Molecular Biology and its Application to Medical Mycology NATO ASI Series Advanced Science Institutes Series A series presenting the results of activities sponsored by the NA TO Science Committee, which aims at the dissemination of advanced scientific and technological knowledge, with a view to strengthening links between scientific communities. The Series is published by an international board of publishers in conjunction with the NATO Scientific Affairs Division A Life Sciences Plenum Publishing Corporation B Physics London and New York C Mathematical and Kluwer Academic Publishers Physical Sciences Dordrecht, Boston and London o Behavioural and Social Sciences E Applied Sciences F Computer and Springer-Verlag Systems Sciences Berlin Heidelberg New York G Ecological Sciences London Paris Tokyo Hong Kong H Cell Biology Barcelona Budapest I Global Environmental Change NATO-PCO DATABASE The electronic index to the NATO ASI Series provides full bibliographical references (with keywords and/or abstracts) to more than 30000 contributions from international scientists published in all sections of the NATO ASI Series. Access to the NATO-PCO DATABASE compiled by the NATO Publication Coordination Office is possible in two ways: - via online FILE 128 (NATO-PCO DATABASE) hosted by ESRIN, Via Galileo Galilei, 1-00044 Frascati, Italy. - via CD-ROM "NATO-PCO DATABASE" with user-friendly retrieval software in English, French and German (© WTV GmbH and DATAWARE Technologies Inc. 1989). The CD-ROM can be ordered through any member of the Board of Publishers or through NATO-PCO, Overijse, Belgium. Series H: Cell Biology, Vol. 69 Molecular Biology and its Application to Medical Mycology Edited by Bruno Maresca International Institute of Genetics and Biophysics Via Marconi 12, 80125 Naples, Italy George S. Kobayashi Washington University School of Medicine Division of Infectious Diseases St. Louis, Missouri 63110, USA Hideyo Yamaguchi Research Center for Medical Mycology Teikyo University School of Medicine 359 Otsuka, Hachioji-shi, Tokyo 192-03, Japan Springer-Verlag Berlin Heidelberg New York London Paris Tokyo Hong Kong Barcelona Budapest Published in cooperation with NATO Scientific Affairs Division Proceedings of the NATO Advanced Research Workshop on Molecular Biology and its Application to Medical Mycology, held at Taormina, Italy, January 6-8, 1992 Book design by Donatella Capone, Secretary 11GB Press, Naples, Italy ISBN -13 :978-3-642-84627 -4 e-ISBN-13 :978-3-642-84625-0 DOl: 10.1007/978-3-642-84625-0 Library of Congress Cataloglng-In-Publicatlon Data Molecular biology and Its applicatIOn to medical mycology / edited by Bruno Maresca, and George S Kobayashi, and Hldeyo Yamaguchi (NATO ASI series Series H, Cell biology, vol 69) "Proceedings of the NATO Advanced Research Workshop on Molecular Biology and Its Application to Medical Mycology, held at Taormina, Italy, January 6-8, 1992" ~ Tp verso Includes bibliographical references and Index 1 Medical mycology~Congresses 2 Molecular blology~Congresses 3 Mycoses~Molecular aspects-Con­ gresses I Maresca, B (Bruno), 1950- II Kobayashi, GeorgeS, 1927- III Yamaguchi, Hldeyo, 1934- IV North Atlantic Treaty OrganizatIOn SCientifiC Affairs DIvIsion V NATO Advanced Research Workshop on Molecular Biology and Its Application to Medical Mycology (1992 Taormina, Italy) VI Series [DNLM 1 Fungl~genetlcs~congresses 2 Molecular Blology-congresses 3 Morphogenesls-congresses 4 Mycology-congresses 5 Yeasts~genetlcs~congresses OW 180 M718 1992] OR245 M645 1993616' 015- dc20 This work IS subject to copYright All rights are reserved, whether the whole or part of the material IS concerned, speCifically the rights of translation, reprinting, reuse of Illustrations, recitation, broadcasting, reproduction on microfilm or In any other way, and storage In data banks DuplicatIOn of this publication or parts thereof IS permitted only under the provIsions of the German CopYright Law of September 9, 1965, In ItS current verSion, and permission for use must always be obtained from Springer-Verlag Violations are liable for prosecution under the German COPYright Law © Springer-Verlag Berlin Heidelberg 1993 Softcover reprint of the hardcover 1 st edition 1993 Typesetting Camera ready by author Book design Donatella Capone, Secretary 11GB Press, Naples, Italy 31/3145 - 5 4 3 2 1 0 - Printed on aCid-free paper Preface With a spectacular view of a grumbling and lava spewing mount Etna in the background, the NATO sponsored workshop "Molecular Biology and its Application to Medical Mycology" provided a stimulatingforumfor a group of researchers who work with fungi pathogenic for humans to interact and discuss problems with molecular biologists who use non-pathogenic fungi primarily as laboratory models for investigation. The workshop was held January 6-8, 1992 in the Congress Center of the San Domenico Palace Hotel, aformer monastery dating back to 1430 located in Taormina, situated high above the coastline of the Mediterranean sea overlooking Isola Bella on the island of Sicily. In this setting the two groups were encouraged to participate in active discussions and exchange of ideas. Thirty invited papers and one poster session were presented in the three day workshop that was divided into six sessions covering: (1) the molecular biology of yeasts; (2) the molecular biology offilamentous fungi; (3) fungal morphogenesis; and (4) the use and application of the newer molecular biology tools in the study of medically importantfungL Eachsession was designed to include studies using pathogenic and non-pathogenic fungi as laboratory models. The opening presentation by Sergio Moreno from Paul Nurse's group at OJiford University set the standardfor theformal presentations. In his paper "Cell cycle regulation in flSsion yeast", he showed that the cdc2+ gene of Schizosaccharomyces pombe encodes a 34kDa phosphoprotein with protein serine/threonine kinase activity. He described current molecular biology studies on its role in mitosis during ceU cycle of this yeast. This talk was followed by Claudina Roudrigues-Pousadafrom Oeiras, Portugal who described her studies on acquisition ofthermo tolerance in Saccharomyces cerevisiae using 1, 1 O-phenantroline an iron chelating compound that induces arrest ofgrowth at "start", during which time they acquire thermotolerance without producing a full set of heat shock proteins. Bridging the gap between studies on non­ pathogenic fungi and pathogens was the paper given by Gerald Fink of the Whitehead Institute in Boston, Massachusetts. He described his thought provoking studies with nutritionally deprived diploid strains ofS. cerevisiae that undergo changes in ceU shape and pattern of cell division that results in filamentous growth. These observations implied some very important implications for animal pathogenesis in that fllamentation in yeasts of the genus Candida is often correlated with the process of pathogenicity. The difficulty of using clasSical genetic technics to investigate yeast belonging to the genus Candida was emphasized by Masamichi Takagifrom the University VI of Tokyo with his strategy of reverse genetics by using recombinant DNA technology. Using technics of molecular cloning, Richard Calderone of Georgetown University School of Medicine described the isolation of a gene fragment from C. albicans which shows homology with human complement receptor (CR2) gene. Closing the.first session was Jacob Reiserfrom the Swiss Federal Institute of Technology of Zurich, Switzerland who described his molecular biological studies with the genus Trichosporon, which include yeast­ like fungi that have been implicated as opportunistic pathogens of humans. The contributions presented in the two sessions onftlamentousfungifocused mainly on studies using Aspergillus nidulans and Neurospora crassa. These studies clearly illustrated the advantages these fungi offer over those that cause disease in man and animals particularly in the area of molecular genetics. Based on advances made in this area, Yuzuru Iimura described his studies on the development ofmolecular genetics systemsfor several industrial species including A. niger and A. oryzae. Studies from Geojfrey Turner's laboratory on expression of genes for the biosynthesis of penicillin further support the contention that rapid basic and molecular biological advances are made when the problem involves an industrially important metabolite particularly when it is produced by a non-pathogen. The exception, however is in the area of phytopathology where Flora Banuett described her elegant studies on Ustilago maydis. Her work and those ofothers who work with plant pathogens clearly point out the deficiencies and paucity of information that exists when it comes to Similar studies on the molecular biology involvingfungi that cause disease of humans and animals. In the second session, molecular biological studies with yeast, it became evident that great inroads are being made in Similar areas with medicaUy importantfungL Several investigators have been motivated to study Candida albicans and Cryptococcus neoformans because ofimportant clinical questions that remain unanswered concerning host-parasite interaction and the paucity of information on its virulence, and pathogenesis. Jim Cutler described his studies on the characterization ofC. albicans-speciftc DNAfragment that may be useful diagnostically. Interest in and studies with C. neoformans are rapidly increasing and a great deal ofprogress has been made in our knowledge ofthe genetics and biochemistry