특별세미나_조용준 박사님(서울대학교 기초과학연구원)

서울대학교 기초과학연구원의 조용준 박사님을 모시고 세미나를 진행하려고 합니다. 

온라인과 오프라인(의생명과학대학 B동 128호)을 병행하여 진행합니다. 

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시간은 2020년 12월 8일(화) 오후2시입니다. 

Resistance to Antifungal Agents: Genomic Study of Opportunistic and Pathogenic Skin Fungi Malassezia spp.

조용준 박사(서울대학교 기초과학연구원)

Malassezia spp. is an opportunistic fungal pathogen on animal skin; it is associated with various skin diseases, including seborrheic dermatitis and dandruff, which are usually treated using ketoconazole and zinc pyrithione (ZPT). The mechanism of antifungal agents has been investigated in several studies; however, a non-pathogenic model yeast, such as Saccharomyces cerevisiae was most often used. The aim of the present studies was to understand how antifungal agents inhibits the growth of Malassezia spp. To understand the mechanisms of ketoconazole resistance in the M. restricta isolates, their genomes were sequenced and compared with the susceptible reference strain. Using comparative genome analysis, we identified tandem multiplications of the genomic loci containing ATM1 and ERG11 homologs and other genes involved in ergosterol synthesis, mitochondrial iron metabolism, oxidative stress response and overexpression of the drug efflux pumps in ketoconazole-resistant isolates. Also, we found that M. pachydermatis underwent extensive chromosomal rearrangement to adapt to the pressure of ketoconazole, which has resulted in increased expression levels of the genes involved in the pathway targeted by the drug. Our data suggest that chromosomal rearrangement might be one of the strategies of Malassezia spp. to survive in the presence of high concentrations of antifungal agents. And we analyzed the cellular metal content and transcriptome profile of ZPT-treated M. restricta cells and found that ZPT treatment dramatically increased cellular zinc levels, along with a small increase in cellular copper levels. Moreover, our transcriptome analysis showed that ZPT inhibits Fe-S cluster synthesis in M. restricta. We also observed that ZPT treatment significantly reduced the expression of lipases, whose activities contribute to the survival and virulence of M. restricta on human skin. Therefore, the results of our study suggest that three inhibitory mechanisms are associated with the action of ZPT against M. restricta: (i) an increase in cellular zinc levels, (ii) inhibition of mitochondrial function, and (iii) a decrease in lipase expression.

학력 및 약력

2001         서울대학교 미생물학과(이학사)

2009         서울대학교 생명과학부(이학박사)

2009-2011   서울대학교 미생물연구소(선임연구원)

2011-2016   ㈜천랩(책임연구원)

2017-2019   극지연구소(선임연구원)

2019-현재    서울대학교 기초과학연구원(연구교수)

주요발표논문 (최근)

Park, M.*, Cho, Y.J.*, Lee, Y.W., and Jung, W.H. (2020). Genomic Multiplication and Drug Efflux Influence Ketoconazole Resistance in Malassezia restricta. Front Cell Infect Microbiol 10, 191.

Park, S.*, Cho, Y.J.*, Jung, D.Y., Jo, K.N., Lee, E.J., and Lee, J.S. (2020). Microbial Diversity in Moonmilk of Baeg-nyong Cave, Korean CZO. Front Microbiol 11, 613.

Do, E., Cho, Y.J., Kim, D., Kronstad, J.W., and Jung, W.H. (2020). A Transcriptional Regulatory Map of Iron Homeostasis Reveals a New Control Circuit for Capsule Formation in Cryptococcus neoformans. Genetics.

Lee, J., Cho, J., Cho, Y.J., Cho, A., Woo, J., Lee, J., Hong, S.G., Sul, W.J., and Kim, O.S. (2019). The latitudinal gradient in rock-inhabiting bacterial community compositions in Victoria Land, Antarctica. Sci Total Environ 657, 731-738.

Su, H., Tissera, K., Jang, S., Choi, Y.H., Kim, A., Cho, Y.J., Li, M., Gunawardhana, N., Merrell, D.S., Ge, L., and Cha, J.H. (2019). Evolutionary mechanism leading to the multi-cagA genotype in Helicobacter pylori. Sci Rep 9, 11203.