Variation in assimilating functions occurs in spontaneous Candida albicans mutants having chromosomal alterations

Abstract

In this study, four clinical isolates and over 100 colony morphology mutants, previously derived spontaneously from strain 31 53A during growth on glucose medium, were examined for their utilization of 21 carbon and 3 nitrogen sources at various growth temperatures. The results demonstrated extensive variability in the pattern of assimilation among the mutants and strains, including both the gain and loss of assimilating functions. The persistent alterations in assimilation patterns observed in sequentially produced subclones illustrated an extensive ability of C. albicans populations to constantly produce new combinations of assimilating functions. The variability among spontaneous mutants derived from a single strain explains the well documented variability among natural isolates. From these results we established a relationship between the previously documented broad spectrum of spontaneous chromosomal aberrations in these mutants to the expression of genes controlling the utilization of alternative carbon and nitrogen sources. The existence of cryptic genes, responsible for growth on alternative substrates, was previously deduced from the analysis of other mutants obtained as a response to the restrictive condition on media containing non-assimilating carbon sources. Thus, mutants with altered assimilation functions can arise either on glucose medium or by selection on restricted media. Extensive differences between the patterns of chromosomal aberrations and the distribution of correlated phenotypes in the two groups of mutants indicated that the same phenotypes may be produced by two different mechanisms involving the same or different genes.

Transcriptional Regulators Cph1p and Efg1p Mediate Activation of the Candida albicans Virulence Gene SAP5 during Infection

“…In addition, a change from heterozygosity to homozygosity for the SAP2 gene occurred during the construction of strain CFI3, which was derived from efg1 mutant HLC67. Such changes may be induced by genetic manipulation of strains (transformation, fluoroorotic acid selection) but may also occur due to natural genomic alterations (26,27). These changes were detected only later when the reporter fusions were introduced into the loci and only because we made efforts to distinguish between the two alleles of the target locus.…”

Multiple LTR-Retrotransposon Families in the Asexual Yeast Candida albicans

“…In addition to its medical importance, C. albicans is of interest because it is diploid and asexual (Scherer and Magee 1990), yet often displays a high level of interstrain variation-by various criteria including pathogenicity (Cutler 1991), karyotype (Iwaguchi et al 1990), and ability to utilize various carbon sources (Rustchenko et al 1997). These factors are contributing to its use as a model system for studying both the means by which genetic variation can be introduced in the absence of meiotic recombination, and the long-term effects of asexuality.…”

Genetic and phenotypic intra-species variation in Candida albicans

“…For example, homozygosis of hyperactive alleles of ERG11, TAC1, and MRR1 (encoding the target of azole drugs or transcription factors regulating drug efflux pumps) can result in strains with increased azole resistance (White 1997;Coste et al 2006;Dunkel et al 2008). Both LOH and karyotypic changes are induced in response to environmental stimuli including drug treatment, heat shock, nutrient utilization, and oxidative stress (Rustchenko et al 1997;Janbon et al 1998;Forche et al 2011;Harrison et al 2014).…”