Pigments From Soil Bacteria and Their Therapeutic Properties - Mini Review

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Current Microbiology

https://doi.org/10.1007/s00284-018-1557-2

REVIEW ARTICLE

Pigments from Soil Bacteria and Their Therapeutic Properties: A Mini


Review
Roqayya Mumtaz1,3 · Samina Bashir1,3 · Muhammad Numan1 · Zabta Khan Shinwari2 · Muhammad Ali1

Received: 20 March 2018 / Accepted: 22 August 2018


© Springer Science+Business Media, LLC, part of Springer Nature 2018

Abstract
Advancement in research on dyes obtained from natural sources e.g., plants, animals, insects and micro-organisms is widen-
ing the application of natural dyes in various fields. The natural dyes substituted their synthetic analogs at the beginning of
twentieth century due to their improved quality, value, ease of production, ease of dyeing and some other factors. This era
of dominance ended soon when toxic effects of synthetic dyes were reported. In the last few decades, pigments from micro-
organisms especially soil derived bacteria is replacing dyes from other natural sources because of the increasing demand for
safe, non-toxic, and biodegradable natural product. Apart from application in agriculture practices, cosmetics, textile, food
and paper industries, bacterial pigments have additional biological activities e.g., anti-tumor, anti-fungal, anti-bacterial,
immunosuppressive anti-viral, and many more which make them a potential candidate for pharmaceutical industry. Optimi-
zation of culture conditions and fermentation medium is the key strategies for large scale production of these natural dyes.
An effort has been done to give an overview of pigments obtained from bacteria of soil origin, their dominance over dyes
from other sources (natural and synthetic) and applications in the medical world in the underlying study.

* Roqayya Mumtaz
rouqyamumtaz455@gmail.com
* Samina Bashir
saminabashir19@yahoo.com
Zabta Khan Shinwari
shinwari2008@gmail.com
1
Department of Biotechnology, Quaid-i-Azam University,
Islamabad, Pakistan
2
Qarshi University, Lahore, Pakistan
3
Department of Biotechnology, Faculty of Biological
Sciences, Quaid-i-Azam University, Islamabad 45320,
Pakistan

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R. Mumtaz et al.

exploitation of micro-organisms for the presence of medici-


Introduction
nal entities [9].
Despite the fruitful history, natural color industry was
Background of the Study
domineered by the advent of synthetic dye industry [10].
Problems like lack of plantation of dye producing plants,
Bacteria is considered as the most numerously culturable
reduced accessibility of dye producing materials due to dif-
soil micro-organism, ranging from fragile (damaged and
ficulty in collection, low color yield, dyeing process com-
sometimes killed by slight changes in soil environment)
plexity, limited number and non-reproducibility of dyes and
to tough (tolerate severe cold, heat and drying). Some can
sometimes poor fastness properties were the few main rea-
wait for suitable conditions, so lie quiescent for years. Oth-
sons. Further development of synthetic dyes at the beginning
ers can either get nitrogen directly from the environment
of the twentieth century improved the value and quality of
or from the breakdown of toxic materials [1]. Bacteria are
the dyes and made them more acceptable than their natural
usually thought to be disease causing microbes and its true
counterparts.
in some cases but many are harmless or even beneficial
The era of synthetic dye dominance over the whole dye
for the mankind. Researchers are focusing on the positive
industry ended only a decade ago when the toxic effects of
side of this creature and have discovered amazing abilities
dyes during wearing were reported and created a serious
that are interesting in their own way [2]. Pigment produc-
concern [11]. It was also reported that these dyes affect the
tion by bacteria is the area of great interest from the very
aquatic fauna by decreasing the amount of dissolved oxygen
beginning of Bacteriology, possibly because it is the most
in water [12]. In the 1960s, the environmental activists in US
readily observed microbial characteristics [3]. Awareness
took action against the use of synthetic food additives and
of conservation of environment and human safety has cre-
this approach became viral. Green movement was started for
ated fresh enthusiasm to obtain colors from natural sources
the use of natural food additives by activists and their nutri-
because of their non-carcinogenic, biodegradable, and
tional values were highlighted. Because of these activities,
non-toxic nature [4].
nowadays synthetic colors are interpreted as contaminants
Pigmentation is a common attribute of chromogenic
[13].
bacteria and the colors displayed by them are due to light
Two major sources of natural pigments are micro-
absorbing compounds. These pigments produced by the
organisms and plants [14, 15]. The pigments derived from
bacteria act as defensive agents e.g., xanthomonadin pro-
plants possess several drawbacks as compared to pigments
duced by Xanthomonas oryzae protects from photo dam-
from bacteria e.g., instability against adverse pH, heat or
age [5]. The multifunctional nature of bacterial pigments
light, low solubility in water, and are often consistently not
has been demonstrated in various fields e.g., cosmetics,
available. Certain properties make microbial pigments an
food and pharmaceutical industry [6, 7]. To date more than
emerging field of research and of great interest for vari-
50,000 drugs are microbe derived products, mostly from
ous applications. These include availability of cultivation
soil microbes [8]. The emergence of several complicated
technology [16, 17], stability [18], fast and easy growth on
and untreatable anomalies and drug resistance demands the

13
Pigments from Soil Bacteria and Their Therapeutic Properties: A Mini Review

culture media, independence of weather conditions, vari- [10]. Therapeutic applications of soil derived bacterial
ety of shades which are biodegradable and environment- pigments are discussed below.
friendly and most importantly independence of specific
culture conditions e.g., extreme temperature and pH [19]. Anti‑cancer Potential of Soil Bacterial Pigments
Micro-organisms produce pigments with lower residue
and higher fermentation yield as compared to animals Despite the fact that cancer death rates are decreased con-
and plants [20]. Carotenoid production by plants, animals tinuously over the past 2 decades and about 1.7 million
and microbes is taken as an example in this regard. Apart cancer cases were prevented causing an overall drop of
from geographic and seasonal variability, carotenoid syn- 23%, cancer is still one of the leading cause of mortality.
thesis by plants do not possess hazardous waste produc- Continued basic and clinical research is required to fight
tion as in case of chemical synthesis and hence is safe with this fatal disease [73]. Among all the potential anti-
and environment-friendly. On the other hand, carotenoid cancer drugs from natural sources bacterial pigments are
production by microbes ensures more safety and is eco- less assessed in past and trend has been shifted towards
nomical in terms of cost [21]. Some of these carotenoid them with many recent studies in this regard e.g., the anti-
producing bacteria are Rhodobacter sphaeroides [22], tumor property of prodigiosin by S. marcescens [74].
Flavobacterium multivorum [23], Agrobacterium auran- The cytotoxic potency of prodigiosin has been investi-
tiacum, Gordonia jacobea, Paracoccus carotinifaciens gated in the standard 60 cell line panels of human tumor
[24], and Sphingomonas sp. [25]. The safety of natural cells. Inhibition of cell proliferation and induction of cell
dyes cannot be preponderance by its slightly raised cost death has been observed in these cell lines. In vitro anti-
i.e. US$1000/kg for β-carotene as compared to US$500/ cancer activity has also been reported for different prodigi-
kg for synthetic one. osin analogs [10] and its cytotoxic potential against pan-
creatic cancer rises hope for treatment of the most deadly
disease in the USA, killing 30,000 individuals per year
[75]. Violacein, a pigment isolated from C. violaceum, was
Soil Bacterial Pigments reported to cause Human leukemia cell death. Violacein
mediates apoptosis by activating signal transduction TNF
A number of pigments are produced by various type of receptor 1 and represents the novel class of cytotoxic drugs
micro-organisms e.g., carotenoids, melanins, flavins, [76]. Beta carotene, an orange–yellow pigment isolated
quinones, prodigiosins and more specifically monascins, from Rhodococcus maris, reduces the risk of breast can-
violacein, or indigo. Some of the soil bacteria and their cer [10]. Doxorubicin, a red pigment isolated from Strep-
bioactive pigments are shown in Table 1. tomyces peucetius and Streptomyces venezuelae, proved
itself as a promising anti-tumor compound [46, 49]. Beside
these, Deinoxanthin and quinone-anthracycline are unique
red colored bioactive compounds isolated from D. radio-
Therapeutic Applications of Pigments durans and Streptosporangium with strong anti-tumor
Extracted from Soil Bacteria therapeutic potential [35, 54].

One of the leading causes of death is infectious diseases,


responsible for approximately 13.3 billion mortality cases Antileishmanial Potential of Soil Bacterial Pigments
worldwide. Currently, infectious agents are becoming
more resistant to the drugs used against them and are caus- More than 12 million people worldwide are affected by
ing severe life threatening disease. The increase in these Leishmaniasis, the most fatal and disfiguring protozoan dis-
irresistible infectious events cannot be fully explained [48, ease. The drugs used for the treatment of disease are poten-
72]. For the prevention and treatment of these diseases, tially toxic and developed 50 years ago. Violacein extracted
natural sources are constantly evaluated and examined for from C. violaceum showed 10 times less activity than penta-
their potential role. The chemical applications, efficacy midine, which is a second choice drug used in the treatment
and certain properties e.g., anti-fungal, anti-cancer and of leishmaniasis. Although more effective than violacein,
immune suppression of the pigmented bacteria reported so pentamidine is extremely toxic resulting in changes in elec-
far in different studies make them a great area of interest. trocardiogram, renal and hepatic problems [72, 77]. Viola-
Sufficient advancement has been achieved in this field and cein can be a better choice in future for treatment of this life
bioactive compound examination of pigmented bacteria is threatening disease. Currently, other soil bacteria are also
increasing exponentially as the rate of compound isolation evaluated for their antileishmanial potential and discovery
from bacteria is faster as compared to other organisms of novel drugs is expected. Up to date, only one study has

13
R. Mumtaz et al.

Table 1  Pigment producing soil bacteria and their application


Year Soil bacteria Pigment Color Application References

2018 Dyadobacter flavus Flexirubin-type Yellow Skin disease, gastric ulcer [26]
2018 Dyadobacter terricola Flexirubin-type Yellow Skin disease, gastric ulcer [26]
2018 Deinococcus rufus Quinone Red Antimicrobial [27]
2018 Bacillus sp. Squalene Yellowish-orange
Promote plant growth under salt and metal [28]
stress
2017 Neisseria spp. Unknown Red Anti-bacterial activity [29]
2017 Pseudomonas aeruginosa Pyocyanin Blue green Control phytopathogen [30]
2017 Sphingomonas antarctica Unknown Yellow Catalase negative(help the bacteria to survive) [31]
2017 Bacillus megaterium Unknown Orange Anti-bacterial and antioxidant properties [32]
2017 Mucilaginibacter terrae Unknown Red pink Unknown [33]
2017 Microvirga aerilata Unknown Yellow Enzyme production (amylase) [32]
2016 Hymenobacter sp. Carotenoid Red Photosensitizers in dye sensitized solar cells [34]
2016 Chryseobacterium sp. Carotenoid Yellow Photosensitizers in dye sensitized solar cells [34]
2015 Deinococcus radiodurans Deinoxanthin Red Anticancer [35]
2015 Micrococcus luteus Sarcinaxanthin Yellow Unknown [36]
2015 Pseudomonas zhaodongensis Ubiquinone Yellow–orange Cardiovascular disease [37]
2015 Bacillus weihenstephanensis Melanin-like Dark brown Protection against light damage [38]
2014 Streptomyces iakyrus Phenazinomycin Blue Anticancer [39]
2014 Chryseobacterium sp. Flexirubin type Yellowish-orange Chronic skin disease, eczema, gastric ulcers [40]
2014 Chryseobacterium artocarpi Menaquinone Yellow Unknown [41]
2012 Streptomyces sp. Undecylprodigiosin Deep red Anti-bacterial, antioxidative and protection [42]
against photo damage
2012 Chryseobacterium vietnamense Flexirubin type Yellow Skin disease [43]
2012 Streptomyces gramineus Melanin Dark brown Photo protection [44]
2011 Bacillus cereus Azaphenanthrene Green Antimicrobial [45]
2011 Streptomyces venezuelae Doxorubicin Red Anticancer [46]
2011 Streptomyces caeruleatus sp. Unknown Dark blue Anti-bacterial activity [47]
2011 Streptomyces hygroscopicus Sugar molecules Yellow Antimicrobial [48]
2010 Streptomyces peucetius Doxorubicin Red Anticancer [49]
2010 Streptomyces coelicolor Actinorhodin Blue Antibiotics [50]
2009 Streptomyces hygroscopicus Unknown Yellow Anti-bacterial [48]
2009 Kineococcus xinjiangensis sp. Unknown Brown–orange Unknown [51]
2009 Janthinobacterium lividum XT1 Violacein Violet Anticancer, antileishmanial, antibiotic, antivi- [52]
ral, anti-tumoral and anti-Trypanosoma cruzi
activities
2007 Streptomyces vietnamensis Unknown Violet blue Unknown [53]
2006 R. sphaeroides Carotenoid Unknown Precursors of vitamin A, scavengers of active [22]
oxygen, antitumor
2006 Streptosporangium Quinone-anthracycline Red Antimicrobial and anticancer [54]
2004 Sphingomonas sp. β-carotene Orange–yellow Anticancer, cardiovascular and eye disease [25]
2003 Flavobacterium sp. Ant342 Flexirubin Yellow orange Chemotherapy of tuberculosis [55]
2003 Chromobacterium violaceum Violacein Violet Anti-viral and cytotoxic activity [56]
2002 B. megaterium Chlorxanthomycin Yellow–orange Anti-bacterial [57]
2002 Sinorhizobium meliloti Turbomycin A Orange Antibiotic [58]
2002 Sinorhizobium meliloti Turbomycin B Red Antibiotic [58]
2002 Sinorhizobium meliloti Melanin like pigment Dark brown Protection against light damage [58]
2001 Corynebacterium glutamicum Decaprenoxanthin Yellow Protection against photo damage [59]
2001 Gordonia jacobaea Canthaxanthin Reddish-orange Unknown [60]
2000 Brevibacterium linens Carotenoid Yellowish-orange Cheese ripening [61]
1997 Streptomyces aureofaciens Tetracycline Yellow Antibiotic [62]
1996 Streptomyces lividans Actinorhodin Blue Antibiotic [63]

13
Pigments from Soil Bacteria and Their Therapeutic Properties: A Mini Review

Table 1  (continued)
Year Soil bacteria Pigment Color Application References

1995 Arthobacter hyalinus Uroporphyrin III Red Cofactors of various enzymes [64]
1995 Arthrobacter globiformis Riboflavin Yellow Conditioning the growth and the development [65]
in natural ecosystems
1980 Flexibacter elegans Flexirubin Orange Chronic skin disease, eczema, gastric ulcers [66]
1978 Streptomyces echinoruber Rubrolone Purple–red Antibiotic [67]
1973 Arthrobacter oxydans Indigoidine Blue Increased resistance to oxidative stress [68]
1966 Micrococcus roseus Canthaxanthin Reddish-orange Unknown [69]
1960 S. aureofaciens Tetracycline Yellow Antibiotic [70]
1960 Streptomyces psammoticus Tetracycline Yellow Antifungal [71]

been reported on the antileishmanial activity of bacterial for antibiotics. The most important are P. aeruginosa,
pigments. Further research needs to be performed to fully Enterobacteriaceae, and Neisseria gonorrhoeae. Enough
understand the mechanism involved in this activity. drug development is needed to combat them. Among the
natural sources, bacteria produce various type of pigments
Anti‑viral Properties of Soil Bacterial Pigments with anti-bacterial properties e.g., melanins, carotenoids,
flavins, monascins, quinones and violacein [82].
Infectious diseases are causing approximately 20% of the The violet pigment containing deoxyviolacein and viola-
mortality worldwide and 1/3 of these cases are caused by cein produced by soil bacterium, Massilia sp. showed strong
viruses, the prodigious club of microbes [78]. The spread activity against B. subtilis, E. coli and S. aureus making it a
and emergence of these viruses has been accelerated by potential candidate as an antibiotic [83]. The bioactive pig-
rapid air transit, a specific traits of modernization and a ment of Streptomyces hygroscopicus in other study showed
demographic trait, urbanization [79]. Although disease out- activity against VRSA, MRSA, and ESBL cultures of Kleb-
breaks can be controlled and detected by rapid diagnostics, siella sp. and E. coli [48]. Gram negative bacteria such as
long-term strategy for public health is usually vaccine-based Escherichia coli, Pseudomonas spp. were inhibited by red
prevention [80]. To combat this problem of medical com- pigment isolated from Neisseria [29]. The anti-bacterial
munity, natural sources are continuously screened for their activity of the orange pigment of B. megaterium SU15 was
anti-viral potential and many bacterial pigments have been reported against Escherichia coli and Salmonella typhi.
triumphantly announced which halt the viral replication The yellow pigment of Streptomyces hygroscopicus showed
cycle either by altering host cell portion essential for repli- activity against MRSA, VRSA, and ESBL cultures of E. coli
cation of virus or viral components. A remarkable anti-viral and Klebsiella sp. [48]. Prodigiosin, extracted and purified
property of violacein isolated from C. violaceum against from Chromobacterium prodgiosum, were antagonistic to
MA104, Vero, HEp-2 and FRhK-4 cells was reported. A the growth of Bacillus subtilis, Corynebacterium diphthe-
concentration-response relationship was shown by viola- riae and Staphylococcus aureus.
cein as with the increase in concentration, the cytotoxicity
increased gradually [56]. Violacein extracted from Janthino- Anti‑fungal Ability of Soil Bacteria Pigments
bacterium lividum XT1 also showed anti-viral potential [52].
Over the past 2 decades, a number of fatal fungal and fungal
like diseases are reported in both animals and plants that are
Anti‑bacterial Ability of Soil Bacteria Pigments also involved in compromising food security [84]. Tradition-
ally amphotericin B used for the anti-fungal therapy is costly
High prevalence of infectious diseases due to raised fre- and toxic (due to infusion-related events e.g., fevers, rigors,
quency of opportunistic pathogens and development of anti- chills and nephrotoxicity). To overcome these problems,
biotic resistance is a warning for the medical community natural sources (plants and bacteria) are evaluated for their
[81]. Annual mortality rate due to these drug resistant infec- anti-fungal potential. Among the reported pigmented bac-
tions is about 7 lac people worldwide and this is expected to teria with anti-fungal properties, Serratia marcescens and
affect about 10 million people by 2050, if necessary actions Neisseria spp. are studied extensively. The pigment prodigo-
are not taken. A list of 12 bacteria is released by World sin is a tripyrrole forming red pillar box colonies [85], first
Health Organization (WHO) which are considered as great- characterized from Serratia marcescens and was reported
est threat to the health of human because of their resistance to be effective bio control agent against cyclamen’s gray

13
R. Mumtaz et al.

mold. Spore germination was inhibited by the red pigment new microbial sources for pigment production, genetic engi-
extracted and purified from bacteria. A synergistic inhibitory neering for strain improvement, evaluation of therapeutic
effect was observed, when chitinolytic enzymes and prod- potential, and commercialization of the new potential drugs
igosin were applied in combination [86]. Strong activity was to eradicate toxic synthetic ones. There should be more
shown by the red pigment isolated and purified from Neisse- focus on investigating the mechanism of action behind the
ria spp., a soil bacteria, against different fungal species e.g., pharmacological potential of bacterial pigments that will be
Aspergillus spp., Candida spp. and Trichoderma spp. [29]. eventually helpful in designing new strategies for the treat-
ment of lethal anomalies. Future studies must be directed
Immunosuppressive Potential of Soil Bacterial towards the chemical structure of bacterial pigments and the
Pigments structure–function correlation.

Immunosuppressant drugs are a class of drugs that suppress, Compliance with Ethical Standards 
or reduce, the strength of the body’s immune system. Some
of these drugs are used to make the body less likely to reject Conflict of interest  The authors declare that they have no conflict of
interest.
a transplanted organ, such as a liver, heart, or kidney [87].
A number of immunosuppressive drugs have been derived
from natural sources. Nakamura and co-workers reported the
immunosuppressive activity of prodigiosin in 1989 for the
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