Book Volume 3
Preface
Page: ii-iii (2)
Author: Arumugam Veera Ravi, Ramanathan Srinivasan and Arunachalam Kannappan
DOI: 10.2174/9789815080148123030002
Antimicrobial Drug Discovery Approaches, Challenges, and Development
Page: 1-44 (44)
Author: Murugesan Sivaranjani and Aaron P. White*
DOI: 10.2174/9789815080148123030004
PDF Price: $30
Abstract
The need for the identification of novel antimicrobial agents is greater than
ever due to the emergence of multidrug resistance (MDR) among clinically important
pathogens which pose serious threats to public health worldwide. Unfortunately, the
pace of discovery and development of new antimicrobial agents to treat MDR infection
has significantly slowed down. Identifying new targets and chemical classes is not
easy, and reinvestigating old strategies by testing new compounds on known targets
and expecting novel outcomes, seems not only a failure but a border on insanity. The
development of new antimicrobial agents, chiefly those with novel mechanism(s) of
action, remains essential, but this alone does not guarantee success. It is important to
explore diverse information from multiple strategies, including multi-omics,
bioinformatics, system biology and other non-conventional approaches. In this chapter,
we give a brief background on the importance of antimicrobial drug discovery, detail
several discovery platforms from target-based discovery to the current innovative
strategy being evaluated, and list the challenges alongside each platform.
Marine Natural Products as Tools for Discovering New Antimicrobial Targets
Page: 45-64 (20)
Author: Issac Abraham Sybiya Vasantha Packiavathy*, Danaraj Jeyapragash, Dharmadhas Jeba Sweetly and Arumugam Veera Ravi
DOI: 10.2174/9789815080148123030005
PDF Price: $30
Abstract
The discovery of drugs for human ailments has been greatly attributed to
nature ever since the existence of mankind. Continuous isolation of metabolites from
terrestrial resources leads to a bargaining effect on the synthesis of novel compounds.
Remarkably, marine biotope, one of nature’s resources, accommodates approximately
75% of the global surface. To acclimatize in a marine environment characterized by
unique circumstances that diverge from the individuals present in other habitation,
marine organisms occasionally accumulate structurally distinctive bioactive secondary
metabolites that are deficient in terrestrial organisms. Marine metabolites are currently
employed as the key components in pharmacological research and drug discovery,
acting as drugs and active lead molecules towards the development of novel
antimicrobials. Numerous marine metabolites that are derived from macro and
microorganisms have attained the level of clinical assessment. Hence, marine
environments are considered tools for discovering new antimicrobial agents as they
comprise a vast untapped reservoir of metabolite diversity.
An Overview of the Antimicrobials from Marine Bacteria
Page: 65-86 (22)
Author: Ramanathan Srinivasan, Arunachalam Kannappan, Xiaomeng Chen, Chunlei Shi and Xiangmin Lin*
DOI: 10.2174/9789815080148123030006
PDF Price: $30
Abstract
The marine environment comprised huge biological diversity and remained
the least explored location for prospecting novel antimicrobial agents. Marine bacteria,
in specific, are considered an essential source of therapeutically valuable biologically
active secondary metabolites. As bacteria are ubiquitous, they evolve with a certain
unique mechanism to thrive under stressful conditions like competitive habitats, much-varied temperatures, light, pH and pressure. In these harsh environments, surprisingly,
bacteria in these regions produce many natural bioactive compounds with unique
molecular scaffolds and structural complexity. This untapped biological resource may
become a source for the cure of several crises facing the world in the 21st century, such
as the emergence of multi and pan-drug-resistant bacterial and fungal pathogens and
pandemic and epidemic outbreaks of viral infections. This chapter discusses the role of
natural secondary metabolites from marine-derived bacteria as a tool in the fight
against emerging and re-emerging infectious diseases.
Marine Bacterial Viruses: The Inevitable Natural Antimicrobial Agents in the Marine Environment
Page: 87-105 (19)
Author: Anandababu Philomena Joy Lindsey, Robinson Emilin Renitta and Sevanan Murugan*
DOI: 10.2174/9789815080148123030007
PDF Price: $30
Abstract
Antimicrobial property has been the reason for investigation in several
plants and microorganisms. The health issues and environmental hazards defined by
the extensive use of chemical antimicrobials have become a buried fact due to the
emergence of bio-based antimicrobial agents. Considering the impact of chemical
antimicrobials on the environment, many natural antimicrobial agents have been
formulated and recommended for application in food systems. Several food-borne
outbreaks are associated with the intake of marine foods and are highly linked with
harmful microbial pathogens. Marine bacterial pathogens have been extensively
reported for several outbreaks in the last few decades. Vibriosis is the most devastating
disease faced by marine organisms. The associated pathogens have also been
channelized to humans through seafood consumption. There also exist some deadly
bacterial pathogens in marine environments, which are responsible for huge economic
losses in seafood processing sectors. It is high time to mitigate this bacterial jeopardy.
The extended anthropogenic activity on the coastal lines has also increased the
virulence of these bacterial pathogens by inducing multidrug resistance. Based on
several reports in the pre and post-antibiotic era, phage therapy is revitalised to
overcome the limitations encountered in antibiotic therapy. Marine bacteriophages are
documented as abundantly available viruses in the marine environment. Their
ubiquitous and inevitable nature can be utilized to engage them as natural antimicrobial
agents from the marine environment and its allied sources. This chapter summarized
the feasibility of employing bacterial viruses from the marine environment as natural
antimicrobial agents with proper evidence from the past
Marine Cyanobacteria: Sustainable Resource for Vibrant Antimicrobial Agents
Page: 106-130 (25)
Author: Sivasubramanian Santhakumari, Pandurangan Poonguzhali, Abimannan Arulkumar, Prathapkumar Halady Shetty and Madhu Dyavaiah*
DOI: 10.2174/9789815080148123030008
PDF Price: $30
Abstract
Marine cyanobacteria are oxygenic, gram-negative nitrogen-fixing
photosynthetic prokaryotes in different environments. It is a universal organism present
in aquatic and terrestrial and also extensively scattered in extreme habitats such as hot
springs, deserts and glacial environments. Growing concerns over disease outbreaks
and other environmental concerns require alternative ways that are economically
viable, sustainable, as well as feasible. Recently, cyanobacteria have achieved much
consideration because of their potential relevance in various fields, including
aquaculture, wastewater treatment, food, fodder, and the production of secondary
metabolites, including polysaccharides, vitamins, toxins, enzymes and pharmaceuticals;
they also secrete important novel bioactive antimicrobials including antibacterial,
antifungal and anti-viral compounds. The emergence of antimicrobial resistance among
pathogenic microbes against common antibiotics imposed the search for new
antimicrobial agents from natural sources. Various features of cyanobacteria, including
their ability to produce novel antimicrobials, make them suitable candidates for their
exploitation as a natural source. Hence, this chapter presents an overview of marine
cyanobacterial features, antimicrobials isolated from marine cyanobacteria, as well as
the mode of action. Among the known cyanobacterial bioactive compounds, many are
pharmacologically important and hold immense potential for drug development at the
clinical level
Reconnoitering Cell Factories of Marine Algae for Antimicrobials
Page: 131-146 (16)
Author: Jibu Thomas* and S. Jerusha Pealin Grace
DOI: 10.2174/9789815080148123030009
PDF Price: $30
Abstract
Antimicrobial compounds are groups consistent with the microorganisms
that they could potentially act against bacteria or fungi. It is expected to kill
microorganisms or inhibit their growth and activity. As the case of antimicrobial
resistance increases, nature has been generous in providing compounds with the
potential to treat various ailments and infectious diseases. Bacteria, fungi and plants are
known to own a good list of antibacterial molecules. Although research has been
carried out to reveal the antimicrobial potential of natural products, the significance of
vast terrestrial and marine Animalia has gained momentum. Though the naturally
available antimicrobial agents obtained from plants, animals and microbial sources are
considered safe in comparison with synthetic molecules, the outbreak of pathogens
needs exploration over and above the reported ones. As the synthetic antimicrobials
soon become immune to pathogens, it makes emphasis on antimicrobials from novel
origins that have a long duration of effectiveness. The marine environment houses a
wide and taxonomically diverse species of algae, mollusks, sponges, corals and
tunicates. These organisms have adapted to survive the infectious environment by
producing pharmacologically active compounds of phlorotannins, fatty acids,
polysaccharides, peptides, and terpenes that help in battling bacterial annexation. As
marine algae provide considerable opportunities in antimicrobials, the optimization in
the methodologies leading to extraction and purification plays a greater role in
capturing the antimicrobial activity of the bioactive molecules. Though an outsized
number of potential antimicrobial compounds from marine algae have been identified
and isolated, the majority of those compounds are yet to be categorized and
commercialized. Recent research in algae focused on “omics” where metagenomics,
metatranscriptomics and metaproteomics are done to understand better pathway leading
to the synthesis of various functional molecules.
Antimicrobials from Mangroves
Page: 147-170 (24)
Author: Angusamy Annapoorani, Arumugam Veera Ravi, Sundaram Janarthanan and Kandasamy Kathiresan*
DOI: 10.2174/9789815080148123030010
PDF Price: $30
Abstract
Mangroves are a promising source of antimicrobials owing to the
bioavailability of genes, plant metabolites and biological diversity. Mangroves are
known for their many biological properties, such as antibacterial, antifungal, antiviral
and anti-cancer activities etc. Besides mangroves, the microbes associated with
mangroves are called endophytes, which are proven effective antimicrobials and are
also well-known for their many other pharmacological properties. Mangrove extracts
coated with nanoparticles exhibit better antimicrobial activity due to their easy
absorption and distribution properties. The antimicrobial activity of mangroves is due
to the presence of abundant phenolic and flavonoid compounds, especially tannins, and
to the antioxidant property of the bioactive substances present in the mangroves. Thus,
mangroves have a great bioprospecting potential for developing the most potent
antimicrobials to treat pathogenic bacteria, viruses and fungi. This chapter deals with
the antibacterial, anti-viral, anti-mycotic, anti-virulence and anti-biofilm properties of
mangrove extracts and mangrove endophytes against various pathogenic and
multidrug-resistant microbes. In addition, patenting of natural compounds from
mangroves and their endophytes, as well as metabolomics and proteomics, are also
discussed in this chapter.
A Recent Update on Sponge Bioprospecting and its Antimicrobial Properties: Their Biological Mode of Action
Page: 171-200 (30)
Author: Balraj Sudha, Kanagaraj Suganya, Bishwambhar Mishra, Govindugari Vijaya Laxmi, Sanjeeb Kumar Mandal*, Sanjay Kumar and Sundaravadivelu Sumathi
DOI: 10.2174/9789815080148123030011
PDF Price: $30
Abstract
In recent decades, both the growing global resistance to existing antibiotics
and the shortage of new groups of compounds identified have become a public health
concern. In order to solve it, researchers are now focusing their attention on
unconventional sources, including microbes from harsh environments. In this context,
the aim of this study was to determine whether marine sponges have the ability to
inhibit the growth of microorganisms that are terrestrial in origin and pathogenic to
humans. The majority of these chemicals have so far been found in marine
invertebrates, primarily sponges. Marine sponges are a rich source of structurally
specific natural substances, some exhibiting a diverse variety of biological activities.
Also, excellent sponge drug candidates are often overlooked because the sponges are
either rare or difficult to obtain, or both. Sponges have piqued the interest of scientists
who want to learn more about the associated microbial community and the useful
metabolites they produce, which can be used in pharmaceutical and biotechnological
applications. The ecological importance of mutualistic relationships between marine
sponges and their related microbes cannot be overstated. These bioactive compounds
from microbes protect their hosts from a variety of microbial diseases. These results
indicate that the antimicrobial properties of marine sponge extracts may be used as a
complementary or replacement method for treating microbial infections.
Antimicrobial Peptides: A Recent Update in the Pros, Cons, and Opportunities as Potential Antimicrobial Agents from Marine Resources
Page: 201-227 (27)
Author: Arunachalam Kannappan*, Ramanathan Srinivasan, Sethuraman Sathya and Chunlei Shi*
DOI: 10.2174/9789815080148123030012
PDF Price: $30
Abstract
The emergence of multidrug-resistant (MDR) among pathogenic organism
puts human and animal lives at stake. As a result of that, researchers in the scientific
community tirelessly made efforts to search for novel antimicrobial agents to combat
the pathogenesis of multidrug-resistant pathogens. Marine environment represents a
vast diversity of lives that interact with each other and thus have to protect themselves
against infectious pathogens. Hence, they present an armamentarium of diversified
biomolecules with different mechanisms of action, which aids the survival of the host
in the very same environment. Among the natural biomolecules, antimicrobial peptides
(AMPs) gain more attention owing to their potential action as antimicrobial agents
against several infectious diseases. With the emergence of MDR pathogens, AMPs are
currently deemed to be the next generation of antibiotics. The quest of these AMPs was
initially focused on the terrestrial environment for years. By knowing the presence of
the least explored and diverse organism, the focus on the quest of AMPs is now
heading toward the marine ecosystem. The current chapter focuses on the benefits,
confronts and chances of using AMPs against MDR pathogens, and also emphasizes the need and importance of designing a focused development tactic to support the
advancement and potential application of AMPs in medicine.
Antimicrobial Peptides from Marine Invertebrates
Page: 228-256 (29)
Author: Srichandan Rath, Subhashree Jena, Sankar Kanchana and Muthuvel Arumugam*
DOI: 10.2174/9789815080148123030013
PDF Price: $30
Abstract
This chapter centers on the novel marine metabolites from marine
organisms, especially peptides and other therapeutic agents. The major component of
the innate immune defense system, also regarded as the first line of defense, is the
antimicrobial peptide, which not only boosts resistance but also displays promising
curative properties. The isolation, potential antimicrobial activity, various properties,
mechanism and sources of diversified antimicrobial peptides distributed in various
phyla of marine invertebrates, along with their potential role in the therapeutic arena,
are explored. The most popular conotoxin peptide Zincnotide was available as a drug
(Prialt®) and entered the market as a potent analgesic agent. Ethionamide (Trecator®),
a nicotinamide derivative, isolated from porifera possessing antibacterial activity, is
used to treat tuberculosis. Similarly, a number of peptides have been reported for
exhibiting antimicrobial activities in marine organisms. Hence, the present chapter is
mainly focusing on the list of marine invertebrates’ antimicrobial peptides and their
therapeutic applications.
Marine Biosurfactants as Potential Agents to Combat Multi-Drug Resistant Pathogens
Page: 257-277 (21)
Author: Pandi Saravana Kumari and Sevanan Murugan*
DOI: 10.2174/9789815080148123030014
PDF Price: $30
Abstract
Increasing threats due to microbial infections during disease outbreaks
resulted in excessive usage of antibiotics. Even during viral disease outbreaks,
antibacterial agents are widely prescribed to control bacterial co-infections as a
precautionary measure. Moreover, inappropriate use of antibiotics steered towards the
development of resistance against a diverse group of antibiotics. Dispersion of
multidrug-resistant (MDR) pathogens in the environment is one of the reasons for the
development of multi-drug resistance among opportunistic and commensal organisms.
This poses a major risk to the healthcare sector. Excessive usage of antibiotics not only
results in antibiotic resistance but also in multiple healths associated diseases in
humans, such as ulcers, abdominal cramps and discomfort, and anaphylactic shock.
Hence, a safe, target-oriented drug with or without minimum side effects is demanded
to control multi-drug resistant (MDR) pathogens. The marine environment hosts the
habituation of several plants, animals, and microorganisms. It also harbors novel,
potent therapeutic agents against emerging pathogens. Recent research reports state that
biosurfactants from marine bacteria, fungi, algae, animals, and plants possess targeted
activity against human pathogens. These biosurfactants restrict the growth of microbial
pathogens by several mechanisms. Biofilm formation is the major mechanism adopted
by many MDR strains to overcome antibiotic treatment. Biosurfactants are reported to
prevent even compact biofilms by preventing the adhesion of pathogenic bacteria to the
host system or clinical devices. Also, they inhibit cell-to-cell signalling and down-regulate the genes coding for biofilm formation, thereby ensuring the complete removal
of MDR pathogens. Novel biosurfactants from marine sources render a wide
opportunity in drug selection to combat multi-drug resistant organisms.
Bioactive Polysaccharides with Antimicrobial Proficiency from Marine Environment
Page: 278-303 (26)
Author: Arumugam Priya, Nagaiah Hari Prasath and Shunmugiah Karutha Pandian*
DOI: 10.2174/9789815080148123030015
PDF Price: $30
Abstract
Marine environment upholds vast biodiversity, which also acts as a treasurer
of a huge variety of bioactive molecules. Bioactive components of marine origin range
from peptides, lipids, fatty acids, proteins, minerals, phenolic compounds, vitamins,
terpenoids, polyketides, polysaccharides etc. Marine-derived peptides have been
explored to a larger extent for their biological applications. In recent years,
polysaccharides, one of the essential macromolecules in all forms of living, have been
gaining attention for their relevance in biological applications. Among the
polysaccharides derived from various living forms, marine-derived polysaccharides are
effective in terms of their biological activities owing to their structural diversity,
composition, availability etc. Marine polysaccharides exhibit a broad spectrum of
biological and pharmacological activities ranging from anti-inflammatory, antioxidant,
anticancerous, antidiabetic, antioxidant, antidiabetic and immunomodulatory activities.
Additionally, these bioactive polysaccharides also exert antimicrobial activities against
a broad range of clinically important pathogenic organisms. Due to their excellent
antimicrobial activities, marine polysaccharides, their sulfated derivatives and
polysaccharide-based nanoparticles are gaining attention in biomedical applications
such as wound dressing, drug delivery, tissue engineering etc.
Synthetic Derivatives from Marine Natural Products as Potential Antimicrobial Drugs
Page: 304-321 (18)
Author: Ravindran Durgadevi and Arumugam Veera Veera Ravi*
DOI: 10.2174/9789815080148123030016
PDF Price: $30
Abstract
The marine environment havens a massive number of species that are the
source of a wide range of structurally diverse bioactive secondary metabolites. The
importance of marine natural products (MNPs) in drug discovery has been documented
extensively with their impact on the development of existing drugs. Despite the
promising activity of MNPs, most of them suffer from their complex structures,
instability, and poor solubility. The synthetic derivatives of natural products cover the
chemical derivatization of scaffolds isolated from marine sources and are highly
applicable as chemical biosynthesis and structural modifications provide new insights
into the bioactivities and the dealings against specific targets that are important for
exploring the indefinite chemical space. Also, engineering of the biosynthetic pathway
has shown its ability to drive analogies arising from a variety of alterations, including
replacement of residues, feeding with non-natural precursors, and enzyme knockout.
Such arrays of synthetic compounds execute functionally distinct biological activities
against various microbial pathogens, considering MNPs valuable products in the
current era of drug discovery. This chapter describes the strategies and principles for
the development of synthetic drugs, as divulged by several fruitful medicines that are
derived from marine origin.
Marine Metabolites: An Untapped Resource for Combinatorial Approaches against Antimicrobial Resistance
Page: 322-344 (23)
Author: Loganathan Vigneshwari, Arumugam Priya and Sivasamy Sethupathy*
DOI: 10.2174/9789815080148123030017
PDF Price: $30
Abstract
Nanomedicine from Seaweed and its Sulfated Polysaccharide Mediated Silver Nanoparticles for Microbial Disease Control
Page: 345-368 (24)
Author: Ravichandran Anjali, Subramanian Palanisamy, Avudaiyan Muthamil Selvi, Manoharn Vinosha, Muthushanmugam Manikandakrishnan, Periyannan Rajasekar, Sonaimuthu Mohandoss, SangGuan You and Narayanasamy Marimuthu Prabhu*
DOI: 10.2174/9789815080148123030018
PDF Price: $30
Abstract
Worldwide, aquaculture organisms are often infected by viruses, bacteria,
fungi, and parasites. These organisms are responsible for the high mortality, leading to
major financial loss in this industry. Controlling microbial diseases in aquaculture is
not that easy; it is much more difficult than prevention because it is a complex
environment. Farmers are using different strategies to overcome this issue; however,
recognizing new dietary supplements for preventing the disease is always helpful to
aquaculture farmers. More recently, the bioreduction of nanoparticles using seaweed
extract and its sulfated polysaccharides are fascinated because of the presence of
various bioactive properties. Also, it is well-accepted that the green chemistry approach
is a superior alternative to the synthesis of non-toxic nanoparticles. This chapter covers
the major microbial disease in aquaculture and its management, the application of
nanoparticles in aquaculture, the importance of seaweed and its sulfated
polysaccharide-mediated silver nanoparticles and its role in Vibriosis and WSSV
disease control in aquaculture. This chapter provides a superior understanding to the
researchers for formulating novel health supplements using seaweed and its sulfated
polysaccharides mediated nanoparticles to overcome bacterial and viral disease in
aquaculture.
Preclinical Drug Entities in Clinical Trial Pipeline from Marine Source
Page: 369-388 (20)
Author: Suganya Kannan*, Karvannan Sevugamurthi, Jeyakumar Balakrishnan, Ambujam Govindasamy and Murugan Marudhamuthu
DOI: 10.2174/9789815080148123030019
PDF Price: $30
Abstract
The massive increase in the world’s population has placed an undue strain
on the available resources for pharmaceuticals. As a result, drug producers are
constantly on the lookout for new resources that will allow them to build effective and
safe pharmaceuticals to meet the growing demands of the world’s population.
However, three fourth of the earth’s surface is covered by the marine environment,
studies into the pharmacology of marine creatures have been limited, and much of what
has been discovered is still undiscovered. The marine environment is a plethora and
diversified source of novel medications to treat important diseases like cancer and
malaria, among others. Marine natural products have distinct, previously unexplored
diversifications as well as a diverse range of intriguing biological potentialities that are
characterized by unique mechanisms of action. Recently discovered and preclinically
researched marine bioactive antimicrobials are the focus of this chapter.
Recent Update on the Patents of Antimicrobial Marine Natural Products
Page: 389-408 (20)
Author: Alwar Ramanujam Padmavathi*, Dhamodharan Bakkiyaraj and Sathya Narayanan Gokul
DOI: 10.2174/9789815080148123030020
PDF Price: $30
Abstract
Marine environment has long been shown as the source of diverse organisms
and niche for numerous bioactive agents. Marine natural products are of recent interest
attributing to their novelty and abundant potential in the field of medicine as well as
others. In spite of this recent attention, the marine environment still exists as an under-explored and untapped resource for bioactive agents, highlighting the presence of
plentiful opportunities. Bioactive molecules of marine origin have been frequently
reported from the microorganisms associated with marine sediments, seawater, coral
and its mucus; higher-order marine organisms, mangroves, sponges, seaweeds and sea
grasses, etc. Last decade has shown copious publications reporting the bioactive
potentials of marine natural products such as antimicrobial, antiviral, antiparasitic,
anticancer, antioxidant, anti-inflammatory and anti-infective properties. Recent studies
have also opened an avenue in marine natural product research where the discovered
natural products are chemically modified to attain increased bioactivity. Such modified
or altered marine natural products were of great demand in pharmaceutical, food,
cosmetic and chemical industries, and hence protected by product and process patents.
This chapter summarizes the intellectual property rights in the form of patents
protecting marine natural products with antimicrobial potentials, including
antibacterial, antifungal and antibiofilm activities. This chapter also highlights the
patents and applications of modified or semi-synthetic agents related to marine natural
sources with antimicrobial properties.
Subject Index
Page: 409-414 (6)
Author: Arumugam Veera Ravi, Ramanathan Srinivasan and Arunachalam Kannappan
DOI: 10.2174/9789815080148123030021
Introduction
While the world is grappling with the growing problem of antibiotic resistance, marine organisms offer a promising solution with their diverse repertoire of bioactive compounds. This thematic volume explores the untapped potential of marine organisms in the fight against microbial threats. The focus of the 17 featured chapters lies in highlighting the vast array of antimicrobial agents that can be found within marine environments. The chapters provide in-depth knowledge about the latest discoveries, advancements and future needs in antimicrobial research. Readers will learn about astonishing discoveries of natural compounds with remarkable antimicrobial properties and sources. The list of agents covered in the book includes synthetic derivatives, bioactive polysaccharides and marine viruses. The book also includes chapters that cover various stages of the antimicrobial drug development process, providing an overview of recent antimicrobial agents derived from marine organisms, preclinical studies and the identification of patented drugs sourced from the ocean. Furthermore, the book sheds light on the diverse applications of these marine-derived compounds, spanning the fields of medicine, agriculture, and industry. Professionals in the fields of microbiology, marine biology, pharmaceutical sciences, and drug development will gain valuable insights into the use of marine organisms as a source of antimicrobial agents.