 20 with the eight assembled ''C. albicans'' chromosomes was released in the summer of 2006. Importantly, the availability of sequencing data prior to the completion of the genome sequence has made it possible to start ''C. albicans'' post-genomics early on. In this regard, genome databases have been made available to the research community providing different forms of genome annotation. These have been merged in a community-based annotation hosted by the ''Candida'' Genome Database. The availability of the genome sequence has paved the way for the implementation of post-genomic approaches to the study of ''C. albicans'': macroarrays and then microarrays have been developed and used to study the ''C. albicans'' transcriptome; proteomics has also been developed and complements transcriptional analyses; furthermore, systematic approaches are becoming available to study the contribution of each ''C. albicans'' gene in different contexts. Other ''Candida'' genome sequences have been, or are being, determined: ''C. glabrata'', ''C. dubliniensis'', ''C. parapsilosis'', ''C. guilliermondii'', ''C. lusitaniae'', and ''C. tropicalis''. These species will soon enter the post-genomic era as well and provide interesting comparative data. The genome sequences obtained for the different ''Candida'' species along with those of non-pathogenic hemiascomycetes provide a wealth of knowledge on the evolutionary processes which have shaped the hemiascomycete group as well as those which may have contributed to the success of different ''Candida'' species as pathogens.<ref name=Enfert>{{cite book | author = dEnfert C; Hube B (editors) | title = Candida: Comparative and Functional Genomics | publisher = Caister Academic Press | year = 2007 | id = ISBN 978-1-904455-13-4 }}</ref>
The genome of ''C. albicans'' is highly dynamic and this variability has been used advantageously for molecular epidemiological studies of ''C. albicans'' and population studies in this species. A remarkable discovery which has arisen from the genome sequence is the presence of a parasexual cycle in ''C. albicans''. This parasexual cycle is under the control of mating-type loci and switching between white and opaque phenotypes. Investigating the role which the mating process plays in the dynamics of the ''C. albicans'' population or in other aspects of ''C. albicans'' biology and pathogenicity will undoubtedly represent an important focus for future research.<ref name=Enfert>{{cite book | author = dEnfert C; Hube B (editors) | title = Candida: Comparative and Functional Genomics | publisher = Caister Academic Press | year = 2007 | id = ISBN 9781904455134 }}</ref>
== Dimorphism ==
{{Unreferencedsection|date=January 2007}}
[[Image:Whiteopaquecandida.jpg|Round white-phase and elongated opaque-phase Candida albicans cells.|thumb]]
[[Image:Whiteopaqueregulation.jpg|thumb|Model of the genetic network regulating the white-opaque switch. White and gold boxes represent genes enriched in the white and opaque states, respectively. Blue lines represent relationships based on genetic epistasis. Red lines represent Wor1 control of each gene, based on Wor1 enrichment in chromatin immunoprecipitation experiments. Activation (arrowhead) and repression (bar) are inferred based on white- and opaque-state expression of each gene.]]
In a process which superficially resembles [[Sexual dimorphism|dimorphism]], ''C. albicans'' undergoes a process called [[phenotypic switching]], in which different cellular morphologies are generated spontaneously. One of the classically studied strains which undergoes phenotypic switching is WO-1<ref>{{cite journal |author=Rikkerrink E, Magee B, Magee P |title=Opque-white phenotype transition: a programmed morphological transition in Candida albicans |journal=J. Bact. |volume=170 |issue=2 |pages=895-899 |year=1988}}</ref>, which consists of two phases - one which grows as smooth white colonies and one which is rod-like and grows as flat gray colonies. The other strain known to undergo switching is 3153A; this strain produces at least seven different colony morphologies. In both the WO-1 and 3153A strains, the different phases convert spontaneously to the other(s) at a low frequency. The switching is reversible, and colony type can be inherited from one generation to another. While several [[gene]]s which are [[gene expression|expressed]] differently in different colony morphologies have been identified, some recent efforts have focused on what might be controlling these changes. Further, whether there is a potential molecular link between dimorphism and phenotypic switching is a tantalizing question.
In the 3153A strain, a gene called SIR2 (for silent information regulator) has been found which seems to be important for phenotypic switching. SIR2 was originally found in ''[[Saccharomyces cerevisiae]]'' (brewer's yeast), where it is involved in [[chromosomal silencing]] — a form of [[transcriptional regulation]] in which regions of the [[genome]] are reversibly inactivated by changes in [[chromatin]] structure (chromatin is the complex of [[DNA]] and proteins which make [[chromosomes]]). In yeast, genes involved in the control of mating type are found in these silent regions, and SIR2 represses their expression by maintaining a silent-competent chromatin structure in this region. The discovery of a ''C. albicans'' SIR2 which is implicated in phenotypic switching suggests that it too has silent regions controlled by SIR2, in which the phenotype-specific genes may perhaps reside.
Another potential regulatory molecule is Efg1p, a [[transcription factor]] found in the WO-1 strain which regulates dimorphism, and more recently has been suggested to help regulate phenotypic switching. Efg1p is expressed only in the white and not in the gray cell-type, and overexpression of Efg1p in the gray form causes a rapid conversion to the white form<ref>{{cite journal |author=Sonneborn A, Tebarth B, Ernst J |title=Control of white-opaque phenotypic switching in Candida albicans by the Efg1p morphogenetic regulator |journal=Infect. Immu. |volume=67 |issue=9 |pages=4655-4660 |year=1999}}</ref><ref>{{cite journal |author=Srikantha T, Tsai L, Daniels K, Soll D |title=EFG1 null mutants of Candida albicans switch but cannot express the complete phenotype of white-phase budding cells |journal=J. Bact. |volume=182 |issue=6 |pages=1580-1591 |year=2000}}</ref>.
So far there are few data which say that dimorphism and phenotypic switching use common molecular components. However, it is not inconceivable that phenotypic switching may occur in response to some change in the environment as well as being a spontaneous event. How SIR2 itself is regulated in ''[[Saccharomyces cerevisiae]]'' may yet provide clues as to the switching mechanisms of ''C. albicans''.
==Heterozygosity==
The [[heterozygosity]] of the ''Candida'' genome exceeds that found in other genomes and is widespread among clinical isolates. Non-synonymous [[single nucleotide polymorphism|single base polymorphisms]] result in two proteins that differ in one or several amino acids that may confer functional differences for each protein. This situation considerably increases the number of different proteins encoded by the genome.<ref name=Larriba>{{cite book |chapterurl=http://www.horizonpress.com/pat2|author=Larriba G; Calderone RA|year=2008|chapter=Heterozygosity and Loss of Heterozygosity in Candida albicans |title=Pathogenic Fungi: Insights in Molecular Biology|publisher=Caister Academic Press|id=[http://www.horizonpress.com/pat2 ISBN 978-1-904455-32-5]}}</ref>
== See also ==
*[[Torula|Torula yeast]] (''Candida utilis'')
* [[Undecylenic acid]] (Castor oil derivative) for candida fungus infections.
* [[Leaky gut syndrome]] for damage to the bowel or gut (increased permeability to gut wall or bowel lining).
== References ==
<references/>
*Jones et al. 2004. The diploid genome sequence of ''Candida albicans'' [http://www.pnas.org/cgi/content/full/101/19/7329 ''PNAS'' 101:7329-7334.]
*[http://nar.oxfordjournals.org/cgi/content/full/gkm1010v1 CandidaDB.a multi-genome database for Candida species and related Saccharomycotina]
== External links ==
*[http://www.candidagenome.org/ Candida Genome Database]
*[http://www.ncbi.nih.gov/mapview/map_search.cgi?taxid=5476 U.S. National Institutes of Health on the ''Candida albicans'' genome]
*[http://www.nznature.co.nz/gads/cpn=9998,gotopg=kolorex-wp Causes for candida albicans & Natural Herbal Treatment, FAQ. No clinical tests mentioned.]
*[http://www4.ncbi.nlm.nih.gov/Coffeebreak/CB10_SIR2/page.html# NIH - How ''Candida albicans'' switches phenotype]
*[http://www.broad.mit.edu/annotation/genome/candida_albicans ''Candida albicans'' genome]
*[http://www.horizonpress.com/gateway/candida.html ''Candida'' genomics]
*[http://www.nutritioninstitute.com/7.html Eczema, psoriasis, Chronic Rashes, and their relationship to Candida albicans. Website sells book promoting yeast-free diet. No clinical tests mentioned.]
*[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11413927&dopt=Abstract Incidence of Candida in psoriasis--a study on the fungal flora of psoriatic patients]
*[http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371%2Fjournal.pbio.0050256 Interlocking Transcriptional Feedback Loops Control White-Opaque Switching in Candida albicans]
[[Category:Ascomycota]]
[[Category:Yeasts]]
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