Pathways Regulating Mating and Virulence

During infection, Cn cells grow as haploid-budding yeast. However, like other members of the fungal kingdom, Cn can also undergo mating and meiosis to produce spores. This process is not observed in vivo, but occurs in vitro under specific conditions, and presumably occurs in the environment. The mating process involves complex morphological transitions and regulatory mechanisms. Interestingly, some

Table 6.2 Oxidative stress factors that affect virulence

Factor References

Thiol-specific Antioxidant Missall et al. (2004)

Thioredoxin Missall and Lodge (2005)

Skn7 Coenjaerts et al. (2006), Wormley et al. (2005)

Superoxide dismutase Giles et al. (2005), Narasipura et al. (2003)

Alternative oxidase Akhter et al. (2003)

of the factors controlling mating also contribute to virulence. For example, signal transduction factors involved in mating regulation also influence virulence. These include factors involved in MAPK signaling, such as components of the HOG (high osmolarity glycerol) pathway, which controls the stress response (Bahn et al., 2005, 2006). Members of the PAK (p21 GTPase activated kinase) family, such as STE20a, STE20a, and PAK1 also play a role in virulence (Nichols et al., 2004; Wang et al., 2002). Lastly, the Cn Rasl homolog, a GTP-binding protein, contributes to virulence and regulates mating filamentation (Alspaugh et al., 2000).

Other examples of mating factors that contribute to virulence are the mating pheromone receptor and the mating pheromone (MFa). Deletion of CPRa, encoding the receptor, results in total loss of virulence in mice and smaller capsule size in vivo (Chang et al., 2003). However, deletion of the MFa gene has only a slight effect on virulence in mice (Shen et al., 2002). STE12a and STE12a are transcription factor genes located within the mating loci (MATa and MATa) that control mating in Cn. Deletion of these genes results in either attenuation or total loss of virulence in mouse models of infection. Furthermore, known virulence attributes of Cn are reduced in the deletion mutants, including melanin, capsule, and PLB activity. However, the degree of attenuation and virulence factor effects is strain dependent (Chang et al., 2001; Davidson et al., 2003; Ren et al., 2006). In addition, not all of the factors regulating mating are also required for virulence (e.g. Sxila and Sxi2a) (Hull et al., 2005). The variability of effects on virulence shows that the relationship between mating and virulence is complex.

Besides the role of specific mating factors in virulence, mating has another significant influence on virulence: generation of virulent Cn strains through genetic recombination. A prominent example of this is the Cn strains causing the current outbreak of cryptococcosis in Vancouver. Genetic analyses of the outbreak strains suggest they arose from recombination between an endemic strain and more virulent strain from Australia (Fraser et al., 2005).

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.

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