BACTERIAL TOXINS AND ITS APPLICATIONS

TABLE OF CONTENTS

ABSTRACT
1.0 INTRODUCTION
2.0 HISTORY
3.0 PREPARATION OF TOXIOD
4.0 BACTERIAL TOXIN
5.0 BACTERIAL TOXINS APPLICATION
6.0 FUTURE PROSPECT OF BACTERIAL TOXINS
7.0 CONCLUSION
8.0 REFERENCES

ABSTARCT
Bacterial toxins are proteins encoded by the bacterial
chromosomal genes, plasmids or phages. They are soluble
substances synthesized by certain bacterial, which have been
recognized as the primary virulence factor for a variety of
pathogenic bacterial. These toxins exhibit different
mechanisms in their course of producing diseases. As a result
of this, toxins have been categorically grouped according to
their modes of action which includes, cell membrane damaging,
protein synthesis inhibition, activating second messenger
pathway, activating the host immune response, and inhibiting
the release of neurotransmiters. These mechanisms are
exploited by bacterial and their toxins. Although these toxins
are pathogenic they have been traditionally converted into non-

toxic and immune stimulating substances known as toxoid. The

preparation of toxoid includes, culturing, filtration,
detoxification, incubation and precipitation. These vaccines
have been proven worthwhile in the treatment of certain
medical disorders and pharmaceutical application.

INTRODUCTION
Bacterial toxins are by-products produced by pathogenic
microbes that have taken up residence in the body. Bacteria
toxins are soluble substances that alter the normal metabolism
of host cells with deleterious effect (Schlessinger and
shaechter,. 1993).several types of bacterial toxins infect the
human body at different sites for instance, enterotoxins are
toxic to proteins generated in the intestines. Neurotoxins
specifically target nerve cells. In addition, certain enzymes may
be produced that can impair metabolic functioning. Common
disease caused by bacterial toxins include, diphtheria,
whooping cough, cholera, anthrax, botulism, tetanus, bloody
diarrhea and heamolytic uremic syndrome. Toxins are now
applied in the treatment of medically important diseases such
as cancer, dystonias, vaginismus, facial wrinkles and other
medical disorders.(Dhakul et al,.2010)
HISTORY
Different types of bacterial toxins have been
identified in past years. Since diphtheria toxin was isolated by
Roux and Yersin in 1888,microbial toxin have been recognized
as the primary virulence factor for a variety of pathogenic
bacteria. Justinus Kerner described botulinum toxin as a
sausage poison and fatty poison because of their mode of
entering. In 1897, Emile Van Ermengem found that the
producer of the botulin toxin was a bacterium which he then
named clostridium botulinum . In 1928, P. Tessmer Snipe and
Hernann Sommer for the first time purified the toxin. In 1949,
Arnold Burgens group also discovered ,through elegant

experiment, that botulinum toxin blocks neuromuscular

transmission through decreased acetylcholine release. In the
late 1960s,Alan Scott, and Edward Schantz were the first to
work on a standardized toxin preparation, In 1973,Scott
experimented the toxin in a monkey. While in1980,Scott
officially used the toxin in human to treat crossed
eyes(Blepharospasm) in 1993,Pasricha proved that the
botulinum toxin could be used for the treatment of achalasia.

PREPARATION OF TOXOIDS
Most licensed toxoid vaccines are relatively crude but effective
(Cherry,.1997),
Traditionally, the steps involved in toxoid preparation includeS.
CULTURING. Since the filtrates contains numerous impurities
and metabolites that may cause heterogenous product,
culturing results in the isolation of purified toxin from the
bacterium in use.
FILTRATON. Using high pressure liquid chromatography can
guarantee 80percent purity of the toxin.
DETOXIFICATION. Here the toxic effect of the toxin is
neutralized.
INCUBATION. The substance in process is incubated at 36 to
42 degree for 28days.To allow for the complete transformation
of the toxin.
PRECIPITATION. The precipitate of the toxoid ranges from 2
to 5 percent.
(Ginnaga et al,.1991). (Homma et al,.1978).

BACTERIAL EXOTOXINS AND ENDOTOXINS.

ENDOTOXIN: These are cell-associated substances that are

structural components of bacteria. Most endotoxins are located
in the cell envelope. It refers to the lipopolysachharide(LPS) or
lipooligosaccharide (LOS) located in the outer membrane of
gram-negative bacterial. Although structural components of
cells. soluble endotoxins may be released from growing
bacteria or from cells that are lysed as a result of effective host
defense mechanisms. Endotoxins generally acts in the vicinity
of bacterial growth or presence. Many bacterial endotoxins are
at first not aggresively toxic as exotoxin due to the cellular
walls of bacteria. Endotoxins can not be used to produce
vaccines, They are also released by gram-negative bacterial.
EXOTOXIN: These are usually secreted by bacteria and acts at
a site removed from bacterial growth. However, in some cases,
exotoxins are only released by lysis of the bacterial cell. They
are usually proteins, minimally polypeptides, that act
enzymatically or through direct action with host cells and
stimulate a variety of host responses. Most exotoxins act at
tissue sites remote from the original point of bacterial invasion
or growth. However, some bacterial exotoxins act at the site of
pathogen colonization and may play a role in invasion.
Exotoxins are produced by both gram-positive and gramnegative bacterial. Some of which are quite poisonous, for
example, tetanus, caused by clostridium tetani that acts as a
neurotoxin. Exotoxin can be used to produce vaccines.
BACTERIAL TOXINS
There are several types of bacterial toxins that may infect the
human body at different sites. Normally, the body attempts to
eliminate bacterial toxins before they can cause harm. The
immune system is the first line of defense but may become
overwhelmed by the rate of bacterial replication. Inflammation
is an indication that bacterial overgrowth is occurring (Smith et
al.,1988).in this case, the immune system will do the next best
thing-move the bacteria out of the way. Usually, fat cells are

the selected storage sites, which can lead to the formation of

cysts and tumors(Sobel .,2005).
COMMON TYPES OF BACTERIAL TOXINS
(1)

Botulinum neurotoxins

(2)

Tetanus toxins

(3)

Vibrio RTX toxins

(4) Staphylococcal toxins

(5) cyanobacteria toxins
(6) mycotoxins
(7) Aflatoxins
(8) Botulinum toxins

BACTERIAL TOXIN APPLICATION

Bacterial toxins have been used as biological tools in
understanding the mechanism of Adenylate cyclase activation
in eukaryotic cells(Harnett et al,.1994). some of the known
applications of bacterial toxins includes:
1. Cancer therapy
2. Dystonias therapy
3. Cosmetology
4. Gynecology
5. Prevention of heart attack
CANCER THERAPY

Toxins can either be used directly or as components of

immunotoxins for the treatment of cancer.( Pastan et al,.1997).
Such cancers include Lymphoma and leukemia. Similarly, the
activities of several potent cytotoxins have been harnessed as
potential therapies for certain cancers. Such toxins can either
be used directly in treatment or as components of immunotoxin
(Ghetie et al,.1997). (Winkler et al,.1988)

FIGURE 1, SCOTT A.B (1980)

DYSTONIAS THERAPY
Dopaminergic agents produced by endotoxins acts on the
dopamine system and the neurotransmitter dopamine, which
helps control muscle movement. GABAergic agents also
regulates the neurotransmitter including the benzodiazepines
such as diazepam and baclofen. Anticholinergic agents

synthesized by endotoxin block the effects of the

neurotransmitter acetylcholine.
COSMETOLOGY
A botox injection, consisting of a small dose of botulinum toxin
can be used to prevent development of wrinkles by paralyzing
facial muscles.
GYNECOLOGY
This involves injecting botulinum toxin, also known as botox
into the wall bladder using local anesthesia. The toxin blocks
the signal or impulses being sent from the nerves to the
bladder muscles, therefore reducing the muscle contraction.

FIGURE 2. FERRACI J,. et al (2005)

PREVENTION OF HEART ATTACK

Another toxic bacterial product with
medical applications is streptokinase, a potent plasminogen
activator produced by several pathogenic streptococcal strains.
The proteolytic activity of streptokinase is used to clear blocked
arteries in patients who have heart attack.
FUTURE PROSPECTS OF BACTERIAL
TOXINS
Development of therapeutics such as small molecule
inhibitors of the enzyme is moving forward.(Breidentach
-Brunger et al,.2005).
CONCLUSION
Microbial toxins capable of interrupting or hyperstimulating many essential functions and pathways of
eukaryotic cells have evolved along with the carrier bacterium.
Evidently, these toxins offer some survival and pathogenic
benefits to the bacterium either during a stage of the host
-parasite interaction or in some environmental niche
encountered by the bacterium. These toxins vary based on
their pathology. Although detrimental to the susceptible host
during an infection, the activities of several toxins have been
exploited as proteins of eukaryotic cellular pathways and for
medical applications.

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