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Current Research, Technology and Education Topics in Applied Microbiology and Microbial Biotechnology
A. Méndez-Vilas (Ed.)
_______________________________________________________________________________________
Seaweeds: A novel, untapped source of drugs from sea to combat
Infectious diseases
S. Chanda*, Dave R, Kaneria M and Nagani K
Phytochemical, Pharmacological and Microbiological Laboratory, Department of Biosciences, Saurashtra University,
Rajkot 360 005, Gujarat, India
* author for correspondence email:[email protected]
The discovery and development of antibiotics are among the most powerful and successful achievements of modern
science and technology for the control of infectious diseases. Prolonged usage of broad – spectrum antibiotics has led to
the emergence of drug resistance. There is a tremendous need for novel antimicrobial agents from different sources. The
biodiversity of marine ecosystem provides an important source of chemical compounds which have many therapeutic
applications. Seaweeds or marine algae have been reported to contain many important compounds which act as antibiotics,
laxatives, anticoagulants, anti-ulcer products and suspending agents in radiological preparations. Many substances
obtained from marine algae such as alginate, carrragenean and agar as phycocolliods have been used for decades in
medicine and pharmacy. More and more chemist and biologist pay attention to the constituents of the algae; if their natural
products are explored, they may lead to an efficient lead for the discovery of new drug molecules against several
pathogens causing infectious diseases.
Key words: Infectious diseases; seaweeds; antimicrobial; marine algae
1. Synthetic dominance: growing threat of antimicrobial resistance
Mankind's discovery of antibiotics ushered in a new age of medicine during the 19th century, an age wherein many
predicted an end to diseases that had plagued the mankind for centuries with the appearance of penicillin during World
War II as the first miracle drug [1]. From 1940s to almost 1980s many classes of antibiotics discovered have helped
tame many of the terrors of human health. The use of these "wonder drugs", combined with improvements in sanitation,
housing, nutrition, and the advent of widespread immunization programmes, led to a dramatic drop in deaths from
diseases that were previously widespread, untreatable, and frequently fatal. Over the years, antimicrobials have saved
the lives and eased the suffering of millions of people.
Advances in synthetic chemistry for identification of many key chemical molecules offered more opportunities to
develop novel compounds. Numerous drugs like sulphonamides, isoniazid, anti-psychotics, anti-histamines and
penicillin were developed from thousands of chemicals [2]. Emergence of modern pharmaceutical industry is an
outcome of all these different activities that developed potent single molecules with highly selective activity for a wide
variety of ailments. These successes resulted in reduced interest in natural products drug discovery. Thus, herbal
medicines became the domain of 'old wives tales'.
It was not until the 1970s that antibiotic resistance was considered to be a real threat. In the past, medicine and
science were able to stay ahead of this natural phenomenon through the discovery of potent new classes of
antimicrobials, a process that flourished from 1930-1970 and has since slowed to a virtual standstill, partly because of
misplaced confidence that infectious diseases had been conquered, at least in the industrialized world. In just the past
few decades, the development of resistant microbes has been greatly accelerated by several concurrent trends like
urbanization, pollution, AIDS epidemic, etc. These have worked to increase the number of infections and thus expand
both the need for antimicrobials and the opportunities for their misuse.
Recently, infections have become the leading cause of death world-wide which has led to an increase in antibacterial
resistance, making it a global growing problem [3]. More and more bacteria are developing resistance to antibiotics
conferred by randomly mutated genes [4]. Each year infectious diseases cause 14 million deaths worldwide, with
mortality increasing even in the United States at an annual rate of 4.8 percent. In 2000, the World Health Organization
(WHO) estimated that pneumonia, diarrhoeal disease, and tuberculosis accounted for more than half the deaths due to
infectious disease worldwide. The problem is worsened by antibiotic resistance, as well as the emergence of new
pathogens with the potential for rapid global spread [5]. In addition to this problem, antibiotics are sometimes
associated with adverse effects on the host including hypersensitivity, immume-supression and allergic reactions [6].
Now, Scientists accepted that antibiotics will leave healthcare professionals without effective therapies for bacterial
infections for example Staphylococcus aureus. It is estimated that about half of all strains found in many medical
institutions are resistant to antibiotics such as methicillin [7]; or enterococci, which are resistant to widely effective
antibiotic, vancomycin [8]. Thus, there is an urgent need to discover new antimicrobial compounds with diverse
chemical structures and novel mechanisms of action for new and re-emerging infectious diseases. The new therapeutic
agents should be effective and have a novel mode of action that render them impervious to existing resistance
mechanisms. Not only drugs from natural sources have new structural features, with novel biological activity but
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phytochemicals derived from them are also extremely useful as lead structures for synthetic modification and
optimization of bioactivity.
2. Need of the hour
We are now at the crucial stage where it is essential to explore new strategies in order to combat infectious diseases.
The oceans represent virtually untapped resource from which novel bioactive compounds can be discovered. The
marine environment representing approximately half of the global biodiversity, is an enormous resource for new
compounds. Sea weeds or marine algae are potentially prolific sources of highly bioactive secondary metabolites that
might represent useful leads in the development of new pharmaceutical agents. Many reports have been published about
isolated compounds from algae with biological activity, demonstrating their ability to produce metabolites, with high
complexity and unlimited diversity of pharmacological and/or biological properties.
3. Seaweeds
Seaweeds belong to a group of plants known as algae. Seaweeds are classified as Rhodophyta (red algae), Phaeophyta
(brown algae) or Chlorophyta (green algae) depending on their nutrient, pigments and chemical composition. Like other
plants, seaweeds contain various inorganic and organic substances which can benefit human health [9]. Seaweeds are
considered as a source of bioactive compounds as they are able to produce a great variety of secondary metabolites
characterized by a broad spectrum of biological activities. Compounds with antioxidant, antiviral, antifungal and
antimicrobial activities have been detected in brown, red and green algae [10, 11]. Some promising red, brown and
green algae of Gujarat coast region are shown in Fig. 1.
The environment in which seaweeds grow is harsh as they are exposed to a combination of light and high oxygen
concentrations. These factors can lead to the formation of free radicals and other strong oxidizing agents but seaweeds
seldom suffer any serious photodynamic damage during metabolism. This fact implies that seaweed cells have some
protective mechanisms and compounds [12].
In recent years, several marine bacterial and protoctist forms have been confirmed as important source of new
compounds potentially useful for the development of chemotherapeutic agents. Previous investigations of the
production of antibiotic substances by aquatic organisms point to these forms as a rich and varied source of antibacterial
and antifungal agents. Over 15,000 novel compounds have been chemically determined. Focusing on bioproducts,
recent trends in drug research from natural sources suggest that algae are a promising group to furnish novel
biochemically active substances [13].
Seaweeds or marine macro algae are the renewable living resources which are also used as food and fertilizer in
many parts of the world. Seaweeds are of nutritional interest as they contain low calorie food but rich in vitamins,
minerals and dietary fibres [14]. In addition to vitamins and minerals, seaweeds are also potentially good sources of
proteins, polysaccharides and fibres [15]. The lipids, which are present in very small amounts, are unsaturated and
afford protection against cardiovascular pathogens.
4. Seaweeds - Diversity in marine ecosystem
Algae are known to be comparatively sensitive to chemicals [16]. Their ecological position at the base of the aquatic
food chain and their essential roles in nitrogen and phosphorus cycling are critical to aquatic ecosystems [17].
Moreover, the alternation of species composition in an aquatic community as a result of toxic stress may affect the
structure and function of the whole aquatic ecosystem [18].
The diversity of life in the terrestrial environment is extraordinary; the greatest biodiversity is in the world’s oceans,
with 34 of the 36 phyla of life represented. The oceans cover more than 70% of the earth’s surface and contain more
than 300,000 described species of plants and animals [19, 20]. The marine environment represents a treasure of useful
products awaiting discovery for the treatment of infectious diseases. Ecological pressures, including competition for
space, the fouling of the surface, and predation have led to the evolution of unique secondary metabolites with various
biological activities [21]. The important role of these secondary metabolites in the control of infectious microorganisms
was for many years largely unnoticed.
5. Seaweeds – an anti infectious agent
The revolutionized therapy of infectious diseases by the use of antimicrobial drugs has certain limitations due to
changing patterns of resistance in pathogens and side effects they produce. These limitations demand for improved
pharmacokinetic properties, which necessitates continued research for the search of new antimicrobial compounds for
the development of drugs. Seaweeds are used in traditional remedies in many parts of the world. The production of
inhibitory substances by seaweed was noted as early as in 1917.
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Fig 1. Some promising marine macro algae
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6. Seaweeds – biological activities and bioactive compounds
The extracts and active constituents of various algae have been shown to have antibacterial activity in vitro against
Gram-positive and Gram-negative bacteria; some examples are given in Table 1. The production of antimicrobial
activities was considered to be an indicator of the capacity of the seaweeds to synthesize bioactive secondary
metabolites [22]. There are numerous reports of compounds derived from macroalgae with a broad range of biological
activities, such as antibacterial [23], antivirals [24], antitumorals [25], anticoagulant [26] and antifouling [27].
Compounds with cytostatic, antiviral, antihelminthic, antifungal and antibacterial activities have been detected in green,
brown and red algae [28]. Also, considering their great taxonomic diversity, investigations related to the search of new
biologically active compounds from algae can be seen as an almost unlimited field.
Among the different compounds with functional properties, antioxidants are the most widely studied. Moreover, the
important role of antioxidants in human health has been demonstrated thus increasing the interest in such products and
their demand by consumers. Marine algae serve as important resources for bioactive natural products [29]. Brazilian red
algae have been found to have phenolic substances. Kappaphycus alvarezzi has nutritive and antioxidant property;
different parts of the thalli are also known to differ in their antimicrobial potential [30].
Similarly, some micro-algae contain and/or excrete pharmacologically active compounds. For example, the
dinoflagellates Gymnodinium sp. and Gonyaulax sp. produce an alkylguanidine compound that affects the central
nervous system. Brominated bi-indoles of Rivularia firma show pharmacological activity. Gracilaria lichenoides, a red
alga, excretes prostaglandins and the compound C20 [31]. Seaweeds are known to contain reactive antioxidant
molecules, such as ascorbate and glutathione (GSH) when fresh, as well as secondary metabolites, including
carotenoids (α- and β-carotene, fucoxanthin, astaxanthin), mycosporine-like amino acids (mycosporine-glycine) and
catechins (e.g., catechin, epigallocatechin), gallate, phlorotannins (e.g., phloroglucinol), eckol and tocopherols (α-, χ-, δtocopherols) [32]. Brown-algal polyphenols phlorotannins worked as antioxidants and antibacterial compounds [33].
7. An attempt at integration — Conclusion
Research is a crucial part of the response to new and emerging diseases. A sustained, forward-thinking applied research
programme would enable scientists to identify the weak links in the armour of emerging microbes, create novel ways to
fight microbial foes, and evaluate the preventive power of new approaches. The priority for the next decades should be
focused in the development of alternative drugs and/or the recovery of natural molecules that would allow the consistent
and proper control of pathogen-caused diseases. The general trend to more widespread antibiotic resistance is relentless
and if it continues unabated, deaths from what were previously treatable infections will occur with increasing
frequency. The initiatives must be implemented now because the battle against antibiotic resistance is being lost.
Complacency and delay will have major detrimental effects on future public health. Seaweeds may be an answer to
unsolved and growing problem of resistance, a novel untapped source to combat infectious diseases.
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Table 1 List of some reported algae for antimicrobial activity
No
1
2
3
4
Name of algae
Microorganisms
Ceramium
indica,
Enteromorpha
intestinalis, Ulva lactuca, Gelidiella
acerosa, Corallina officinalis, Gracilaria
corticata, Sargassum sp., Galaxaura
oblongata, Grateloupia sp., Ceramium
indica, Laurentia pedicullata, Sargassum
sp., Padina gymnospora, Stoechospermum
marginatum, Cystoseira sp. Caulerpa
racemosa,
Caulerpa
scalpelliforrmis,
Spathoglossum variabile, Halimeda tuna,
Gelidiopsis gracilis, Iyengaria stellata,
Gelidium
sp.,
Udotea
indica,
Gastroclonium iyengarii, Heterosiphonia
sp.
Corallina officinalis, Cystoseira barbata,
Dictyota dichotoma, Halopteris filicina,
Cladostephus spongiosus f. verticillatus,
Ulva rigida
Gracilaria tikvahiae, Ulva lactuca, Ulva
fasciata, Sargassum fluitans
Ulva lactuca, Padina gymnospora,
Sargassum wightii, Gracilaria edulis
5
Trichodesmium erythraeum
6
Sargassum sp.
7
Eucheuma denticulatum
Ulva rigida, Enteromorpha linza, Padina
pavonica, Colpomenia sniosa, Dictyota
linearis,
Dictyopteris
membranacea,
Cystoseira
mediterranea,
Ectocarpus
siliculosus, Ceramium rubrum, Gracilaria
gracilis, Acanthophora nojadiformis
8
9
Kappaphycus sp., Padina sp.
10
Sargassum
dentifolium,
papillosa, Jania corniculata
11
Colpomenia sinuosa, Dictyota dichotoma,
Dictyota dichotoma var. implexa, Petalonia
fascia, Scytosiphon lomentaria
12
Synechocystis sp., Himanthalia elongata
13
14
Laurencia
Microchaete tenera, Nitella tenuissima,
Sphaeroplea annulina
Ulva fasciata, Caulerpa cupressoides,
Referen
ces
B. cereus ATCC11778, M. flavus ATCC10240, K.
pneumoniae NCIM 2719, P. testosteroni NCIM5098,
C. freundii ATCC10787
[23]
S. aureus, M. luteus, E. faecalis, E. coli, E. aerogenes,
E. coli O157:H7
[34]
E. coli, S. aureus, S. enteriditis, S. epidermidis, P.
aeruginosa, S. faecalis, C. albicans
S. aureus, V. cholerae, S. dysentriae, S. bodii, S.
paratyphi, P. aeruginosa, K. pneumoniae
B. subtilis MTCC441, E. faecalis ATCC29212, S.
aureus ATCC 25923, E. coli ATCC25922, K.
pneumoniae ATCC15380, P. vulgaris MTCC1771, P.
aeruginosa ATCC27853, E. amylowora MTCC 2760,
S. typhimurium, T. rubrum 57/01, T. mentagrophytes
66/01, T. simii 110/02, Scopulariopsis sp. 101/01, A.
niger MTCC1344, A. flavus, B. cinerea, C. albicans
MTCC227
B. subtilis CCR 12, E. coli MTCC 443, S. aureus
MTCC 96
S. aureus, S. Pyogenes
Candida sp., E. faecalis, S. aureus, S. epidermidis, P.
aeruginosa, E. coli
P. fluorescence, S. aureus, V. cholera, P. mirabilis, B.
megaterium, Citroacitro sp., Entrobacter sp., K.
pneumoniae, E. coli, S. typhimurium, S. fexneri, P.
vulgaris, P. aeruginosa, V. cholera
B. subtilis, S. albus, S. faecalis, E. coli, C. albicans, A.
flavus
B. subtilis ATCC6633, S. aureus ATCC6538P, E.
aerogenes ATCC 13048, E. coli ATCC29998, P.
vulgaris ATCC6897, S. typhimurium CCM 583,
methicillin-oxacillin- resistant S. aureus ATCC43300,
E. coli (O157: H7) RSSK 232, C. albicans ATCC10239
S. aureus ATCC25923, E. coli ATCC11775, C.
albicans ATCC 60193, A. niger ATCC16404
P. vulgaris, B. cereus, E. coli, P. aeruginosa, A. niger,
A. flavus, R. nigricans
B. subtilis, S. epidermidis, S. aureus, C. freundii, E.
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[40]
[41]
[42]
[43]
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15
16
17
Caulerpa
prolifera,
Gracilaria
domingensis, Gracilaria sp., Amansia
smultifida
S. marginatum, St. marginatum, P.
tetrastromatica, P. gymnospora, C.
implexa, D. australis, D. bartayresiana, S.
aspermum,
Asparagopsis
taxiformis,
Amphiroa fragilissima, Jania reubens,
Caulerpa racemosa, Caulerpa peltata,
Caulerpa taxifolia, Codium fragile,
Chlorodesmis fastigiata
Gracilaria corticata, Ulva fasciata,
Enteromorpha compressa
Valonia
aegrophila,
Ulva
pertusa,
Halimeda opumtia, Halimeda tuna,
Caulerpa racemosa, Caulerpa mexicana
18
Cystoseira tamariscifolia
19
Spirulina platensis
20
Dictyopteris membranaceae, Cystoseira
barbata
21
Enteromorpha linza
22
Jania rubens
23
Polysiphonia virgata
24
Ulva lactua, Halimeda gracilis, Gracilaria
edulis, Hypnea musiformis, Turbinaria
conoides, Sargassum myricystum
25
Gracilaria changii
26
Ulva fasciata
27
Dictyota acutiloba
478
coli, E. aerogenes, K. pneumoniae, M. morganii, P.
aeruginosa, S. typhi, S. typhimurium, S. enteritidis, S.
cholerae-suis, S. marcescens, V. cholerae
B. subtilis, E. coli, Pseudomonas sp., S. pyrogenes, S.
aureus, P. vulgaris, K. pneumoniae, S. morganii, C.
albicans.
[47]
V. alginolyticus, P. aeruginosa, A. hydrophila, E.
tarda, P. fluorescens, A. hydrophila
[48]
S. aureus, B. subtilis, E. coli, C. albicans
[49]
S. cerevisiae, C.
albicans, Debaryomyces sp.,
Kluyveromyces sp strains), A. flavus, Penicillium sp
S. faecalis, B. subtilis, S. aureus, S. epidermidis, P.
aeruginosa, E. aerogenes, E. cloacae, E. coli, S.
typhimurium, P. vulgaris, C. albicans
S. faecalis, B. subtilis, S. aureus, S. epidermidis, P.
aeruginosa, E. cloacae, E. coli, S. typhimurium, C.
albicans
S. aureus, S. epidermidis, S. fecalis, B. subtilis, S.
typhimurium, P. aeruginosa, E. cloacae, E. coli, C.
albicans
S. aureus, S. epidermidis, S. faecalis, B. cereus, B.
subtilis, S. typhimurium, P. aeruginosa, E. cloacae, E.
coli, C. albicans
M. smegmatis, M.tuberculosis, multidrug resistant M.
tuberculosis
E. coli, P. aeruginosa, S. aureus, K. pneumoniae, E.
faecalis
S. aureus, P. aeruginosa, P. mirabilis, E. coli, A.
calcoaceticus, S. saprophyticus, S. marcescens, K.
pneumoniae, A. nitratus, S. paratyphyi B, B.
licheniformis, Micrococcus sp., S. epidermidis, C.
preundii, E. enterocolitica, S. typhi, B. pseudomallei,
B. subtilis, Erwinia sp., B. cereus, E. aerogenes, C.
albican, R. rubra, C. neoformans, S. cerevisiae, T.
viride, Rhizophus sp., Mucor sp., Penicillium sp.,
Fusarium sp., T. mentagrophytes, F. oxysporium, A.
niger, A. flavus
V. parahaemolyticus, V. alginolyticus, V. vulnificus
methicillin resistant S. aureus, methicillin susceptible S.
aureus, Enterobacter sp., P. aeruginosa, S. typhi, B.
subtilis, K. pneumoniae, C. albicans, A. niger
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