Overexpression of the Aspergillus fumigatus Small GTPase, RsrA, Promotes Polarity Establishment during Germination

Cell polarization comprises highly controlled processes and occurs in most eukaryotic organisms. In yeast, the processes of budding, mating and filamentation require coordinated mechanisms leading to polarized growth. Filamentous fungi, such as , are an extreme example of cell polarization, essential for both vegetative and pathogenic growth. A major regulator of polarized growth in yeast is the small GTPase Rsr1, which is essential for bud-site selection. Here, we show that deletion of the putative ortholog, , causes only a modest reduction of growth rate and delay in germ tube emergence. In contrast, overexpression of results in a morphogenesis defect, characterized by a significant delay in polarity establishment followed by the establishment of multiple growth axes. This aberrant phenotype is reversed when expression levels are decreased, suggesting that correct regulation of RsrA activity is crucial for accurate patterning of polarity establishment. Despite this finding, deletion or overexpression of resulted in no changes of virulence attributes in a mouse model of invasive aspergillosis. Additional mutational analyses revealed that RsrA cooperates genetically with the small GTPase, RasA, to support viability.