The Ras and cAMP pathways control growth, differentiation, and virulence of pathogenic fungi, including Cryptococcus neoformans, which causes lethal fungal meningitis.
 But these pathways are only partially mapped. Yong-Sun Bahn of Yonsei University, Seoul, Korea, et al. have discovered novel target genes and innovative features in each. Most notably, mutants from both exhibited hypersensitivity to amphotericin B without affecting ergosterol biosynthesis, suggesting a novel antifungal combination therapeutic method. Confirming their previous research (Journal Highlights, Sept. 2009), this team showed that inhibition of the cAMP pathway confers synergistic anticryptococcal effects with amphotericin B, says Bahn. Simultaneous inhibition of the two pathways resulted in far greater sensitivity to amphotericin B than inhibition of each pathway alone, "indicating that each independently controls polyene drug sensitivity," says Bahn. The research is generally applicable since Ras/cAMP is so widely distributed in fungal pathogens, and here is yet another example of using a genomics study employing a DNA microarray to develop a new idea for drug development.
(S. Maeng, Y.-J. Ko, G.-B. Kim, K.-W. Jung, A. Floyd, J. Heitman, and Y.-S. Bahn. 2010. Comparative transcriptome analysis reveals novel roles of the Ras and cyclic AMP signaling pathways in environmental stress response and antifungal drug sensitivity in Cryptococcus neoformans. Eukaryot. Cell 9:360-378.)
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