Mating in C albicans

The C. albicans Mating Type-Like (MTL) locus was originally described by Hull & Johnson (1999). Homologues of S. cerevisiae mating pathway genes have also been identified in the C. albicans genome (Tzung et al., 2001). The majority of C. albicans isolates are heterozygous at the MTL locus, with only a minority (1011%) homozygous a or a (Legrand et al., 2004; Tavanti et al., 2005). It has subsequently been shown that these homozygous strains are capable of switching between white and opaque forms (Lockhart et al., 2002), and it is opaque cells that are highly competent for mating (Miller & Johnson, 2002). Mating in C. albicans has been the subject of several reviews (Hull & Heitman, 2002; Johnson, 2003; Soll et al., 2003; Soll, 2004).

The cell biology of the mating process is beautifully described by Lockhart et al. (2003a). Analysis of gene expression changes occurring during mating has shown that there are several different categories of genes regulated during mating, some opaque switch-dependent and some opaque switch-independent (Lockhart et al., 2003b).

Opaque cells were previously shown to possess a unique morphology; elongated cells with pimples on the surface (Anderson & Soll, 1987). Opaque cells have since also been shown to have unique transcription patterns (Lan et al., 2002; Lockhart et al., 2003b; Zhao et al., 2005), with differences in metabolic patterns; opaque cells expressing genes associated with oxidative metabolism and white cells expressing a more fermentative profile (Lan et al., 2002). During mating genes involved in filamentation are upregulated and opaque-specific genes downregu-lated in C. albicans (Zhao et al., 2005).

Histone deacetylases have been shown to have a role in phase-specific gene expression (Srikantha et al., 2001), with transcription of two deacetylases, HDA1 and RPD3 being reduced in opaque phase cells (Srikantha et al., 2001). HDA1 deletion increased switching from white to opaque and reduced EFG1 expression, while RPD3 deletion resulted in increased switching frequencies in both directions, and was associated with reduced expression of a number of opaque-specific genes and reduced EFG1 expression (Srikantha et al., 2001). Expression of EFG1 in opaque phase cells induced conversion back to the white form (Sonneborn et al., 1999). TUP1 has also been implicated in white-opaque switching (Zhao et al., 2002), although tup1 null mutants still undergo switching and mate successfully (Park & Morschhauser, 2005a).

A master regulator of white-opaque switching was recently identified, WOR1/ TOS9 (Huang et al., 2006; Srikantha et al., 2006). WOR1 was found to be expressed at low levels in white cells, but in opaque cells forms a positive feedback loop, binding elements in its own promoter to maintain high levels of WOR1 expression (Zordan et al., 2006). Misexpression of WOR1 induced white cells to become stably opaque (Huang et al., 2006; Srikantha et al., 2006). This effect occurs not only in a and a cells, but also in a/a heterozygotes (Huang et al., 2006).

An essential C. albicans gene, HBR1, identified due to its induced expression in response to haemoglobin (Pendrak et al., 2004), has also been found to affect white-opaque switching. Deletion of one copy of the gene allowed opaque-phase switching and mating competence in an MTL heterozygous strain, leading to the suggestion that this may allow mating to occur without allelic deletion at the MTL locus (Pendrak et al., 2004). However, it should be noted that C. albicans strains can become homozygous at the MTL locus via loss of one chromosome 5, followed by duplication of the remaining copy (Legrand et al., 2004; Wu et al., 2005).

Mating in C. albicans is thought to occur on skin, where the lower temperature aids the switch to opaque cells, and responses to the surface topography facilitate mating (Lachke et al., 2003). The result of sex between two C. albicans cells of opposite mating type is a tetraploid cell (Lockhart et al., 2003a). These cells have been shown to lose chromosomes to become diploid once again (Bennett & Johnson, 2003). Tetraploids are less virulent than diploids in a mouse model of infection and have been shown to undergo ploidy changes during infection (Ibrahim et al., 2005). However, MTL homozygosity does not appear to affect virulence (Ibrahim et al., 2005), although this may depend upon C. albicans strain (Lockhart et al., 2005). There may be a possible immunological advantage to being able to switch between white and opaque cells, as opaque cells, unlike white cells, do not secrete a chemoattractant for PMNs (Geiger et al., 2004). Recent research also points to a role of C. albicans opaque cells in biofilm formation (see below) (Daniels et al., 2006). It has been suggested that the mating process in C. albicans may have evolved to allow survival in the host (Bennett & Johnson, 2005), although there is some evidence from MLST studies that sex may allow some recombination in C. albicans (Tavanti et al., 2004; Odds et al., 2006).

Cure Your Yeast Infection For Good

Cure Your Yeast Infection For Good

The term vaginitis is one that is applied to any inflammation or infection of the vagina, and there are many different conditions that are categorized together under this ‘broad’ heading, including bacterial vaginosis, trichomoniasis and non-infectious vaginitis.

Get My Free Ebook


Post a comment