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SaifHameed· PoojaVijayaraghavanEditors
Recent Advances in Human Fungal Diseases
Progress and Prospects
Recent Advances in Human Fungal Diseases
Saif Hameed • Pooja Vijayaraghavan
Editors
Recent Advances in Human Fungal Diseases
Progress andProspects
Editors
Saif Hameed Amity Institute of Biotechnology Amity University Haryana Gurugram, Haryana, India
Pooja Vijayaraghavan Amity Institute of Biotechnology Amity University Noida, Uttar Pradesh, India
ISBN 978-981-97-4908-9 ISBN 978-981-97-4909-6 (eBook)
https://doi.org/10.1007/978-981-97-4909-6
© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2024 This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher, whether the whole or part of the material is concerned, specically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microlms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specic statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional afliations.
This Springer imprint is published by the registered company Springer Nature Singapore Pte Ltd. The registered company address is: 152 Beach Road, #21-01/04 Gateway East, Singapore 189721, Singapore
If disposing of this product, please recycle the paper.

Foreword

This comprehensive book provides an insightful approach to the current advances in the area of fungal diseases, namely Candidiasis and Aspergillosis. The fungi caus­ing these diseases, namely the yeast genera Candida and lamentous Aspergillus species, are ubiquitously present in the environment and also comprise the human body ora. We are constantly exposed to these fungi that rarely cause infection among normal hosts. However, a change in host immune status to an immunocom­promised one increases the susceptibility to fungal diseases. During the recent COVID pandemic, which impacted the entire world, several immunosuppressed patients were affected with secondary fungal infections. Fungal infections were brought to the forefront, and we were caught on our back foot regarding the com­prehensive treatments and therapies for fungal infections.
There are several features of fungal diseases, including epidemiology, diagnos­tics, pathogenesis, virulence, host–pathogen interaction, drug resistance, and thera­peutic aspects. The knowledge and understanding of these aspects are necessary to understand the management of fungal diseases. This book presents a compilation of articles for updated management of Candidiasis and Aspergillosis. First, the authors have presented a comprehensive approach to the traditional therapeutic strategies and the newly evolving strategies for disease management. Drug resistance of these fungi is a hurdle in treatment due to overexposure to antifungals and the extensive use of antifungals in poultry and dairy farms. The development of effective fungal mechanisms like drug efux to overcome the drug is a challenging aspect. Another unique challenge during the treatment and therapy of fungi is the development of fungal biolms that are multi-structured morphological units displaying drug resis­tance and persistence. These aspects are addressed in adequately in this book. Moreover, the authors have included a section on the host–pathogen interaction to discern the aspects of microbial pathogenicity and design better treatment options and prevent infectious fungal disease.
Another troubling aspect is the increasing incidence of multidrug-resistant fun­gal pathogens. Candida auris is being increasingly reported worldwide for its mul­tidrug resistance. Global tracking and the genomic study of such organisms can help to develop strategies to tackle these incidences. Virulence attributes of the multidrug­resistant organisms can be studied to identify molecular targets and provide assis­tance to the suffering. Similarly, the spectrum of infectious and allergic syndromes related to Aspergillus infections is rather heterogeneous, with incidences of
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Foreword
restricted colonization in immunocompetent hosts. Incidences of allergic broncho­pulmonary aspergillosis, rhinitis, farmer’s lung, localized aspergilloma, and more invasive and disseminated infections are seen in the immunocompromised patients. It is worrying that these diseases are often associated with high mortalities. The range of diseases is disturbing and requires a rational approach to treat and manage such diseases.
Diagnostics can be the rst approach for the correct identication of fungal pathogens to proceed with their timely treatment. Diagnostics of fungal disease depend on traditional methods of culturing in several laboratories and clinics. Proven cases are often conrmed by microbiological identication and presence of clinical symptoms. Evolving early detection techniques can denitely contribute to improved management of fungal disease. The authors have addressed these needs in this volume. This book comprises contributory chapters written by well-respected authors. The information present in this book will be helpful to scientists, research­ers, and medical practitioners and will also serve as a valuable reference text for the university students.
VandanaGhormade
Pune, India

Preface

The book titled Recent Advances in Human Fungal Diseases: Progress and Prospects aims to comprehensively explore various aspects of mycology, with a
specic focus on advancements and ongoing research related to human fungal pathogens. The eld of clinical research on fungal infections is often overlooked, particularly in health care settings in Asian countries and the Indian subcontinent. Invasive fungal infections have a signicant global impact on human health, causing approximately 1.5 million deaths annually, comparable to well-known infectious diseases like tuberculosis or malaria. The primary culprits, Candida and Aspergillus, are responsible for over 75% of human fungal infections.
Candidiasis, characterized by supercial or systemic infections caused by Candida species, can affect various parts of the body, including the skin, intestinal tracts, host tissues, and blood. C. albicans is the predominant cause of both super­cial and systemic candidiasis in humans. Similarly, Aspergillus infections, primarily caused by A. fumigatus acquired from the environment, lead to pulmonary compli­cations such as allergic bronchopulmonary aspergillosis and invasive aspergillosis, particularly in immunocompromised individuals. Mortality rates in vulnerable pop­ulations range from 40% to 90%. The emergence of drug resistance further compli­cates the treatment landscape.
Addressing drug resistance is a signicant challenge for clinicians, given its mul­tifactorial nature with various contributing mechanisms. Recently identied C. auris, the rst fungal pathogen recognized as a public health threat, exhibits intrinsic resistance to antifungals. Hence, there is an urgent social need to compre­hend the epidemiology, diagnostics, drug resistance, and therapeutics of these major human fungal pathogens.
To meet this need, a comprehensive reference book has been compiled to present an up-to-date perspective on mycological research, consolidating recent develop­ments into a state-of-the-art framework. This book focuses on the biology of human fungal infections, specically targeting the most common fungal pathogens—Can- dida and Aspergillus. This book is structured into two sections, “Candida and Candidiasis” and “Aspergillus and Aspergillosis,” each summarizing key themes such as epidemiology, diagnostics, pathogenesis, virulence, host–pathogen interac­tion, drug resistance, and therapeutic aspects.
Contributions from selected experts and renowned veterans in the eld enrich the book with cutting-edge research. It serves as a valuable research-based reference for
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biomedical scientists, researchers, and professionals in the healthcare industry involved in various aspects of human fungal diseases. Additionally, students in the elds of biomedicine, pathology, and pharmacy will nd this book benecial. The editors express their gratitude to the esteemed contributors for their valuable and timely input, acknowledging their pivotal role in making this compilation a ready reference for researchers in the eld.
Gurugram, Haryana, India SaifHameed Noida, Uttar Pradesh, India PoojaVijayaraghavan

Contents

Part I Candida and Candidiasis
1 Diagnostics of Candida and Candidiasis: Current Methods
and Future Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Sukalyani Banik
2 Fungal Fighters: A Comprehensive Guide to Antifungal Therapies
of the Past, Present, and Future . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
Biswambhar Biswas and Anil Thakur
3 Candidiasis Treatment: An Evolutionary Journey from Past
to Present and a Glimpse into the Future . . . . . . . . . . . . . . . . . . . . . . . . 65
Md Nazmul Islam Bappy, Tanjin Barketullah Robin, and Kazi Md. Ali Zinnah
4 MDR in Candida: The Real Storm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
Prashansha Srivastava, Shashikant Tiwari, Manoj Kumar, Manoj V. Murhekar, and Gaurav Raj Dwivedi
5 Surviving the Storm: How Candida Species Master Adaptation
for Pathogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109
Aishwarya Rana, Nidhi Gupta, Shumaiza Asif, and Anil Thakur
6 Molecular Cues and Mechanisms of Pathogenesis in Candida . . . . . . 157
Somnath Sahoo and Kongara Hanumantha Rao
7 Factors Affecting Drug Resistance and Virulence
in Fungal Pathogen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175
Preeti Sharma, Deepika Kumari, Pammi Kumari, Antresh Kumar, and Ritu Pasrija
8 Unravelling Drug Resistance in Candida Species: Genetic,
Biofilm, Transcriptional, and Epigenetic Perspectives . . . . . . . . . . . . . 203
Ajeet Kumar, Ashik Francis, Sandeep Hans, and Anil Thakur
9 Biofilm Formation in Candida Species . . . . . . . . . . . . . . . . . . . . . . . . . . 239
Mba Ifeanyi Elibe and Nweze Emeka Innocent
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Contents
10 Dissemination of Candida auris Biofilms: A Medical Abrosia . . . . . . . 261
Garima Gangwar, Bharti Singh, and Rekha Puria
11 Polymicrobial Biofilms of C. albicans with Bacterial Species:
An Insight into Intergenus Interaction . . . . . . . . . . . . . . . . . . . . . . . . . . 281
Purvi Joshi, Pinal Trivedi, Rohit Bhattacharjee, Muskan Sahu, and Devarshi Gajjar
12 Decoding the Complex Terrain of Candida tropicalis-Induced
Candidiasis: Insights into Epidemiology, Infection Mechanisms,
Therapeutics, and Drug Resistance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 301
Monalika Gupta, Sana Akhtar Usmani, Khushboo Arya, Shikha Chandra, Saumya Chaturvedi, Nitin Bhardwaj, Rajendra Prasad, and Ashutosh Singh
13 Candidiasis, Drug Resistance, and Translational Research . . . . . . . . . 319
Anubhuti Jha and Awanish Kumar
Part II Aspergillus and Aspergillosis
14 Therapeutic Strategies and Challenges in the Management
of Aspergillus Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 335
Deotima Das, Ayan Prasad Mukherjee, Saurabh Kumar Jha, and Rashmi Minocha
15 Aspergillus Therapeutics: Future Agents . . . . . . . . . . . . . . . . . . . . . . . . 365
Yashik Bansal, Reetu Kundu, and Nidhi Singla
16 Recent Advances in the Management of Aspergillosis . . . . . . . . . . . . . . 383
Chhavi Gupta and Sajad Ahmad Dar
17 Drug-Resistance Patterns in Opportunistic Aspergilli:
A Molecular Perspective . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 401
Sonia Kumari Shishodia, Raman Thakur, Priya Gautam, Saurav, Neha, and Jata Shankar
18 A Comprehensive and Intricate Dynamics of Aspergillus:
Implications, Therapeutic Challenges, and Drug Resistance . . . . . . . . 427
Nabajit Kumar Borah, Yukti Tripathi, Aditi Parashar, Seneha Santoshi, and Hina Bansal
19 Understanding Molecular Pathogenesis of Aspergillus fumigatus . . . . 457
Pooja Sen, Lovely Gupta, Aman Singh, Lokesh Kumar, Rajan Kumar Mishra, and Pooja Vijayaraghavan