Fungal Pathogenesis in Humans The Growing Threat Edited by Fernando Leal Printed Edition of the Special Issue Published in Genes www.mdpi.com/journal/genes Fungal Pathogenesis in Humans Fungal Pathogenesis in Humans The Growing Threat Special Issue Editor Fernando Leal MDPI • Basel • Beijing • Wuhan • Barcelona • Belgrade Special Issue Editor Fernando Leal Instituto de Biolog´ıa Funcional y Genomica/Universidad´ de Salamanca Spain Editorial Office MDPI St. Alban-Anlage 66 4052 Basel, Switzerland This is a reprint of articles from the Special Issue published online in the open access journal Genes (ISSN 2073-4425) from 2018 to 2019 (available at: https://www.mdpi.com/journal/genes/special issues/Fungal Pathogenesis Humans Growing Threat). For citation purposes, cite each article independently as indicated on the article page online and as indicated below: LastName, A.A.; LastName, B.B.; LastName, C.C. Article Title. Journal Name Year, Article Number, Page Range. ISBN 978-3-03897-900-5 (Pbk) ISBN 978-3-03897-901-2 (PDF) Cover image courtesy of Fernando Leal. c 2019 by the authors. Articles in this book are Open Access and distributed under the Creative Commons Attribution (CC BY) license, which allows users to download, copy and build upon published articles, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. The book as a whole is distributed by MDPI under the terms and conditions of the Creative Commons license CC BY-NC-ND. Contents About the Special Issue Editor ...................................... vii Fernando Leal Special Issue: Fungal Pathogenesis in Humans: The Growing Threat Reprinted from: Genes 2019, 10, 136, doi:10.3390/genes10020136 ................... 1 Liang Huo, Ping Zhang, Chenxi Li, Kashif Rahim, Xiaoran Hao, Biyun Xiang and Xudong Zhu Genome-Wide Identification of circRNAs in Pathogenic Basidiomycetous Yeast Cryptococcus neoformans Suggests Conserved circRNA Host Genes over Kingdoms Reprinted from: Genes 2018, 9, 118, doi:10.3390/genes9030118 .................... 5 C´elia F. Rodrigues and Mariana Henriques Portrait of Matrix Gene Expression in Candida glabrata Biofilms with Stress Induced by Different Drugs Reprinted from: Genes 2018, 9, 205, doi:10.3390/genes9040205 .................... 18 Roc´ıo Vicentefranqueira, Jorge Amich, Laura Mar´ın, Clara In´es S´anchez, Fernando Leal and Jos´e Antonio Calera The Transcription Factor ZafA Regulates the Homeostatic and Adaptive Response to Zinc Starvation in Aspergillus fumigatus Reprinted from: Genes 2018, 9, 318, doi:10.3390/genes9070318 .................... 34 Mafalda Cavalheiro, Pedro Pais, M´onica Galocha and Miguel C. Teixeira Host-Pathogen Interactions Mediated by MDR Transporters in Fungi: As Pleiotropic as it Gets! Reprinted from: Genes 2018, 9, 332, doi:10.3390/genes9070332 .................... 67 Eta E. Ashu and Jianping Xu Strengthening the One Health Agenda: The Role of Molecular Epidemiology in Aspergillus Threat Management Reprinted from: Genes 2018, 9, 359, doi:10.3390/genes9070359 .................... 96 Monise Fazolin Petrucelli, Kamila Peronni, Pablo Rodrigo Sanches, Tatiana Takahasi Komoto, Josie Budag Matsuda, Wilson Araujo ´ da Silva Junior, Rene Oliveira Beleboni, Nilce Maria Martinez-Rossi, Mozart Marins and Ana Lucia ´ Fachin Dual RNA-Seq Analysis of Trichophyton rubrum and HaCat Keratinocyte Co-Culture Highlights Important Genes for Fungal-Host Interaction Reprinted from: Genes 2018, 9, 362, doi:10.3390/genes9070362 ....................110 Rocio Garcia-Rubio, Sara Monzon, Laura Alcazar-Fuoli, Isabel Cuesta and Emilia Mellado Genome-Wide Comparative Analysis of Aspergillus fumigatus Strains: The Reference Genome as a Matter of Concern Reprinted from: Genes 2018, 9, 363, doi:10.3390/genes9070363 ....................128 Roberta Peres da Silva, Sharon de Toledo Martins, Juliana Rizzo, Flavia C. G. dos Reis, Luna S. Joffe, Marilene Vainstein, Livia Kmetzsch, D´ebora L. Oliveira, Rosana Puccia, Samuel Goldenberg, Marcio L. Rodrigues and Lysangela R. Alves Golgi Reassembly and Stacking Protein (GRASP) Participates in Vesicle-Mediated RNA Export in Cryptococcus neoformans Reprinted from: Genes 2018, 9, 400, doi:10.3390/genes9080400 ....................147 v Ana Carolina Remondi Souza, Beth Burgwyn Fuchs, Viviane de Souza Alves, Elamparithi Jayamani, Arnaldo Lopes Colombo and Eleftherios Mylonakis Pathogenesis of the Candida parapsilosis Complex in the Model Host Caenorhabditis elegans Reprinted from: Genes 2018, 9, 401, doi:10.3390/genes9080401 ....................164 Toni Ciudad, Alberto Bellido, Encarnaci´on Andaluz, Bel´en Hermosa and Germ´an Larriba Role of Homologous Recombination Genes in Repair of Alkylation Base Damage by Candida albicans Reprinted from: Genes 2018, 9, 447, doi:10.3390/genes9090447 ....................175 Pei Pei Chong, Voon Kin Chin, Won Fen Wong, Priya Madhavan, Voon Chen Yong and Chung Yeng Looi Transcriptomic and Genomic Approaches for Unravelling Candida albicans Biofilm Formation and Drug Resistance—An Update Reprinted from: Genes 2018, 9, 540, doi:10.3390/genes9110540 ....................190 Ulrike Binder, Maria Isabel Navarro-Mendoza, Verena Naschberger, Ingo Bauer, Francisco E. Nicolas, Johannes D. Pallua, Cornelia Lass-Fl¨orl and Victoriano Garre Generation of A Mucor circinelloides Reporter Strain—A Promising New Tool to Study Antifungal Drug Efficacy and Mucormycosis Reprinted from: Genes 2018, 9, 613, doi:10.3390/genes9120613 ....................208 vi About the Special Issue Editor Fernando Leal obtained his Bachelor, Master, and Ph.D. degrees in Biology from Salamanca University (Spain). After a postdoctoral training as a Fulbright fellow at the National Cancer Institute (N.I.H., Bethesda, MD, USA) he became a faculty member (Assistant/Associate Professor/Vice Dean) of the Biology School of Salamanca University. At the same time, he became research group leader and vice director at the Institute of Microbial Biochemistry (a joint center of the Spanish Research Council and the University of Salamanca). He is currently a Full Professor at the same University. Dr. Leal has more than 30 years of research experience in different fields, such as yeast’s plasma membrane, viral oncogenes, molecular biology of fungal pathogenesis, and Aspergillus proteomics. During a recent sabbatical stay at Edinburgh University, he was involved in a project dealing with the alteration of miRNAs export in exosomes after Vaccinia virus infection. He has published numerous scientific research papers and has collaborated as a reviewer and editor with several ++ scientific journals. His current research interests focus on the mechanisms of gene regulation by Zn in Aspergillus fumigatus and their role in virulence and pathogenesis. vii G C A T T A C G G C A T genes Editorial Special Issue: Fungal Pathogenesis in Humans: The Growing Threat Fernando Leal Instituto de Biología Funcional y Genómica/Dpto. Microbiología y Genética, (CSIC/USAL), Zacarías González 2, 37007 Salamanca, Spain; fl[email protected] Received: 1 February 2019; Accepted: 4 February 2019; Published: 12 February 2019 Approximately 150 fungal species are considered as primary pathogens of humans and animals. The variety of infections that they may cause ranges from localized cutaneous, subcutaneous or mucosal infections to systemic and potentially fatal diseases. Many fungi are also able to cause lesions when abnormal patient susceptibility exists or after traumatic colonization of the fungus (for a comprehensive review on Medical Mycology, see Kwon-Chung and Bennet, [1]). Fungi that infect immunocompromised patients are referred to as opportunistic pathogens. The number of opportunistic fungi has recently increased due to the arrival of new and growing populations of immunocompromised hosts. In this special issue, we have attempted to compile a collection of new studies investigating the role of some virulence traits and their molecular mechanisms of action in the pathogenic outcome of fungal infections. The term candidiasis refers to a wide clinical spectrum of infections that can be acute or chronic, superficial (cutaneous, oropharyngeal, vulvovaginal, ocular) or deep (esophageal, gastrointestinal, respiratory, urinary, etc.) and can affect either normal or immunosuppressed individuals. The major etiologic agent is Candida albicans, which is part of the normal human mycobiota. However, several other species are frequently encountered in certain clinical diseases (Candida parapsilosis, Candida glabrata, Candida tropicalis, Candida lusitaniae). Here, three different aspects of Candida infections are examined: the maintenance of chromosomal integrity; biofilm formation as a form of survival; and the establishment of new models of infection as an alternative to mice. Ciudad et al. [2] address the problem of repairing the alkylation base damage in the genome of C. albicans. After analyzing the response of three homologous recombination (HR) mutants to chromosomal damage caused by methyl methanesulfonate (MMS), these authors propose that repair takes place through a mechanism (possibly base excision repair) that does not involve homologous recombination. Biofilm formation allows Candida to adhere to and proliferate on medical devices and host tissues. Biofilms are constituted of a mixture of filamentous and yeast cells that surround themselves with an extracellular matrix, which provides a remarkable degree of resistance to antifungal drugs. Rodrigues et al. [3] evaluate the role of C. parapsilosis genes associated