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In recent years, one
of the most interesting research topic is endophyte. Endophyte are the
“microbes that colonize living, internal tissues of plants without causing any
immediate overt negative effects”1.  It’s very familiar to
us that more or less every plant species is expected
to have one or more endophyte species2,3.Endophytic microorganisms include fungi and
bacteria. After entering the host, endophytes reside within
intracellular or the intercellular spaces or in the vascular tissues of host plant4. After gaining
residence in the plant tissues, the endophytes are known to produce a diverse
range of natural products which could be consistent and successful source of drugs. .

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After the discovery of taxol produced by
endophytic fungus Taxomyces andreanae from Taxus brevifolia researchers
have been motivated to evaluate the potentiality
of these microorganisms in the production of
bioactive compounds5. Endophytes
provide a broad variety of bioactive secondary metabolites, including
alkaloids, benzopyranones, chinones, flavonoids, phenolic acids, quinones,
steroids, terpenoids, tetralones, xanthones, and others6. Endophytes have the potentiality to produce different bioactive
metabolites which play an important role in antimicrobial, anticancer and other
pharmaceutical activity7,8.Such bioactive metabolites from endophytes find
wide-ranging application as antimicrobials, agrochemicals, antibiotics, immunosuppressants,
antiparasitics, antioxidants, and anticanceragents9.


This review focuses particularly on bacterial
endophytes as a potential source of novel antibiotics.



endophytes are colonise mainly intercellularly10,11, though they have also been found
intracellularly, e.g. Azoarcus sp.12. 
Bacteria are also frequently found in the vascular tissues of host



Endophytes present within the host plant including
herbaceous to   angiosperm plant.  Endophytes are isolated from their host plant
growing in tropical,temperate & boreal forests14. Endophytes are found in various habitat
including extreme arctic,alpine,xeric environment 6and also found in mesic,temperate and
tropical forests 14. . Endophytes have been present within their
hosts ranging from mosses, ferns, gymnosperms and angiosperms6.
Endophytes have been also recorded inclusion of marine algae and grasses,
mosses and ferns15.
species of cultivable endophytic bacteria (including both gram?positive
and gram?negative)
have been isolated, identified and reported from a large diverse terrestrial
and aquatic plants16.Endophytes are
present in all parts of a given plant host, and some are seed-borne17.Endophytes can
be transferred from plant to plant via seeds 18.



Endophytes have adapted themselves by genetic
variation in the microenvironments 19.Genetic variation is done by uptake of some
plant DNA into their own genomes 19.DNA is transferred by 2 transmission mode,
1)Vertical Transmission20 & 2) Horizontal Transmission20.




Metabolites showing antibiotic activity
can be defined as low-molecular-weight organic natural substances produced by
microorganisms that are active at low concentrations against other
microorganisms 21. Endophytes
play a major role in resistance mechanism to overcome pathogenic invasion by
synthesising secondary metabolites22. So far, studies
reported a large number of antimicrobial compounds isolated from endophytes,
belonging to several structural classes like alkaloids, peptides, steroids,
terpenoids, phenols, quinines, and flavonoids23.

metabolites, such as phytohormones6 and salicylic acid24are frequently isolated from
endophytic bacteria. An endophytic fluorescent bacterium Pseudomonas
viridiflava associated with leaves of many grass species produces a group
of novel antifungal lipopeptides named ecomycins, which contain some unusual
amino acids such as homoserine and b-hydroxyaspartic acid25. Methylobacterium extorquens
and Pseudomanas synxantha are two endophytic bacteria from
meristematic bud tissues of the Scots pine (Pinus sylvestris L.).
They are found to produce adenine derivatives which may have a role as
precursors in cytokinin biosynthesis6.



Now days ecosystems are deteriorating very rapidly thus a variety of
new types of health issues are arising within the human population. For this
remediation, it’s necessary to find out new types of antibiotics through
research. Antibiotics and other anti-microbial natural compounds should become
the research of concern.

According to Webster’s English
Dictionary, an antibiotic is defined as “a substance produced by a
microorganism and able, in dilute solution, to inhibit or kill another
microorganism.”. Thomashow et al. defined the antibiotics in a new way, i.e. , “antibiotics
encompass a chemically heterogeneous group of organic, low-molecular weight
compounds produced by microorganisms that are deleterious to the growth or
metabolic activities of other microorganisms”26. Antibiotics
generally play several vital roles in microbes against their cell wall
biosynthesis and DNA, RNA, and protein synthesis. Davies27 proposed that “in
the beginnings of biochemical evolution antibiotic like molecules probably
played an important role as effectors or as catalysts in a variety of
condensation reactions such as transcription and translation”. He further
postulated that “by the time these molecules retained their ability to interact
with the receptor sites in nucleic acids and proteins, thereby conferring their
activity as antibiotics”. Thus, endophytic bacteria comprise of diverse genera
that produce complex bioactive molecules play an important role in antibiotic




The discovery of antibiotics from
endophytic bacteria include the ecomycins from the known grass endophytic
bacterium,  Pseudomonas viridiflava25.
This endophyte is one of the plant?associated fluorescent Pseudomonads;
and it is known to exist in the tissues of many grass species. The identified
and partially characterized three antifungal lipopeptides produced by P.
viridiflava strain EB273 are called as Ecomycin A, B and C. The Ecomycins represent
a family of novel lipopeptides and are made up of some unusual amino acids
including homoserine and ??hydroxy aspartic acid.
Out of these three molecules, the Ecomycin A is similar to (amino acid composition)
an already reported antibiotic syringotoxin28. However,
based on the molecular weight and amino acid compositional data, ecomycins B
and C represent a unique set of related lipopeptides not possessing
phenylalanine, lysine, arginine, ornithine or diaminobutyric acid, which are
constituents of such compounds as the pseudomycins, syringomycins,
syringostatins and syringotoxin28,29,30.
Each ecomycin contained ? -hydroxy aspartic acid, threonine, serine,
homoserine, glycine, alanine and an unknown amino acid and with one exception
(syringotoxin) distinguishes them from all other antifungal lipopeptides.
However, ecomycins A and B yielded significant level of alanine. Ecomycin A was
the only member of the family containing 2,4-diaminobutyric acid and ornithine.
Ecomycin C had a level of alanine similar to that of ecomycin A25.




The Pseudomycins represent a group of
peptide antifungal compounds isolated from liquid cultures of Pseudomonas
syringae, a plant?associated bacterium. The P. syringae
is a member of the Pseudomonadaceae family of Proteobacteria phylum. These
antifungal peptide are mainly lipopeptides containing aminoacids like L?chlorothreonine,
aspartic acid and both D?and L?diaminobutyric acid. There
are four types of pseudomycins, pseudomycins A?D, have effective
activity against the human pathogen, Candida albicans, C. neoformans.
Pseudomycins A?C
contain hydroxyaspartic acid, serine, arginine, lysine and diaminobutyric acid.
Pseudomycin D, on the other hand, has a molecular mass of 2401Da and is more
complex than pseudomycins A?C31.




The munumbicins were isolated from a Streptomyces
NRRL 30562 that colonizes snakevine (Kennedia nigriscans), a plant
species that was used to prevent wound sepsis. Munumbicins A, B, C and D are
newly described antibiotics with a wide spectrum of activity against plant
pathogenic fungi and bacteria, and a Plasmodium species. The munumbicins
act against Gram?positive bacteria such as Bacillus
anthracis, Streptococcus pneumoniae, Enterococcus faecalis and
Staphylococcus aureus.32.The
interesting fact is that, the methicillin?resistant strain of S.aureus
(MRSA, ATCC 33591) and a vancomycin?resistant strain of E.
faecalis (VREF, ATCC 51299) are two of the Gram?positive
bacterial strains that are commonly drug?resistant. The munumbin
B is effective against multiple?drug?resistant
(MDR) Mycobacterium tuberculosis, an acid?fast bacterium. The
munumbicins C and D are of a special interest because in addition to being
effective against Gram positive and negative bacteria, they are effective
against the malarial parasite  Plasmodium
falciparum. The munumbicin D was reported as more powerful than
chloroquine, the gold?standard antimalarial drug. Munumbicins
B, C and D compounds are not effective against human pathogenic fungi33. Each
of the four munumbicins compounds consists with the presence of Glx (glutamic
acid or glutamine), Pro, Thr and Val, except for munumbicin C, which had an
extra proline32.




Kakadumycins produced (in culture)
by endophytic bacterium Streptomyces (NRRL30566) from a fern?leaved
Grevillea tree (Grevillea pteridifolia, Synonym: Grevillea
chrysodendron R.Br.) native to the northern territory of Australia.
Kakadumycin A, has antibacterial activity similar to Munumbicins; and it is
also effective against P. falciparum. Kakadumycin A is chemically
related to echinomycin, another Streptomyces derived quinoxaline
antibiotic, a potential anticancer drug34.




The Xiamycins represent one of the
indolosesquiterpenes isolated from prokaryotes. There are 2 types of xiamycins,
one is Xiamycin a which is a pentacyclicindolosesquiterpene and another one is
xiamycin b that is a indolosesquiterpenes. Along with this two type of
xiamycins other two new type of indolosesquiterpenes isolated from the culture
broth of Streptomyces sp. strain HKI0595, a bacterial endophyte of the
widespread mangrove tree,

Kandelia candel has
been reported by Ding et al. Their research findings suggest that these
Xiamycins do have moderate to strong antimicrobial activities against several
bacteria, including methicillin?resistant Staphylococcus
aureus and vancomycin?resistant Enterococcus faecalis35.
Interestingly, Xiamycin?A also exhibits selective anti?HIV




Another interesting discovery was
oocydin A, a chlorinated macrocyclic lactone produced by Serratia marcescens
living inside the aquatic plant species Rhyncholacis penicillata37.
Strobel et al. speculated that oocydin A may contribute to the natural
protection of R. penicillata against oomycete pathogens that are
prevalent in the aquatic environment38.



Antifungal activity is also shown by the
endophytic bacteria, Paenibacillus
polymyxa associated with Wheat plant by producing Fusaricidin A–D active
compound39. Coronamycin
produced by a verticillate Streptomyces
sp. isolated as an endophyte from an epiphytic vine, Monstera sp., found in the Manu region of the upper Amazon of Peru
shows antimalarial, antifungal activity against pythiaceous fungi and the human
fungal pathogen Cryptococcus neoformans40.




The objective of this
paper was to review the diversity of secondary metabolites with anti-microbial
activities produced by endophytic bacteria. This review covered 8 antibioticss
with diverse activities against plant pathogens, produced from different kinds
of endophyteic bacteria inhabiting from a range of plant species. This review
is suggesting that as bacterial endophytes are potentially vital sources for
antibiotics thus significant numbers of antibiotics remain to be discovered
from less explored or unexplored endophytic bacteria.





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