My Contact Information

Research Associate Professor of Biochemistry and Biophysics
Ph.D. Leningrad State University, U.S.S.R.

Chromosomes instability of human fungal pathogen Candida albicans.  Survival due to specific chromosome rearrangements.

Candida albicans is a unicellular budding fungus that forms part of normal gut or genitalia microflora. In immunocompromized humans, however, C. albicans becomes an important opportunistic pathogen that can cause mortality. C. albicans is unique among other fungal pathogens by having an ability to infect divers sites of human body, including skin, nails, mucosal surfaces, as well as any other tissues or inner organs. In the laboratory, this fungus demonstrates an impressive ability to flourish under extreme pH and temperatures, as well as in other extreme environments. C. albicans possesses an acute ability to counter act the environmental stresses and to mount adequate phenotypic responses.

Over 10 years ago, we made the remarkable discovery that C. albicans evolved an unusual mechanism of survival in adverse environments that cause lethality or inhibit growth. Using four different environments, we demonstrated that this naturally diploid microbe survived in a specific environment by altering a specific chromosome. Alterations included loss and gain of the entire chromosomes or loss and gain of the large portions of chromosomes. For example, survival on the medium containing the toxic sugar L-sorbose involved predominantly the formation of monosomy of chromosome 5 (Ch5), Fig. 1; survival on the medium with an antifungal fluconazole, resulted in the monosomy of Ch4, Fig. 2; survival on the toxic 5-fluoro-orotic acid, resulted in either the duplication of Ch4 or the enlargement of Ch5; and survival on the alternative sugar D-arabinose, resulted in either the monosomy of Ch6 or the trisomy of Ch2, which was coupled with a large deletion. Of these, the loss and gain of one homolog of a chromosome represents a novel form of gene regulation.

Detailed studies of sorbose-utilizing mutants monosomic for Ch5 provided an understanding of some aspects of the mechanism of regulation as based on diminution of chromosome copy number. Ch5 monosomy and re-duplication occur at high frequencies with a high degree of fidelity, which fulfills a requirement for regulatory systems. Ch5 monosomy induces expression of the metabolic gene for sorbose catabolism, SOU1, which is carried on Ch4. The loss of an entire Ch5 is required because Ch5 carries multiple functionally redundant genes for the negative regulators of sorbose utilization that are scattered along the chromosome. Overall, we have suggested that the mode of gene regulation involving large genome rearrangements implies that regulatory and metabolic genes in C. albicans are distributed non-randomly over the chromosomes. An entire chromosome thus, can act as a single regulatory unit, a feature not previously considered.

Recent Publications

Rustchenko E (2007) Specific chromosome alterations of Candida albicans: mechanisms for adaptation to pathogenicity. Evolutionary biology of bacterial and fungal pathogens. Edited by C. Nombela, G. H. Cassel, F. Baquero and J. A. GutiÈrrez-Fuentes. ASM Press, (in press)

Rustchenko E (2007) Chromosome instability in Candida albicans. FEMS Yeast Res, 7:2-11

Andaluz E, Gomez-Raja J, Hermosa B, Ciudad T, Rustchenko E, Calderone R, Larriba G (2007) Loss and fragmentation of chromosome 5 are major events linked to the adaptation of rad52-DeltaDelta strains of Candida albicans to sorbose. Fungal Genet Biol, 44:789-98

Wellington M, Kabir MA, Rustchenko E (2006) 5-fluoro-orotic acid induces chromosome alterations in genetically manipulated strains of Candida albicans. Mycologia, 98:393-8

Greenberg JR, Price NP, Oliver RP, Sherman F, Rustchenko E (2005) Candida albicans SOU1 encodes a sorbose reductase required for L-sorbose utilization. Yeast, 22:957-69

Kabir MA, Rustchenko E (2005) Determination of gaps by contig alignment with telomere-mediated chromosomal fragmentation in Candida albicans. Gene, 345:279-87

Wellington M, Rustchenko E (2005) 5-Fluoro-orotic acid induces chromosome alterations in Candida albicans. Yeast, 22:57-70

Kabir MA, Ahmad A, Greenberg JR, Wang YK, Rustchenko E (2005) Loss and gain of chromosome 5 controls growth of Candida albicans on sorbose due to dispersed redundant negative regulators. Proc Natl Acad Sci U S A, 102:12147-52

Wang YK, Das B, Huber DH, Wellington M, Kabir MA, Sherman F, Rustchenko E (2004) Role of the 14-3-3 protein in carbon metabolism of the pathogenic yeast Candida albicans. Yeast, 21:685-702

Rustchenko E (2007) Chromosome instability in Candida albicans.. FEMS Yeast Research, 7:1-11

Rustchenko E (2007) Specific chromosome alterations of Candida albicans: mechanism for adaptation to pathogenicity. In: Introduction to the evolutionary biology of bacterial and fungal pathogens. Edited by C. Nombela, F. Baquero, J. A. GutiÈrrez-Fuentes, ASM Press, pp. 197-212.

Rustchenko E (2003) Candida albicans adaptability to environmental challenges by means of specific chromosome alteration. Recent Research developments in Bacteriology. Transworld Research Network, Vol. 1, pp. 91-102,

Rustchenko E (2003) Regulation de líexpression des genes par des modifications specifiques des chromosomes. In: Annales de líInstitut Pasteur/Actualites. Les Mycoses. Edited by F. Dromer and O. Lortholary. Elsevier, Amsterdam, publisher, pp. 223-236

Rustchenko E, Sherman F (2002) Genetic instability of Candida albicans. Fungi Pathogenic for Humans and Animals, Second Edition. Edited by D. H. Howard. Marcel Dekker, Inc., Publiser, pp. 723-776

Janbon G, Sherman F, Rustchenko E (1999) Appearance and properties of L-sorbose-utilizing mutants of Candida albicans obtained on a selective plate. Genetics, 153:653-64

Perepnikhatka V, Fischer FJ, Niimi M, Baker RA, Cannon RD, Wang YK, Sherman F, Rustchenko E (1999) Specific chromosome alterations in fluconazole-resistant mutants of Candida albicans. J Bacteriol, 181:4041-9

Janbon G, Sherman F, Rustchenko E (1998) Monosomy of a specific chromosome determines L-sorbose utilization: a novel regulatory mechanism in Candida albicans. Proc Natl Acad Sci U S A, 95:5150-5

Rustchenko-Bulgac EP, Sherman F, Hicks JB (1990) Chromosomal rearrangements associated with morphological mutants provide a means for genetic variation of Candida albicans. J Bacteriol, 172:1276-83

Cluster Affiliation    

Contact Information

E-Mail: Elena_Bulgac@urmc.rochester.edu

Elena Rustchenko-Bulgac
Department of Biochemistry and Biophysics
University of Rochester School of Medicine and Dentistry
601 Elmwood Ave, Box 712
Rochester, New York 14642

Office: Medical Center 6-8818
Telephone: (585) 275-6710; Fax: (585) 271-2683