Plenary session 4 Fungal Secondary Metabolism and Pathogenicity
Chairs: Neil Gow & Tamas Papp
Room: Banqueting hall
PS4.1 A host defense peptide mimetic, brilacidin, potentiates caspofungin antifungal activity against human pathogenic fungi
Gustavo Goldman, Brazil, FECMM
Undergraduate in Biology from Universidade Federal do Rio de Janeiro (1983), MSc in Microbiology from Universidade de São Paulo (1988) and PhD in Molecular Biology from Rijksuniversiteit Gent (1994). Experience in fungal genetics more specifically related to the biology of Aspergillus fumigatus and A. nidulans. Postdoctoral fellow (1993-1994), University of Medicine of New Jersey, USA. Currently Professor of Molecular Biology Universidade de São Paulo and Chief Editor of Frontiers in Fungal Biology.
PS4.2 Tracing the origin and evolution of acid mycophenolic acid production and resistance in fungi
Nicolas Papon, France
Nicolas Papon studied biology and biochemistry at the University of Tours (France). After a PhD in plant biology (2000–2003), he was first recruited as lecturer in botanics and mycology at the Faculty of Pharmacy in Paris. In 2008, he then moved as assistant professor in biotechnology at the Faculty of Pharmacy, University of Tours. He finally moved to the University of Angers in 2015 and was appointed Professor in parasitology, medical mycology, and health biotechnologies. He’s currently leader of the Fungal Respiratory Infections (FRI) Research Unit and he’s also the director of the Federative Structure for Research in Health Sciences (ICAT), University Hospital of Angers.
Mycophenolic acid (MPA) is a natural meroterpenoid well documented for inhibiting inosine monophosphate dehydrogenase involved in de novo purine synthesis. Because of this critical metabolic effect in human T and B lymphocytes, MPA is used for decades as an immunosuppressive agent, mostly in the framework of solid organ transplantations. To date, the pharmaceutical supply of MPA is provided by biotechnological production and purification process from batch cultures of the mold Penicillium brevicompactum.
Historically, MPA production was believed to be restricted to a very limited number of Penicillium species, including P. brevicompactum. However, this has been questioned because of the identification in recent years of few xerophilic Aspergillus species that are also able to produce MPA. We were, therefore, particularly interested in deciphering the origin and evolution of MPA biosynthetic pathway throughout the medically and biotechnologically important family of filamentous fungi, the Aspergillaceae, which encompasses both Penicillium and Aspergillus genera.
By exploring the currently available genomic resources in Aspergillaceae, we primarily identified very few species that contain putative partial to complete gene clusters for MPA biosynthesis. In addition, we sequenced a set of xerophilic strains from four Aspergillus species related to the Aspergillus section some of which had been shown to produce MPA. Interestingly, the production of MPA in one of these species was correlated to the presence of a putative MPA biosynthetic cluster that dramatically differs in term of genomic organisation from that of the originally described in P. brevicompactum. None of the three other newly sequenced Aspergillus species is able to produce MPA. Accordingly, further comparative genomic investigations revealed the lack of a functional MPA gene cluster in these species. Overall, our results thus suggest that genetic determinants underlying MPA biosynthesis likely early emerged from a common ancestor of Aspergillaceae. This study also provides insight into a subsequent and progressive loss of this biosynthesis capacity along the evolution of these filamentous fungi with few exceptions.
Meet the expert session
M11 Management of candidemia
Volkan Özenci. Sweden & Maiken Cavling Arendrup, Denmark
Volkan Özenci, Sweden
Volkan Özenci, professor adjunct in Clinical Microbiology, has a research focus on the improvement of the current state of clinical mycology through evaluation of the analytical and clinical performance of new microbiological diagnostic methods, and development of clinical microbiology methods for rapid detection and identification of clinically relevant fungi. His group has led several clinical studies in collaboration with other centers and the industry.
Dr. Özenci is the current president of President of the Nordic Society for Medical Mycology and vice president of the Swedish Society for Clinical Mycology.
Maiken Cavling Arendrup, Denmark
Prof Maiken Cavling Arendrup (MD) is specialist in clinical microbiology. She holds PhD and Dr. Med. Sci degrees. Currently, Dr. Arendrup is Professor at the University Hospital Rigshospitalet in Copenhagen and the Head of the Mycology Unit at Statens Serum Institut, Copenhagen, where she is responsible for the fungal laboratory, which receives 13,000 routine and reference samples per year for culture, susceptibility testing, antigen- and antibody-detection, and PCR as well as for the national surveillance programmes of candidaemia and of azole resistance in Aspergillus. She is responsible for the supervision of several PhD students.
Prof Arendrup was the founder of the Nordic Society of Medical Mycology (NSMM) the president since the formation of the society in 2003 until 2018. She is chair of the EUCAST Antifungal Susceptibility Testing Subcommittee Steering Committee, head of the EUCAST Development Laboratory for fungi. In 2017 she was appointed Fellow of the European Society for Clinical Microbiology and Infectious Diseases and in 2018 honouree member of the NSMM.
Prof Arendrup has authored 280 publications in international journals and as book chapters. She has received two research awards. Her main research interests include the epidemiology, susceptibility, breakpoint development, diagnostics and treatment of fungal infections.
Maiken Cavling Arendrup
M12 Basic science cryptococcus
Guilhem Janbon, France & Tom Harrison, United Kingdom
Biography Guilhem Janbon
Guilhem Janbon leads the unit RNA Biology in Fungal Pathogens at the Institut Pasteur of Paris, France. He is also the director of the Department of Mycology of this institute. The themes of his research projects are focused on the RNA metabolism of Cryptococcus yeasts. More recently, he also developed number of research projects aimed to understand the biology of extracellular Vesicles (EVs) produced by these yeasts and the impact of their content, including RNAs, in virulence.
Biography Tom Harrison
Tom Harrison is Professor of Infectious Diseases and Medicine, Lead for the Centre for Global Health, and Deputy Director of the Institute for Infection and Immunity, at St Georges University of London, Honorary Consultant at St Georges Hospital, London, and Professor of Medical Mycology at the MRC Centre for Medical Mycology at the University of Exeter. He trained in Infectious Diseases in London and Boston, USA, and works on a clinical and laboratory research programme on the prevention and treatment of cryptococcal meningitis with colleagues at St George’s, the London and Liverpool Schools of Tropical Medicine and across sites in Sub-Saharan Africa. The programme includes studies of pathogen virulence and drug resistance, host immunity, and the development and delivery of phase II and major phase III trials, health economic analyses, and implementation.
Abstract Guilhem Janbon
Extracellular vesicle production and antifungal resistance in Cryptococcus neoformans
Resistance to fluconazole, the most commonly used antifungal, can be associated with a mutation in its target (Erg11) sequence or with a modification of its gene coding and/or drug efflux pump expression. Recent findings have suggested a connection between vesicular trafficking and antifungal resistance. In this study, we discovered new regulators of extracellular vesicle (EV) biogenesis in Cryptococcus neoformans that affect fluconazole resistance. Specifically, the transcription factor Hap2 does not influence the expression of the drug target or efflux pumps, but it does affect the cellular sterol profile. Additionally, the production of EVs is decreased by subinhibitory fluconazole concentrations. Spontaneously fluconazole-resistant colonies generated in vitro displayed altered EV production, and the acquisition of fluconazole resistance was linked to reduced EV production in clinical isolates. Finally, the reversal of fluconazole resistance was associated with an increase in EV production. Therefore, these findings suggest a model in which fungal cells can regulate EV production instead of regulating the expression of the drug target gene as an initial defense against antifungal attack in this fungal pathogen.
Abstract Tom Harrison
Immune responses to cryptococcal infection, and implications for adjunctive immunotherapies.
In vitro, animal model, and human data have all contributed to an increased understanding of the range and complexity of immune responses to cryptococcal infection, and how these responses differ between different at risk patient groups. Characterization of rare genetic defects underlying some cases of cryptococcal disease, and cases associated with the expanding range of biological agents used to treat cancer and autoimmune disorders provide additional evidence for the importance of particular immune pathways in defence against cryptococcosis. While major advances have been made in the optimization of antifungal therapy for cryptococosis, available antifungal drugs are limited and mortality remains high, providing a strong rationale for the development of adjunctive immunomodulatory therapies that target the immune defects underlying most cases of cryptococcosis. Such therapies will be critically dependent on specific host immune status at the time of treatment, will likely be diametrically different in different patient groups, and would be enabled by the development of rapid immuno-diagnostic tests.
M13 Vaginal candidiasis / Oral candidiasis
Esther Segal, Israel, FECMM & Ourania Nicolatou-Galitis, Greece
Biography Ourania Nicolatou-Galitis
Professor Dr Ourania Nicolatou-Galitis, Oral Medicine Oral Oncologist, is a graduate of the National and Kapodistrian University of Athens, and has studied Oral Pathology at Temple University, USA.
She was the main investigator in several international programs and has published manuscripts on oral candidiasis in HIV/AIDS and Cancer patients. She was founding member of the Hellenic Medical Mycology Society. She has received international awards for her studies. Recently, she published on the Oral Toxicities in cancer patients, who received immunotherapy. Oral candidiasis was diagnosed and reported, for the first time, in 6 of 24 patients of the series, https://www.mdpi.com/2673-6373/3/1/11/review_report
Dr Nicolatou-Galitis has served as Chair of the Bone and Musculoskeletal Study Group, Multinational Association of Supportive Care in Cancer-MASCC, 2015-2020, and President of the International Society of Oral Oncology, www.mascc.org
She is Founding Member and Scientific Responsible of the innovative digital platform CureCancer.gr, collaborating with several Oncology Hospitals in Athens, within the EIT Health Program SymbIASIS.
She is also responsible of the educational program “oral Mucositis in cancer” of the British Medical Journal Best Practice, https://bestpractice.bmj.com/ and of the program osteonecrosis of the jaw in cancer patients, who receive Bone targeting Agents” of ecancer.org.
Biography Esther Segal
Prof. Esther Segal (Ph. D) is a Professor of Medical Mycology at the department of Clinical Microbiology and Immunology, School of Medicine, Tel Aviv University, Israel.
Prof. Segal is a graduate of Tel Aviv University, Israel – M. Sc. in Microbiology, and of the University of Bern, Switzerland – Ph. D in yeast genetics. Specializations in Medical Mycology at the CDC in Atlanta, USA, NIH in Bethesda, USA and Institute Pasteur, Paris, France.
Prof. Segal is the President of the Israel Society of Medical Mycology and an ECMM Board member. She was active at the ISHAM Council and acted as ISHAM Vice President.
Prof. Segal’s main research topics were concentrated on pathogenic yeasts, specifically on Candida, focusing on pathogenesis, vaccines and experimental antifungal drugs.
Currently, Prof. Segal is involved in environmental aspects in Marine ecosystems and profiling of antifungal activity of the fungal flora in these ecosystems.
Prof. Segal authored ~ 240 research articles, reviews, book -chapters and coedited (with G. Baum) a book on Pathogenic Yeasts and Yeast Infections (focusing on Candida and Cryptococcus).
Abstract Esther Segal
This presentation has two parts:
1. The first part will cover the current data regarding vaginal candidiasis with focus on epidemiological aspects, diagnosis and treatment, as represented in current published literature. Specific attention is given to the problem of recurrent vaginal candidiasis, its pathogenesis and development of new antifungal drugs for treatment.
2. The second part of the presentation will concentrate on the speaker’s studies. The studies focused on epidemiological aspects, in vitro experiments and on experimental in vivo models. Specifically, the models explored various aspects of Candida attachment to vaginal mucosa, its role in the pathogenesis of the infection and attempts to inhibit this step as a preventive tool
M14 Prophylaxis in a world of increasing antifungal resistance
Neil Clancy, United States
M15 Fungal infections in primary immunodeficiencies
Adilia Warris, United Kingdom, FECMM & Fanny Lanternier, France, FECMM
Infectious diseases Professor, Hopital Necker
Head of French National Reference Center for Invasive Mycoses and Antifungals, Institut Pasteur, Universite Paris Cite
Professor Adilia Warris is a paediatric infectious diseases specialist with a specific interest in medical mycology. She is co-director of the MRC Centre for Medical Mycology at the University of Exeter. She holds an honorary position in paediatric infectious diseases at the Great Ormond Street Hospital in London. Her research profile has a strong translational focus and specific areas of interest include antifungal resistance and host-fungus interactions in specific patient populations. She chairs the European Paediatric Mycology Network (EPMyN) and leads the Fungal Infection Working Group of PENTA Child Health Research. She is Editor-in-Chief of Medical Mycology Case Reports, and has published over 200 peer-reviewed papers and contributed to several book chapters both nationally and internationally. She is actively involved in the development of various international guidelines (ECIL, ESCMID-ECMM) and Consensus Definitions (EORTC) targeted at the diagnosis and management of invasive fungal infections in neonates and children.
Plenary session 5 Antifungal resistance and stewardship
Chairs: Suzana Hadina & t.b.c.
Room: Banqueting hall
PS5.1 The role of stewardship in the fight of fungal resistance
Theoklis Zaoutis, Greece
PS5.2 Fluconazole resistance in Candida parapsilosis: a burning issue
Jesus Guinea Ortega, Spain
Jesús Guinea works as a clinical microbiologist and leads the Molecular Mycology area in the Clinical Microbiology and Infectious Diseases Department at Gregorio Marañón Hospital (Madrid, Spain). He has been conducting research on medical mycology with emphasis in the application of molecular biology to the study of invasive fungal infections, the improved diagnosis of mycoses, and the study of antifungal susceptibility of agents causing mycoses.
He obtained his degree in Pharmacy (1996), completed his training in Microbiology and Parasitology (2002) and got his PhD (2005) later on. He has received several contracts for research from Fondo de Investigación Sanitaria (Instituto de Salud Carlos III, Spanish Ministry of Health) such as Río Hortega and Miguel Servet programs. He received the Young Investigator Award of the European Society of Infectious Diseases and Clinical Microbiology (ESCMID) in 2010. He has been acting as Scientific Secretary of the Steering Committee of the Antifungal Susceptibility Testing Subcommittee of EUCAST (European Committee on Antimicrobial Susceptibility Testing) since 2016.
J. Guinea is co-author of 210 publications in scientific journals (159 in the first quartile and 86 out of them in the first decil), with an accumulated impact factor of 1,787 points and Hirsch index of 40. His scientific production has received 7070 total cites (6,610 without auto-citation) with a mean of 34.3 cites per item. He has participated in multiple national and international multicenter studies and clinical practice guidelines. He has directed three doctoral theses and three more currently undergoing. He has participated in and coordinated several national and international multicentre studies and clinical practice guidelines.
J. Guinea is member of the American Society for Microbiology (ASM) and the European Society for Clinical Microbiology and Infectious Diseases (ESCMID). He has acted as speaker and/or chairman in international meetings such as ICAAC, Microbe, ECCMID and TIMM. He has been editor of Mycopathologia and Journal of Global Antimicrobial Resistance and he is has acted as a reviewer of scientific papers for multiple journals. He has directed three doctoral theses and three more currently undergoing.
For detailed information about his scientific production:
Jesus Guinea Ortega
Room: Banqueting hall