Greg S May, Ph.D.

Research in my laboratory focuses on regulation of fungal cellular physiology that controls growth, conidial germination and polar hyphal growth. We use both the genetically tractable fungus Aspergillus nidulans and the opportunistic pathogen Aspergillus fumigatus. Recent work has focused on the role of mitogen-activated protein kinases (MAPK) in controlling conidial germination and pathogenesis in A. fumigatus. Deletion mutants have been made for the MAPK genes sakA/hogA and mpkC. sakA codes for a highly conserved MAPK that functions to regulate cellular physiology in response to osmotic stress. While the SakA MAPK and its functions are highly conserved in fungi, we demonstrated a novel role for this MAPK in negative regulation of conidial germination in response to the nitrogen source in the medium. In contrast, little is known about the functions of the MAPK MpkC, though it is also found in other fungi. The MpkC also appears to have functions in regulating conidial germination, but its roles in regulating conidial germination are distinct from those of SakA.

My laboratory has developed whole genome DNA microarrays for A. fumigatus in collaboration with investigators at The Institute for Genome Research. Microarrays are being used to look at patterns of gene expression at elevated growth temperatures. A. fumigatus is a thermophilic fungus able to grow up to 55°C. The microarrays are also being used to look at patterns of gene expression in wild-type, and sakA and mpkC mutants in response to a variety of stresses. These are being done to determine how these MAPK genes contribute to cellular homeostasis and the resulting transcriptional responses. The results of these experiments will be used to direct the development of specific deletion mutant strains to determine the role of genes in MAPK signaling pathways and fungal virulence. In addition, in collaboration with TIGR we are using comparative genomics to identify candidate virulence gene regulators. Four Aspergillus genomes have been sequenced, including Neosartorya fischeri, a species taxonomically close to A. fumigatus but also minimally pathogenic. Comparative genome analysis has identified 28 gene differences that are either transcription regulators or protein kinases. These genes are candidates for deletion and analysis of their role in fungal pathogenesis.

Recent publications

Lionakis MS, Lewis RE, May GS, Wiederhold, NP, Albert ND, Halder G, Kontoyiannis DP (2005) Toll-deficient fruit flies as a fast, high-throughput model to study the efficacy of antifungal drugs and virulence in aspergillosis. J. Infect. Dis. 191:1188–1195.
Xiong Q, Hassan SA, Wilson WK, Han XY, May GS, Tarrand JJ, Matsuda SP (2005) Cholesterol import by Aspergillus fumigatus and its influence on antifungal potency of sterol biosynthesis inhibitors. Antimicrob. Agents Chemother. 49:518–524.
Tarrand JJ, Han XY, Kontoyiannis DP, May GS (2005) Aspergillus hyphae in infected tissue: evidence of physiologic adaptation and effect on culture recovery. J. Clin. Microbiol. 43:382–386.
Xue T, Nguyen CK, Romans A, Kontoyiannis DP, May GS (2004) Isogenic auxotrophic mutant strains in the Aspergillus fumigatus genome reference strain AF293. Arch. Microbiol. 182, 346-353.
Wei L, May GS, Lionakis MS, Lewis RE, Kontoyiannis DP (2004) Extra copies of the Aspergillus fumigatus squalene epoxidase gene confer resistance to Terbinafine: Genetic approach to studying gene dose-dependent resistance to antifungals in A. fumigatus. Antimicrob. Agents Chemother. 48, 2490-2496.
Xue T, Nguyen CK, Romans A, May GS (2004) A mitogen-activated protein kinase that senses nitrogen regulates conidial germination and growth in Aspergillus fumigatus. Eukaryot. Cell. 3, 557-560.
Kontoyiannis DP, Lewis RE, Lionakis MS, Albert ND, May GS Raad II (2003) Sequential exposure of Aspergillus fumigatus to itraconazole and caspofungin: evidence of enhanced in vitro activity. Diagnostic Microbiol. Infectious Diseases. 47, 415-419.
Liu W, Lionakis MS, Lewis RE, Wiederhold N, May GS, and Kontoyiannis DP (2003) Attenuation of itraconazole fungicidal activity following preexposure of Aspergillus fumigatus to fluconazole. Antimicrob. Agents Chemother. 47, 3592-3597.
Kontoyiannis DP, Lewis RE, Osherov N, Albert ND, May GS (2003) Combination of caspofungin with inhibitors of the calcineurin pathway attenuates growth in vitro in Aspergillus species. J. Antimicrob. Chemother. 51, 313-16.
Pham AS, Tarrand JJ, May GS, Lee, MS, Kontoyiannis DP, Han XY (2003) Diagnosis of invasive mold infection by real-time quantitative PCR. Am. J. Clin. Pathol, 119, 38-44.
Nozawa SR, May GS, Martinez-Rossi NM, Ferreira-Nozawa MS, Coutinho-Netto J, Maccheroni W, Rossi A (2003) Mutation in a calpain-like protease affects the posttranslational mannosylation of phosphatases in Aspergillus nidulans. Fungal Genet. Biol. 38, 220-227.
Osherov N, Mathew J, Romans A, May GS (2002) Identification of conidial-enriched transcripts in Aspergillus nidulans using suppression subtractive hybridization. Fungal Genet. Biol. 37, 197-204.
Osherov, N., May, G.S., Albert, N.D. and Kontoyiannis, D.P. (2002) Overexpression of Sbe2p, a golgi protein, results in resistance to Caspofungin in Saccharomyces cerevisiae. Antimicrob. Agents Chemother. 46, 2462-2469.
Liu, X., Osherov, N., Yamashita, R., Brzeska, H. Korn, E.D. and May, G.S. (2001) Myosin I mutants with only one percent of wild-type ATPase activity retain in vivo function. Proc. Natl. Acad. Sci. USA. 98, 9122-9127.
Osherov, N. Kontoyiannis, D.P., Romans, A. and May, G.S. (2001) Resistance to itraconazole in Aspergillus nidulans and Aspergillus fumigatus is conferred by extra copies of the Aspergillus nidulans P-450 14a-demethylase gene, pdmA. J. Antimicrob. Chemother 48, 75-81.