A Microbial Biorealm page on the genus Candida dubliniensis
Higher order taxa
Fungi, Ascomycota, Saccharomycetes, Saccharomycetales, Saccharomycetaceae, Candida, Candida dubliniensis
Description and significance
Only approaching its teen years since it was discovered in 1995, in Dublin, Ireland, where it at least partially acquired its name, Candida dubliniensis emerges distinctly separate from its long time mistaken identity as Candida albicans (1). As both reside in the Fungi kingdom, Candida dubliniensis has raised in importance over its significantly more common counterpart, Candida albicans, as a more brutal, opportunistic yeast pathogen (11). Its importance has been clearly visible from its discovery when it was initially associated primarily with HIV patients, as it was originally discovered in them (5). Extensive studies were able to broaden the range of its victims to immunocompromised patients and finally to several healthy individuals, although a minute minority (5, 6).
Although among the Candida fungi C. albicans seems to be the dominant species among infected people, C. dubliniensis is demanding awareness because of its unique characteristics. Even after its discovery, differentiating between C. dubliniensis and C. albicans has been difficult in research studies. Even current studies are trying to determine novel techniques to pinpoint exact species in affected humans. Phenotypic attributes were used originally to describe the identity of the species when they occur in visible areas such as oral cavities. However, due to inconsistencies along with other less observable areas such as respiratory, urine, or stool samples, different means were conducted (8).
Temperature seems to be used as one of the most fundamental tools in identifying C. dubliniensis from C. albicans. C. dubliniensis has the ability to grow and remain functional in temperatures 25 degrees Celsius to 37 degrees Celsius, where as C. albicans would typically be unable to survive in that temperature range (9). The significance in classifying which specie it is rests on the drugs needed to fight off the infection. With C. dubliniensis, there is a built up resistance against azole drugs such as fluconzazole (7). Without proper identification, certain patients would remain untreated if the wrong drug were distributed.
Genomic sequencing for Candida dubliniensis is still in progress and in its opening stages. Candida albicans, however, has gone under limited sequencing, although difficult due to polymorphism. What is known about Candida albicans is that it is a diploid and is 15.6 Mb (10). Again, due to the difficulty of its structure to determine accurate sequencing, it was predicted that it contained 404 genes (10). Based upon less complex studies, certain facts were derived about C. dubliniensis. The table below summarizes the key differences between C. albicans and C. dubliniensis on the genomic level (11).
C. albicans C. dubliniensis Ploidy Diploid Diploid Karyotype pattern 8 bands 9–11 bands Estimated RPS clusters 26 61 Hybridisation to 27A probe Strong Weak Hybridisation to Cd25 probe None Strong Mating loci Present Present SAP genes 10 genes 8 genes ALS genes 8 genes 3 genes at least
A recent method used to distinguish C. albicans from C. dubliniensis is to look for the small nucleotide sequence of the ribosomal gene (13). All the species of Candida show a resemblance to one another, but there still remains a strong enough difference between them to single out C. dubliniensis if it were present. And although the similarity between C. albicans and C. dubliniensis is the most common of any Candida specie, comparisons of the sequence show identical introns except for two deviating tem-loop regions (1). In addition, the two located drug resistant genes of C. dubliniensis are CDR1 and CDR2 which allow for further identification (14).
Cell structure and metabolism
Candida dubliniensis is a dimorphic fungus which grants it the ability to serve as a pathogen in humans. Its cell walls include mannan, glucan, and small amounts of chitin (2). Another feature of C. dubliniensis is its cell wall. According to recent studies, the results show the cell surface is constantly hydrophobic (9). This is just one other method that can be used to identify it when it is in the presence of C. albicans.
C. dubliniensis has a metabolism similar to other yeast where it uses amino acids for cell wall growth and breakdown. In addition, the differentiation of C. dubliniensis from C. albicans continues with evidence of C. dubliniensis strains with the ability to produce significantly higher amounts of chlamydospores (1). This is a preliminary means of identification along when the green pathogen is spotted. It is typically followed by temperature analysis to make further accurate determinations.
Within HIV-infected patients, C. dubliniensis appeared in oral cavities, terming the condition candidosis (1). Besides contaminating oral cavities, the fungus has been observed through other means. It has been found in fecal matter, urine, and vaginal discharges causing oropharyngeal, vaginal and bloodstream infections (6).
The key significance of Candida dubliniensis is attributed to its classification as a pathogen. In studies of HIV-infected patients, approximately one-fifth also tested positive for C. dubliniensis (12). The dangers of are even greater than its counterpart, C. albicans, which affects even a greater amount of HIV-infected patients. However, C. dubliniensis has genes which construct it to have resistance against azole drugs such as fluconazole (12). And although rare, C. dubliniensis does also infect non-HIV-infected healthy individuals. But the fungus is not limited to predominantly HIV-infected individuals. People with cancer and other underlying conditions also tested positive for C. dubliniensis, indicating the pathogen mainly targets immunocompromised subjects (6).
New drugs are in the process of being perfected to halt the development of the cell wall within the fungi. Some new drugs hope to target the production of glucan and mannan of the cell wall while others target the resistant genes directly (14).
Application to Biotechnology
As of this moment, Candida dubliniensis serves no beneficial purpose to society. Its pathogenic characteristics are currently still being fought in order to eliminate its dangerous affects on humans. And although once thought to be a sole affecter of immunocompromised individuals, there is a rise in concern due to its ability to also infect healthy subjects.
Recent research is still being conducted in hopes of finding a permanent means of dealing with Candida dubliniensis and its resistance to certain drugs. Just within the last year, a Japanese university has taken the steps to specifically target the areas which allow the fungus to have resistance. They have observed that an ATP efflux inactivates the CDR1 and CDR2 genes which are responsible for drug resistance (14). Without the proper energy to activate the pump to rid of the antifungal agents, the resistance itself is in fact inoperable. The research team has also tried targeting other areas, such as stopping the production of mannan and glucan to prevent the structure of the cell wall. However, their main results show the cooperation between peptides and antifungal drugs. The results of this research will be used to treat other fungal and possible bacterial microbes that have drug resistant qualities (14).
Another research team is in search of all of the victims of Candida dubliniensis. The team’s goal is to determine if fungal strains that are pathogenic to humans can also be found in animals. In a recent study, they tested sea birds and ticks and found both to be positive for strands of Candida. The sea birds had Candida albicans while the ticks had both Candida dubliniensis and Candida albicans (15). This initial step has determined that animals can in fact also carry the same fungal species as the ones infecting humans. With more information and further research, the way pathogens are treated could be revolutionized with better understanding through animals which may remain unaffected by the fungi.
Researchers at the faculty of medicine in Kuwait University came upon a discovery in 2005. The research team discovered Candida dubliniensis in the first HIV-negative patients in Kuwait along with perhaps the first recorded case of the fungus in the Persian Gulf (6). Their research is further a testimony of the dangers of Candida dubliniensis in people who are also not affected by HIV. Although negative for HIV, the patients had been positive for cancer, lupus, and diabetes. These findings can help determine if Candida dubliniensis can affect all immunosuppressed patients or if it has it has limits which can be taken advantage of. Ongoing research will help yield the limitations of this fungus and its reach within the human race.
(1) Sullivan D, Moran G, Donnelly S, Gee S, Pinjon E, McCartan B, Shanley D and Coleman D. “Candida dubliniensis: An update.” Revista Iberoamericana de Micología. 1999; Rev Iberoam Micol 1999; 16: 72-76. http://www.reviberoammicol.com/1999-16/072076.pdf
(2) Barrette-Bee KJ, Lees J, Henderson W. “Variation in the activities of enzymes associated with cell wall metabolism during a growth cycle of Candida albicans.” Elsevier Biomedical Press. 1982 May. FEMS Microbiology Letters 15 275-278. http://www.blackwell-synergy.com/doi/pdf/10.1111/j.1574-6968.1982.tb00233.x
(3) Candida dubliniensis, genus, Candida NCBI reference: http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi
(4) Candida dubliniensis, Dr. Fungus reference: http://www.doctorfungus.org/thefungi/img/cand_dubl_chlamydospore.jpg
(5) Coleman D, Sullivan D, Bennett D, Moran G, Barry H, Shanley D. “Candidiasis: the emergence of a novel species, Candida dubliniensis.” AIDS. 1997; 11: 557–567.
(6) Ahmad S, Khan Z, Mokaddas E, Khan Z. “Isolation and molecular identification of Candida dubliniensis from non-human immunodeficiency virus-infected patients in Kuwait.” Journal of Medical Microbiology. 2004; 53, 633–637.
(7) Moran G, Sullivan D, Morschha J, Coleman D. “The Candida dubliniensis CdCDR1 Gene Is Not Essential for Fluconazole Resistance.”ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2002 Sept. 2829–2941.
(8) Sullivan D, Coleman D. “Candida dubliniensis: Characteristics and Identification” Journal of Clinical Microbiology. 1998 Feb. 329–334.
(9) Jabra-Rizk M, Falkler W, Merz W, Kelley J, Baquil A, Meiller T.“Candida dubliniensis and Candida albicans display surface variations consistent with observed intergeneric coaggregation.” http://www.reviberoammicol.com/1999-16/187193.pdf
(10) Chibana H, Oka N, Nakayama H, Aoyama T, Magee B, Magee P, Mikami Y. “Sequence Finishing and Gene Mapping for Candida albicans Chromosome 7 and Syntenic Analysis Against the Saccharomyces cerevisiae Genome.” Genetics. 2005 August; 170(4): 1525–1537. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=15937140
(11) Sullivan D, Moran G, Coleman D. “Candida dubliniensis: Ten years on.” FEMS Microbiology Letters 253 (2005) 9–17.
(12) Tintelnot K, Haase G, Seibold M, Bergmann F, Staemmler M, Franz T, Naumann D. “Evaluation of Phenotypic Markers for Selection and Identification of Candida Dubliniensis.” Journal of Clinical Microbiology. 2000 Apr. 1599–1608.
(13) Gilfillan G, Sullivan D, Haynes K, Parkinson T, Coleman D, Gow N. “Candida dubliniensis: phylogeny and putative virulence factors.” Microbiology. 1998. 144, 829–838.
(14) Tanida T, Okamoto T, Ueta E, Yamamoto T, Osaki T. “Antimicrobial peptides enhance the candidacidal activity of antifungal drugs by promoting the efflux of ATP from Candida cells.” Journal of Antimicrobial Chemotherapy. 2006. 57, 94–103.
(15) Nunn M, Schafer S, Petrou M, Brown J. “Environmental source of Candida dubliniensis.” Emerging Infectious Diseases. 2007 May. http://findarticles.com/p/articles/mi_m0GVK/is_5_13/ai_n19170750/pg_1
Edited by Arash Tebbi, student of Rachel Larsen
Edited by KLB