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Transcriptome Reveals Stress-Response Machinery in C. neoformans Print E-mail

 

heitmanbahnVirulent pathogens, such as the fungus Cryptococcus neoformans, must be able to adapt to a hostile host environment. Yong-Sun Bahn of Yonsei University, Seoul, Korea, Joseph Heitman of Duke University, Durham, N.C., et al. performed transcriptome analysis in C. neoformans to explore genetics of stress response, both within and without the stress-activated HOG pathway, identifying many stress-response-related genes, including numerous HOG-target genes. They showed that "inhibition of the HOG pathway induces ergosterol biosynthesis genes, which increase cellular ergosterol content," says Bahn. "This finding strongly indicates that an inhibitor of the HOG pathway will have strong, synergistic, anti-cryptococcal effects with amphotericin B, the most widely used treatment for cryptococcosis." And that, he says, suggests that it should be possible to find a new drug that would work in combination therapy with amphotericin B. They are working on developing a screening system for that purpose. Additional discoveries include novel stress defense and HOGdependent genes, which encode a sodium/potassium efflux pump, protein kinase, multidrug transporter system, and elements of the ubiquitin-dependent system.

(Y.-J. Ko, Y. Man Yu, G.-B. Kim, G.-W. Lee, P. J. Maeng, S.-S. Kim, A. Floyd, J. Heitman, and Y.-S. Bahn. 2009. Remodeling of global transcription patterns of Cryptococcus neoformans genes mediated by the stress-activated HOG signaling pathways. Eukaryot. Cell 8:1197-1217.)