Multiple chromosomal and phenotypic changes in spontaneous mutants of Candida albicans

Abstract

Previous studies have revealed the occurrence of multiple chromosomal alterations among spontaneous colony form mutants and clinical isolates of Candida albicans. In this report we show that such karyotype alterations are also seen in spontaneous and induced non-germinative mutants of the fungus. To determine if phenotypic changes other than colony form and microscopic morphology accompanied the rearrangements of the electrophoretic karyotype, we studied the following characteristics of the non-germinative and some of the colony form mutants : formation of pseudohyphae, chlamydospore production, germ tube formation, colony morphology, auxotrophy, growth at various temperatures, and colony morphology and pigment formation on selected media (bismuth sulphite and Phloxine B). We established that phenotypic and karyotypic variability among spontaneous, non-germinative mutants was no different than such variability among spontaneous colony form mutants. Thus, non-germination may represent another phenotypic consequence of genomic instability in C. albicans. The variability in different phenotypic attributes that occurred amongst the mutants was not associated with any given karyotype. Moreover, neither the low nor the high phenotypic variabilities observed were explained by the relatively high number of alterations in a limited number of chromosomes.

Transcriptional Regulatory Circuitries in the Human Pathogen Candida albicans Involving Sense–Antisense Interactions

“…Also, we used the well-characterized prototrophic Sou 2 strain 3153A (Rustchenko-Bulgac and Howard 1993). The strains carrying in their genome either a control empty vector pAK156 or a vector with one ASU53, pEA249, or two ASU53s, pEA254, were prepared by individually integrating the plasmids into the LEU2 locus on Ch7.…”

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

“…1. The electrophoretic karyotypes of 46 of the 106 spontaneous morphological mutants were characterized previously and each mutant was found to be uniquely altered (Rustchenko-Bulgac et al, 1990 ;RustchenkoBulgac, 1991 ;Rustchenko-Bulgac & Howard, 1993). Some of these mutants represent a series of sequentially derived subclones having continually variable electrophoretic karyotypes and morphological phenotypes (Rustchenko-Bulgac, 1991).…”

“…1: ml-m20 and m5OO were derived directly from 3153A during growth on glucose medium and were detected on LBC medium (Lee et al, 1975) by the altered appearance of their colonies (Rustchenko-Bulgac et al, 1990;Rustchenko-Bulgac, 1991) ; descendants derived spontaneously from m14 and m.500 by multiple rounds of subcloning (Rustchenko-Bulgac, 1991) ; strain 300, an unstable variant of 3153A (Rustchenko-Bulgac & Howard, 1993) ; and spontaneous mutants 301,302,303 and 300-SG derived from 300, originally detected because of their inability to germinate (further studies revealed that they could also be considered morphological mutants ; Rustchenko-Bulgac & Howard, 1993). The 106 morphological mutants used in this study are also listed in Table 5.…”

“…Although many phenotypes were found initially to be affected in these mutants, these traits, such as altered colony or cell morphology, did not appear to be advantageous for the organism. Also, other alterations appeared to be the results of diminished or destroyed functions, such as the inability to form germ tubes or chlamydospores (Rustchenko-Bulgac & Howard, 1993), as well as diminution of adherence (C. Haidaris, University of Rochester, NY, unpublished results) and virulence (E. DiDomenico, Schering Plough Research, Bloomfield, N J, unpublished results), appearing in some, but not all mutants.…”

An increase in switching frequency correlates with an increase in recombination of the ribosomal chromosomes of Candida albicans strain 3153A

“…However, it is important to note that in no study has there been a direct correlation between a colony morphology, a specific change in phenotype, and a specific chromosomal rearrangement (Suzuki e t al., 1989 ;Rustchenko-Bulgac e t al., 1990;Rustchenko-Bulgac, 1991 ;Iwaguchi e t al., 1992;Rustchenko-Bulgac & Howard, 1993).…”