Mycobacterium : Molecular Infection Biology, Pathogenesis, Diagnostics and New Interventions Seyed Ehtesham Hasnain • Nasreen Z. Ehtesham • Sonam Grover Editors

Mycobacterium tuberculosis: Molecular Infection Biology, Pathogenesis, Diagnostics and New Interventions Editors Seyed Ehtesham Hasnain Nasreen Z. Ehtesham JH Institute of Molecular Medicine, Inflammation Biology and Jamia Hamdard Laboratory New , Delhi, ICMR-National Institute of Pathology, Safdarjung Hospital Campus Dr Reddy’s Institute of Life Sciences , Delhi, India University of Campus Hyderabad, India

Sonam Grover JH Institute of Molecular Medicine, Jamia Hamdard New Delhi, Delhi, India

ISBN 978-981-32-9412-7 ISBN 978-981-32-9413-4 (eBook) https://doi.org/10.1007/978-981-32-9413-4

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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 Foreword

I am delighted to write the foreword for Mycobacterium tuberculosis: Molecular Infection Biology, Pathogenesis, Diagnostics and New Interventions, edited by Prof. Seyed Hasnain and colleagues. Prof. Hasnain has brought together an impressive set of experts and authors to contribute to this seminal work. Tuberculosis (TB) remains the leading infectious killer disease of our times, with ten million new cases every year. A large portion of the burden is borne by countries in Asia and sub-Saharan Africa. Recent years have also seen growing numbers of drug and multidrug-resistant TB, leading to higher mortality and morbidity. While TB has been documented in Egyptian mummies, it has learnt to adapt and survive with mankind and continues to pose significant challenges for its control. The major risk factors include those associated with poverty like undernutrition, overcrowding, tobacco and alcohol use, low awareness, and lack of access to quality healthcare services. While HIV infection has been a major driver of TB in sub-Saharan Africa, the growing burden of diabetes and medication-induced are significant risk factors elsewhere. While the End TB targets of the WHO as well as the SDG global targets envision an end to this global epidemic, many gaps in understanding its pathogenesis, transmission, and factors that enhance or reduce the risk of virulence or the devel- opment of resistance mutations remain. Furthermore, there is presently no rapid diagnostic test that can diagnose all forms of TB simply and affordably, and as a consequence, millions of patients face delayed or wrong diagnoses. While a few new drugs have been developed in the last few years, patients with TB still face months or years of treatment with drugs, which could have potentially severe side effects, especially in the case of MDRTB treatment. Attempts have also been made to develop a vaccine that would be more effective than BCG, but the lack of surrogate markers of protection makes clinical trials of new vaccines time-consuming and expensive. This book addresses fundamental biology of tuberculosis as well as non-tubercu- lous mycobacteria, an increasingly recognized cause of chronic lung disease in many parts of the world. I am sure that this book will serve as a comprehensive knowledge base for M. tb, the pathogen that causes TB, as well as non-tuberculous mycobacteria (NTM). It highlights developments in understanding the disease at the molecular level, identification and validation of molecular drug targets, molecular

v vi Foreword epidemiology, and novel diagnostics. A special chapter on TB vaccines describing present and future perspectives is also one of the highlights of this book. Posttrans- lational and epigenetic modifications in Mycobacterium with emphasis on methyltransferases are another key chapter. Functional biology of the unique group of proteins called PE/PPE, present exclusively in the genus Mycobacterium and nowhere else in the living kingdom, is also discussed in the book. The book has a total of 25 chapters written by eminent scientists drawn from abroad and India, such as from Robert Koch Institute, Berlin; Trinity College, Dublin; Harvard T.H. Chan School of Public Health, Boston, MA, USA; Yale School of Medicine, New Haven, USA; Emory University, Atlanta, USA; John Hopkins University, Baltimore, USA; Max Planck Institute for Infection Biology, Berlin, Germany; Indian Institute of Technology, Delhi; Indian Institute of Science, Bangalore; All India Institute of Medical Sciences (AIIMS), Delhi; National Institute of Pathology, New Delhi; National Institute of , New Delhi; ; University of Hyderabad; Jamia Hamdard; etc. A blend of basic scientists, drug discovery researchers, epidemiologists, clinicians, and vaccinologists has collectively focused on various facets of the disease and the causal organisms. With state-of-the-art contributions from experts in the respective domains, I am sure that this volume will be an informative resource for current practitioners as well as students and researchers.

Chief Scientist, WHO Soumya Swaminathan, MD Geneva, Switzerland Preface

Tuberculosis (TB), the disease, and Mycobacterium tuberculosis (M.tb), the causa- tive pathogen, need no introduction. This book on TB will serve as a comprehensive knowledge base for M.tb, as well as nontubercular bacteria (NTM). Presenting a wealth of information on the molecular infection biology of M.tb,as well as nontuberculous mycobacteria (NTM), this book provides an overview of the functional role of the PE/PPE group of proteins, which is exclusive to the genus Mycobacterium, of host-pathogen interactions, and of virulence. It also explores the pathogenesis of the infection, pathology, epidemiology, and diagnosis of NTM. Last but not least, it discusses current and novel approaches in vaccine development against tuberculosis, including the role of nanotechnology. This book highlights developments in understanding the disease at the molecular levels and identification and validation of molecular drug targets, molecular epidemiology, and novel diagnostic techniques. With state-of-the-art contributions from experts in the respective domains, this volume will be an informative resource for current practitioners as well as medical students, postgraduates, and researchers and is expected to be much in demand. The book is mainly divided into three sections covering all major aspects of TB.

Pathogenesis and Epidemiology of Tuberculosis

This section starts with a chapter on the history of tuberculosis with a description of fascinating events starting from the discovery of the elusive TB bacteria. A chapter on TB comorbidities describes the explicit involvement of TB in promoting other lung diseases such as bronchiectasis and chronic obstructive pulmonary disease during childhood. To reduce the global burden of chronic lung diseases, the management of TB in the early stages is imperative. A chapter on the role of host factors in susceptibility to TB serves as a primer to understand the efforts mounted by the host which can be useful in designing host-directed therapies and also reduce tissue damage due to chronic TB infections. A chapter on extrapulmonary tuber- culosis (EPTB) provides an in-depth overview of the clinical diagnosis and treatment of the different forms of EPTB. This section also covers nontubercular mycobacteria (NTM), a high priority due to its misdiagnosis and association with cystic fibrosis, COPD, and nosocomial infections. The last chapter in this section discusses the spread of M.tb strains circulating in New Zealand and emphasizes the need for early vii viii Preface detection and treatment of active cases together with contact tracing, if one has to minimize the emergence of epidemiological clusters of the disease. This chapter also illustrates the importance of a political will and decisive legislation in bringing down the incidence of disease from 150 cases per 100,000 to less than 10 cases per 100,000 and steps a country need to take to avoid new cases of TB.

Molecular and Infection Biology of M.tb

M.tb is highly adapted for survival in the extremely hostile intracellular environment in host . In order to cope up with stresses encountered by the bacterium in macrophages, it modulates its gene expression in various ways. This section is a combination of chapters where molecular aspects of M.tb have been highlighted to understand bacterial survival strategy. This section begins with a chapter on methyltransferases, present in large number in M.tb, modifying DNA, RNA, proteins, lipids, and other biomolecules of both pathogen and host and illustrates how these epigenetic modifiers impact virulence and pathogenesis of M.tb. Three consecutive chapters provide a comprehensive overview on functional biology of the unique group of proteins called PE/PPE, which is present exclusively in the genus Mycobacterium and nowhere else in the living kingdom. The discussions include evolutionary developments, characterization, and transcriptional regulation of the PE/PPE family along with their involvement in host immunomodulation and also showcase the functional role of intrinsically disordered regions concentrated within this protein family. A chapter on the importance of cell wall-associated poly-α-L- glutamine in the biology of pathogenic mycobacteria is also presented in this book which dissects the unique cell wall architecture of M.tb contributing to the unre- stricted success of the bacterium during infection. Cellular stress responses during M.tb infection have been highlighted in the next chapter including the strategies adopted by M.tb to influence the host innate and adaptive immune responses. The role of heat shock proteins in the mycobacterial pathogenesis has also been discussed in a separate chapter. The importance of endoplasmic reticulum (ER) stress in M.tb. pathogenesis including the ER stress pathways evoked by M.tb proteins such as ESAT-6, HBHA, 38-kDa antigen, and PE_PGRS5 is nicely presented in the next chapter. This is followed by a discussion on the role of toxin-antitoxin (TA) systems in bacterial pathogenesis and the abundance of such TA systems in M.tb, which in turn helps the pathogen fight against various cellular stresses including acidic, hypoxic, and oxidative and also challenges posed by the . A detailed description of the nucleotide excision repair (NER) pathway in mycobacteria is in a separate chapter where in-depth studies of the structure-function relationship of DNA repair throw light on the molecular mechanisms employed by M.tb for self- defense. Such studies will enable the development of novel therapeutic interventions against TB. Preface ix

The chapter on mesenchymal stem cells (MSC) describes its potential in M.tb persistence, resuscitation, and disease reactivation and highlights studies on MSCs as a reservoir of M.tb, which could be a probable target for developing new therapeutics against non-replicating bacteria and viable but non-culturable bacteria. The last chapter in this section emphasizes biofilm and its importance in drug resistance and how biofilm disruption could be an important strategy not only to contain the TB bacteria but also to reduce IC50 of antitubercular drugs.

Vaccines, Diagnostics, and New Interventions

This section begins with a detailed description of the best practices for mycobacteria research laboratories, given the deadly nature of this airborne pathogen. It also covers the occupational risks of working with M.tb and identifies the primary and secondary barriers to M.tb exposure, controls that reduce the risk of exposure and also the good practices and guidelines to be followed during experimental manipu- lation so as to avoid getting infected with the bacterium. Of particular interest are the deployment of biosafety cabinets, good waste management practices, spills manage- ment, and of course occupational health programs and facility decontamination. This is followed by comprehensive review on TB vaccines. The presently used whole cell vaccine such as BCG is inefficient in TB-endemic population. Thus, there is an urgent need for novel vaccines capable of providing complete protection in all age groups as well as in different stages of infection. This is followed by a chapter describing the immunotherapeutic properties of Mycobacterium indicus pranii (MIP) and its likely use as an alternative vaccine candidate. MIP, a nonpathogenic saprophytic mycobacterium, shares many cross-reactive antigens with M.tb and proved to be effective in category II TB as an adjunct to MDT. History as well as present status of TB diagnostics has also been covered in a chapter entitled “TB Diagnostics: Journey from Smear Microscopy to Whole Genome Sequencing.” Developing point of care diagnostic with fast, reliable, and affordable features is vital to curb and control TB and HIV-TB burden in resource- poor countries. This is discussed in the chapter that also focusses on the journey of such diagnostic techniques starting from older strategies such as smear microscopy to modern-day techniques like whole genome sequencing. An interesting chapter describes how to break the transmission of TB by bridging the gap in controlling TB in endemic settings. In order to control the spread of MDR-TB, there is a need to use better diagnostic tool and health measures to interrupt pathogen transmission. Challenges and advances in TB drug discovery are also discussed in detail including the advancement of methodologies for enhanc- ing bioavailability of drugs by different means such as nanoparticle-/liposome- mediated delivery systems and devices for sustained release. The last chapter in this section is based on the experience of actual drug discovery gained by the researchers at Johns Hopkins University. While describing the pro- cesses involved in TB drug discovery, and a review of existing candidate drugs, the authors illustrate their efforts in using drug repurposing strategy for development of x Preface new drugs against MDR and XDR strains of M.tb. The very powerful carbapenem antibiotic, belonging to the beta-lactam group, has been used as a model new drug. In addition, the use of antisense RNA-based therapeutics and CRISPER-CAS system- based new interventions are also discussed.

New Delhi, Delhi, India Seyed Ehtesham Hasnain Nasreen Z. Ehtesham Sonam Grover Acknowledgments

This book is made possible, thanks to the unqualified support, hard work and adherence to the deadlines by scientists, clinicians, and academicians from around the globe who took their time off from their other responsibilities to present new knowledge about TB, a disease that largely affects the underprivileged in underde- veloped countries. We are indeed honored to be associated with renowned personalities, working on different aspects of TB, and are humbled by their commit- ment, kindness, and endurance. We do hope that this book will add new knowledge about the unique attributes of this super smart bacteria so as to enable the development of new interventions including drugs and vaccines and also point-of-care, rapid, and cost-effective diag- nosis of TB. The contributions of our reviewers who generously donated their time to review every chapter are gratefully acknowledged. We would like to put on record the efforts of Dr. Soumya Swaminathan, former Director General, Indian Council of Medical Research and Secretary, Department of Health Research, presently Chief Scientist, WHO Geneva, for writing the foreword which elegantly and succinctly summarizes the salient features of the mammoth effort that have gone into compiling this book. We would like to duly acknowledge the editorial support provided by Ms. Ruby Palta (PS to SEH) and Dr. Salma Jamal and Dr. Rishabh Gangwar, Postdocs in our lab for their technical help. Springer Nature deserves full credit for their persistence, professionalism, and enthusiasm during the publication of the book. Finally, our respective families deserve all the credit for allowing us to bypass family and social commitments during the completion of this project.

xi Contents

Part I Pathogenesis and Epidemiology of Tuberculosis 1 History of TB: Robert Koch and Beyond ...... 3 Ashfaq Hasan 2 Tuberculosis as an Underlying Etiological Factor for Other Human Respiratory Diseases ...... 17 Ronan F. O’Toole 3 Host Factors in Tuberculosis ...... 27 Ruxana T. Sadikot 4 Extrapulmonary Tuberculosis ...... 37 Surendra K. Sharma and Alladi Mohan 5 Infections with Nontuberculous Mycobacteria: Increased Awareness and Recent Developments ...... 55 Astrid Lewin and Hubert Schäfer 6 Tuberculosis in New Zealand: Historical Overview to Modern Epidemiology ...... 87 Ronan F. O’Toole

Part II Molecular and Infection Biology of M. tuberculosis 7 Mycobacterial Methyltransferases: Significance in Pathogenesis and Virulence ...... 103 Sonam Grover, Rishabh Gangwar, Salma Jamal, Sabeeha Ali, Khairun Nisaa, Nasreen Z. Ehtesham, and Seyed Ehtesham Hasnain 8 The PE and PPE Family Proteins of Mycobacterium tuberculosis: What they Are Up To? ...... 123 Ravi Pal, Faiza Nazar, and Sangita Mukhopadhyay 9 Intrinsically Disordered Regions in PE/PPE Protein Family of Mycobacterium tuberculosis: Moonlighting Function ...... 151 Farha Naz, Javeed Ahmad, Mohd Shariq, Mohd Arish, Javaid A. Sheikh, Seyed E. Hasnain, and Nasreen Z. Ehtesham

xiii xiv Contents

10 Comparative In Silico Analyses Reveal Crucial Factors for Virulence, Antigenicity, and Evolution in M.tb ...... 171 Yadvir Singh 11 Importance of Cell Wall-Associated Poly-α-L-Glutamine in the Biology of Pathogenic Mycobacteria ...... 189 Rajni Garg, Rajesh Mani, Manish Gupta, Deeksha Tripathi, Harish Chandra, Rakesh Bhatnagar, and Nirupama Banerjee 12 Cellular Stress Responses and Immunological Regulations During Mycobacterium tuberculosis Infection ...... 203 Nooruddin Khan, Gillipsie Minhas, K. Kala jyothi, and Jyoti Sharma 13 Heat Shock Proteins in the Pathogenesis of Mycobacterium tuberculosis ...... 221 Prajna Tripathi and Janendra K. Batra 14 Endoplasmic Reticulum Stress: Importance in Pathogenesis of Mycobacterium tuberculosis ...... 241 Tarina Sharma, Sonam Grover, Nasreen Z. Ehtesham, and Seyed E. Hasnain 15 Toxin-Antitoxin (TA) Systems in Stress Survival and Pathogenesis ...... 257 Ashutosh Kumar, Anwar Alam, Pranami Bharadwaj, Sharmistha Tapadar, Mamta Rani, and Seyed E. Hasnain 16 Nucleotide Excision Repair Pathway in Mycobacteria ...... 275 Manoj Thakur and K. Muniyappa 17 Mesenchymal Stem Cells: A Hidden Arsenal for Mtb Persistence, Resuscitation, and Reactivation ...... 301 Jaishree Garhyan, Bikul Das, and Rakesh Bhatnagar 18 Biofilms: A Phenotypic Mechanism of Bacteria Conferring Tolerance Against Stress and Antibiotics ...... 315 Anwar Alam, Ashutosh Kumar, Prajna Tripathi, Nasreen Z. Ehtesham, and Seyed E. Hasnain

Part III Vaccines, Diagnostics and New Interventions 19 Best Practices in Mycobacterial Research Laboratories ...... 337 Noman Siddiqi 20 Clinical Aspects and Principles of Management of Tuberculosis ...... 355 Ashfaq Hasan, Sai Haranath Praveen, Chandrakant Tarke, and Fahad Abdullah Contents xv

21 Tuberculosis Vaccine: Past Experiences and Future Prospects .... 375 Gurpreet Kaur, Deepjyoti K. Das, Sanpreet Singh, Junaid Khan, Mohammad Sajid, Hilal Bashir, Mohammad Aqdas, Shikha Negi, Uthaman Gowthaman, and Javed N. Agrewala 22 Immunotherapeutic Potential of Mycobacterium indicus pranii Against Tuberculosis ...... 407 Sangeeta Bhaskar and Bindu Singh 23 TB Diagnostics: Journey from Smear Microscopy to Whole Genome Sequencing ...... 419 Himanshu Vashistha and K. K. Chopra 24 Breaking the Transmission of TB: A Roadmap to Bridge the Gaps in Controlling TB in Endemic Settings ...... 451 Pooja Singh, Jasmine Samal, Sheeba Zarin, Ravikrishnan Elangovan, Seyed E. Hasnain, and Nasreen Z. Ehtesham 25 Challenges and Advances in TB Drug Discovery ...... 463 Garima Khare, Prachi Nangpal, and Anil K. Tyagi 26 Repurposing of Carbapenems for the Treatment of Drug-Resistant Tuberculosis ...... 497 Pankaj Kumar, Urvashi B. Singh, Gyanu Lamichhane, and Elizabeth Story-Roller About the Editors

Prof. Seyed Ehtesham Hasnain has contributed significantly to tuberculo- sis (TB) research, focusing on infection biology and functional epidemiology. He is Fellow of Robert Koch Institute (Berlin), American Academy of Microbiology (USA), TWAS, and all major Indian Science Academies (FNA/FASc/FNASc) and member of German National Academy of Sciences Leopoldina. He has received numerous recognitions and honors, including Alexander von Humboldt Research Award (Germany), Shanti Swarup Bhatnagar Prize, GD Birla Award, JC Bose Fellowship Award, and many others. A former member of the Science Advisory Council to the Prime Minister of India for two terms (2004–2014), he was the firstdirectorofthe Centre for DNA Fingerprinting and Diagnostics, Hyderabad, and later vice-chancellor of the prestigious University of Hyderabad (2005–2011) and served as invited profes- sor at the IIT Delhi (2011–2019). Currently, he is the Vice-Chancellor of Jamia Hamdard and also professor at JH Institute of Molecular Medicine, where he leads a very large, active, and generously funded TB research group.

Dr. Nasreen Z. Ehtesham received her Master’s degree from Aligarh Muslim University, Aligarh, and graduate training from the University of Alberta, Edmonton, Canada. She pursued her Ph.D. at the National Institute of Immunology, New Delhi (1991), and joined the ICGEB as a Rockefeller postdoc fellow. She was appointed as Deputy Director, National Institute of Nutrition, Hyderabad, where her group focused on nutrition and inflammation biology. She established the link between pathogenesis, inflammation, and stress response using the Mycobacterium tuberculosis infection model. An elected Fellow of the National Academy of Sciences, she has served as a member of several decision-making bodies of the Health and S&T ministries. She is the recipient of many awards, including the ICMR Kshanika Oration Award for her contributions to tuberculosis biology. She has published over 70 research papers in prestigious journals such as PNAS and serves on the editorial boards of a number of journals. Currently, she is Director-in-Charge of the ICMR National Institute of Pathology, New Delhi.

Dr. Sonam Grover is a UGC Assistant Professor at JH Institute of Molecular Medicine, Jamia Hamdard, New Delhi. She completed her Ph.D. at JNU (2014) and joined Kusuma School of Biological Sciences, IIT Delhi, as a postdoctoral

xvii xviii About the Editors fellow in the same year. During this tenure, she received a Women Scientist Grant from the Department of Health Research, . Her main areas of research include Mycobacterium tuberculosis host-pathogen interactions, drug repurposing, and identifying novel drug targets against tuberculosis. She has published over 25 research papers in various international peer-reviewed journals including mBio and Molecular Neurobiology. She has delivered talks and presented her work at several national and international conferences and symposia. She is PI/ co-PI in research projects funded by agencies such as DBT and DHR. She was also awarded the prestigious “ASCB Travel Award for Graduate Students” for presenting her research at international conferences. Contributors

Fahad Abdullah Department of Respiratory Medicine, Deccan College of Medical Sciences, Hyderabad, India Javed N. Agrewala Immunology Laboratory, Institute of Microbial Technology, Chandigarh, India Centre for Biomedical Engineering, Indian Institute of Technology-Ropar, Rupnagar, India Javeed Ahmad Inflammation Biology and Cell Signaling Laboratory, ICMR-National Institute of Pathology, Safdarjung Hospital Campus, New Delhi, Delhi, India Anwar Alam JH Institute of Molecular Medicine, Jamia Hamdard, New Delhi, Delhi, India Inflammation Biology and Cell Signaling Laboratory, ICMR-National Institute of Pathology, Safdarjung Hospital Campus, New Delhi, Delhi, India Mohammad Aqdas Immunology Laboratory, Institute of Microbial Technology, Chandigarh, India Mohd Arish JH Institute of Molecular Medicine, Jamia Hamdard, New Delhi, Delhi, India Nirupama Banerjee Molecular Biology and Genetic Engineering Laboratory, School of Biotechnology, Jawaharlal Nehru University, New Delhi, Delhi, India Hilal Bashir Immunology Laboratory, Institute of Microbial Technology, Chandigarh, India Janendra K. Batra National Institute of Immunology, New Delhi, Delhi, India Department of Biochemistry, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, Delhi, India Pranami Bharadwaj Department of Microbiology, Tripura University (A Central University), Agartala, Tripura, India Sangeeta Bhaskar Product Development Cell-I, National Institute of Immunology, New Delhi, Delhi, India

xix xx Contributors

Rakesh Bhatnagar Molecular Biology and Genetic Engineering Laboratory, School of Biotechnology, Jawaharlal Nehru University, New Delhi, Delhi, India Banaras Hindu University, Varanasi, Uttar Pradesh, India Harish Chandra Department of Microbiology, School of Biomedical & Pharma- ceutical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow, India K. K. Chopra New Delhi Tuberculosis Center, New Delhi, Delhi, India Bikul Das Department of Stem Cell and Infectious Diseases, Kavikrishna Labora- tory, Guwahati Biotech Park, Indian Institute of Technology, Guwahati, India Department of Stem Cells and Infectious Diseases, Thoreau Laboratory for Global Health, M2D2, University of Massachusetts, Lowell, MA, USA Deepjyoti K. Das Immunology Laboratory, Institute of Microbial Technology, Chandigarh, India Nasreen Z. Ehtesham Inflammation Biology and Cell Signaling Laboratory, ICMR-National Institute of Pathology, Safdarjung Hospital Campus, New Delhi, Delhi, India Ravikrishnan Elangovan Department of Biochemical Engineering and Biotech- nology, Indian Institute of Technology-Delhi, New Delhi, Delhi, India Rishabh Gangwar JH Institute of Molecular Medicine, Jamia Hamdard, New Delhi, Delhi, India Rajni Garg Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, Karnataka, India Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, Karnataka, India Jaishree Garhyan Department of Microbiology, University of Massachusetts, Amherst, MA, USA Molecular Biology and Genetic Engineering Laboratory, School of Biotechnology, Jawaharlal Nehru University, New Delhi, Delhi, India Uthaman Gowthaman Department of Laboratory Medicine, Immunobiology and Orthopedics, Yale University School of Medicine, New Haven, CT, USA Sonam Grover JH Institute of Molecular Medicine, Jamia Hamdard, New Delhi, Delhi, India Manish Gupta Molecular Biology and Genetic Engineering Laboratory, School of Biotechnology, Jawaharlal Nehru University, New Delhi, Delhi, India Ashfaq Hasan Department of Respiratory Medicine, Deccan College of Medical Sciences, Hyderabad, India Contributors xxi

Seyed Ehtesham Hasnain JH Institute of Molecular Medicine, Jamia Hamdard, New Delhi, Delhi, India Dr Reddy’s Institute of Life Sciences, University of Hyderabad Campus, Hyderabad, India Salma Jamal JH Institute of Molecular Medicine, Jamia Hamdard, New Delhi, Delhi, India K. Kala jyothi Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana, India Gurpreet Kaur Immunology Laboratory, Institute of Microbial Technology, Chandigarh, India Centre for Biomedical Engineering, Indian Institute of Technology-Ropar, Rupnagar, India Junaid Khan Immunology Laboratory, Institute of Microbial Technology, Chandigarh, India Nooruddin Khan Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana, India Garima Khare Department of Biochemistry, University of Delhi South Campus, New Delhi, Delhi, India Ashutosh Kumar Department of Microbiology, Tripura University (A Central University), Agartala, Tripura, India Pankaj Kumar Department of Biochemistry, School of Chemical and Life Sciences, Jamia Hamdard, Delhi, India Gyanu Lamichhane Division of Infectious Diseases School of Medicine, Johns Hopkins University, Baltimore, MD, USA Astrid Lewin Robert Koch Institute, Unit 16 Mycotic and Parasitic Agents and Mycobacteria, Berlin, Germany Rajesh Mani Molecular Biology and Genetic Engineering Laboratory, School of Biotechnology, Jawaharlal Nehru University, New Delhi, Delhi, India Gillipsie Minhas Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana, India Alladi Mohan Department of Medicine, Sri Venkateswara Institute of Medical Sciences, Tirupati, India Sangita Mukhopadhyay Laboratory of Molecular Cell Biology, Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad, Telangana, India K. Muniyappa Department of Biochemistry, Indian Institute of Science, Bangalore, India xxii Contributors

Prachi Nangpal Department of Biochemistry, University of Delhi South Campus, New Delhi, Delhi, India Faiza Nazar Laboratory of Molecular Cell Biology, Centre for DNA Fingerprint- ing and Diagnostics (CDFD), Hyderabad, Telangana, India Farha Naz Inflammation Biology and Cell Signaling Laboratory, ICMR-National Institute of Pathology, Safdarjung Hospital Campus, New Delhi, Delhi, India Shikha Negi Immunology Laboratory, Institute of Microbial Technology, Chandigarh, India Khairun Nisaa Department of Life Sciences, Ben Gurion University of the Negev, Beersheba, Israel Ronan F. O’Toole School of Molecular Sciences, College of Science, Health and Engineering, La Trobe University, Melbourne, VIC, Australia Department of Clinical Microbiology, School of Medicine, Trinity College Dublin, Dublin, Ireland School of Medicine, College of Health and Medicine, University of Tasmania, Hobart, Tasmania, Australia Ravi Pal Laboratory of Molecular Cell Biology, Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad, Telangana, India Graduate Studies, Manipal Academy of Higher Education, Manipal, Karnataka, India Sai Haranath Praveen Department of Pulmonary and Critical Care Medicine, Apollo Hospitals, Hyderabad, India Mamta Rani Plant Microbe Interactions Laboratory, National Institute of Plant Genome Research, New Delhi, Delhi, India Sabeeha Ali Kusuma School of Biological Sciences, Indian Institute of Technol- ogy, New Delhi, Delhi, India Ruxana T. Sadikot Section of Pulmonary, Critical Care Medicine, Emory Univer- sity, Atlanta, GA, USA Mohammad Sajid Immunology Laboratory, Institute of Microbial Technology, Chandigarh, India Jasmine Samal Inflammation Biology and Cell Signaling Laboratory, ICMR- National Institute of Pathology, Safdarjung Hospital Campus, New Delhi, Delhi, India Hubert Schäfer Robert Koch Institute, Unit 16 Mycotic and Parasitic Agents and Mycobacteria, Berlin, Germany Mohd Shariq Inflammation Biology and Cell Signaling Laboratory, ICMR- National Institute of Pathology, Safdarjung Hospital Campus, New Delhi, Delhi, India Contributors xxiii

Jyoti Sharma Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana, India Surendra K. Sharma JH Institute of Molecular Medicine, Jamia Hamdard, New Delhi, Delhi, India Departments of General Medicine & Pulmonary Medicine, JNMC, Datta Meghe Institute of Medical Sciences (DMIMS), Wardha, Maharashtra, India Department of Internal Medicine (WHO Collaborating Centre for Research & Training in Tuberculosis, Centre of Excellence for EPTB, MoH & FW, GoI), All India Institute of Medical Sciences, New Delhi, Delhi, India Tarina Sharma Molecular Infection and Functional Biology Lab, Kusuma School of Biological Sciences, Indian Institute of Technology-Delhi, New Delhi, Delhi, India Javaid A. Sheikh Department of Biotechnology, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, Delhi, India Noman Siddiqi Harvard TH Chan School of Public Health, Boston, MA, USA Bindu Singh Product Development Cell-I, National Institute of Immunology, New Delhi, Delhi, India Pooja Singh JH Institute of Molecular Medicine, Jamia Hamdard, New Delhi, Delhi, India Sanpreet Singh Immunology Laboratory, Institute of Microbial Technology, Chandigarh, India Urvashi B. Singh Tuberculosis Section, Department of Microbiology, A.I.I.M.S., New Delhi, Delhi, India Yadvir Singh Department Molecular Biology, Max Planck Institute for Infection Biology, Berlin, Germany Elizabeth Story-Roller Division of Infectious Diseases, School of Medicine, Johns Hopkins University, Baltimore, MD, USA Sharmistha Tapadar Department of Microbiology, Tripura University (A Central University), Agartala, Tripura, India Chandrakant Tarke Department of Pulmonary and Sleep Medicine, Apollo Hospitals, Hyderabad, India Manoj Thakur Department of Biochemistry, Indian Institute of Science, Bangalore, India Deeksha Tripathi Department of Microbiology, School of Life Sciences, Central University of Rajasthan, Ajmer, Rajasthan, India Prajna Tripathi National Institute of Immunology, New Delhi, Delhi, India JH Institute of Molecular Medicine, Jamia Hamdard, New Delhi, Delhi, India xxiv Contributors

Anil K. Tyagi Department of Biochemistry, University of Delhi South Campus, New Delhi, Delhi, India Guru Gobind Singh Indraprastha University, New Delhi, Delhi, India Himanshu Vashistha Viral Hepatitis Division, National Centre for Disease Con- trol, New Delhi, Delhi, India Sheeba Zarin Inflammation Biology and Cell Signaling Laboratory, ICMR-National Institute of Pathology, Safdarjung Hospital Campus, New Delhi, Delhi, India