Asexual Development

Under the appropriate environmental conditions, P. marneffei undergoes asexual development at 25°C resulting in the production of conidia. The molecular mechanisms which control conidiation are best understood in the monomorphic non-pathogenic fungus A. nidulans where a cascade of transcriptional regulators functions downstream of the inductive signals to effect the developmental programme (Clutterbuck, 1969): brlA, which encodes a C2H2 zinc finger protein (Adams et al., 1988), activates the expression of abaA, which encodes an ATTS/TEA protein (Andrianopoulos & Timberlake, 1994; Burglin, 1991) and in turn, AbaA activates the expression of wetA, which encodes a spore-specific protein (Marshall & Timberlake, 1991) and feedback regulates its own expression and that of brlA (Mirabito et al., 1989). In P. marneffei, asexual development is similarly regulated by BrlA and AbaA (Figure 9.4) (Borneman et al., 2000, 2002b). In addition, AbaA also plays an important role in yeast morphogenesis (Borneman et al., 2000).

Multiple controls impinge on the central cascade of transcriptional activators to modulate its activity (Adams et al., 1998). The stuA gene, encoding a member of the APSES family of transcriptional regulators, is required for the formation of sterigmata cells (metulae and phialides), but not for the production of conidia and is a regulator of brlA and abaA (Borneman et al., 2002a). The tupA gene, encoding a WD40 repeat protein homologous to the S. cerevisiae TUP1 co-repressor gene, promotes filamentation and represses asexual development in a BrlA-dependent manner (Figure 9.4) (Todd et al., 2003). TupA activity is also required to repress yeast morphogenesis by an unknown mechanism (Todd et al., 2003). In addition to these transcriptional controls, morphogenesis of the cell types in the P. marneffei conidiophore is dependent on a Rac-like small GTPase encoded by cflB which controls cell polarization and separation. CflB also plays a role during hyphal, but not yeast, morphogenesis (Boyce et al., 2003).

Preceding the regulatory cascade are two Ga subunits of the heterotrimeric G protein complexes and a Ras small GTPase, all of which have multiple roles. The GasA Gasubunit plays a role in asexual development at 25°C by repressing brlA expression, possibly via a cAMP-PKA cascade, and thereby promoting vegetative growth (Zuber et al., 2002). It also plays a minor role in the regulation of secondary metabolism. In contrast, the GasC Gasubunit has a significant effect on secondary metabolism and a minor effect during asexual development (Zuber et al., 2003). GasC also has a profound role in controlling conidial germination

Asexual Development

250C

Conidiophore Hyphae

GasA StuA I Ga bHLH \ 1 BrlA

Dimorphic switching

AbaA

ATTS

Yeast

Yeast

GasA StuA I Ga bHLH \ 1 BrlA

AbaA

ATTS

Figure 9.4 Proposed transcriptional regulatory circuit controlling asexual development and dimorphic switching in P. marneffei. When vegetative hyphae are exposed to the appropriate cues, asexual development is initiated. This requires removal of the negative influences of the Ga subunit GasA, the WD40-containing TupA proteins, and the predicted switch regulator which act on the brlA gene. BrlA (C2H2 transcriptional activator) activates AbaA (ATTS transcriptional activator) and, in concert, are required for differentiation of the conidiophore. When cells are grown at 37°C, the hyphal to yeast dimorphic switch is initiated by the predicted switch regulator and requires removal of the negative effects of TupA. Correct yeast cell morphogenesis requires the positive action of the AbaA

Figure 9.4 Proposed transcriptional regulatory circuit controlling asexual development and dimorphic switching in P. marneffei. When vegetative hyphae are exposed to the appropriate cues, asexual development is initiated. This requires removal of the negative influences of the Ga subunit GasA, the WD40-containing TupA proteins, and the predicted switch regulator which act on the brlA gene. BrlA (C2H2 transcriptional activator) activates AbaA (ATTS transcriptional activator) and, in concert, are required for differentiation of the conidiophore. When cells are grown at 37°C, the hyphal to yeast dimorphic switch is initiated by the predicted switch regulator and requires removal of the negative effects of TupA. Correct yeast cell morphogenesis requires the positive action of the AbaA

(Zuber et al., 2003). The RasA small GTPase functions at the onset of asexual development, controlling the timing and the extent of conidiation (Boyce et al., 2005). In addition, mutations in rasA affect conidial germination and hyphal and yeast cell morphogenesis (Boyce et al., 2005).

Was this article helpful?

0 0
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