Clostridium Botulinum
   HOME

TheInfoList



OR:

''Clostridium botulinum'' is a
Gram The gram (originally gramme; SI unit symbol g) is a Physical unit, unit of mass in the International System of Units (SI) equal to one one thousandth of a kilogram. Originally defined as of 1795 as "the absolute weight of a volume of pure wate ...
-positive,
rod-shaped A bacillus (), also called a bacilliform bacterium or often just a rod (when the context makes the sense clear), is a rod-shaped bacterium or archaeon. Bacilli are found in many different taxonomic groups of bacteria. However, the name '' Baci ...
,
anaerobic Anaerobic means "living, active, occurring, or existing in the absence of free oxygen", as opposed to aerobic which means "living, active, or occurring only in the presence of oxygen." Anaerobic may also refer to: * Anaerobic adhesive, a bonding a ...
, spore-forming,
motile Motility is the ability of an organism to move independently, using metabolic energy. Definitions Motility, the ability of an organism to move independently, using metabolic energy, can be contrasted with sessility, the state of organisms th ...
bacterium Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
with the ability to produce the
neurotoxin Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insultsSpencer 2000 that can adversely affect function in both developing and mature ner ...
botulinum Botulinum toxin, or botulinum neurotoxin (BoNT), is a neurotoxic protein produced by the bacterium ''Clostridium botulinum'' and related species. It prevents the release of the neurotransmitter acetylcholine from axon endings at the neuromusc ...
. The botulinum toxin can cause
botulism Botulism is a rare and potentially fatal illness caused by a toxin produced by the bacterium ''Clostridium botulinum''. The disease begins with weakness, blurred vision, feeling tired, and trouble speaking. This may then be followed by weakne ...
, a severe flaccid paralytic disease in humans and other animals, and is the most potent toxin known to mankind, natural or synthetic, with a lethal dose of 1.3–2.1 ng/kg in humans.(2010). Chapter 19. ''Clostridium'', ''Peptostreptococcus'', ''Bacteroides'', and Other Anaerobes. In Ryan K.J., Ray C (Eds), ''Sherris Medical Microbiology'', 5th ed. ''C. botulinum'' is a diverse group of
pathogenic bacteria Pathogenic bacteria are bacteria that can cause disease. This article focuses on the bacteria that are pathogenic to humans. Most species of bacteria are harmless and are often Probiotic, beneficial but others can cause infectious diseases. The n ...
initially grouped together by their ability to produce botulinum toxin and now known as four distinct groups, ''C. botulinum'' groups I–IV, as well as some strains of ''Clostridium butyricum'' and ''Clostridium baratii'', are the bacteria responsible for producing botulinum toxin. ''C. botulinum'' is responsible for foodborne
botulism Botulism is a rare and potentially fatal illness caused by a toxin produced by the bacterium ''Clostridium botulinum''. The disease begins with weakness, blurred vision, feeling tired, and trouble speaking. This may then be followed by weakne ...
(ingestion of preformed toxin), infant botulism (intestinal infection with toxin-forming ''C. botulinum''), and wound botulism (infection of a wound with ''C. botulinum''). ''C. botulinum'' produces heat-resistant
endospore An endospore is a dormant, tough, and non-reproductive structure produced by some bacteria in the phylum Bacillota. The name "endospore" is suggestive of a spore or seed-like form (''endo'' means 'within'), but it is not a true spore (i.e., no ...
s that are commonly found in soil and are able to survive under adverse conditions. ''C. botulinum'' is commonly associated with bulging canned food; bulging, misshapen cans can be due to an internal increase in pressure caused by gas produced by bacteria.


Microbiology

''C. botulinum ''is a
Gram-positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bacte ...
, rod-shaped, spore-forming
bacterium Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
. It is an
obligate anaerobe Obligate anaerobes are microorganisms killed by normal atmospheric concentrations of oxygen (20.95% O2). Oxygen tolerance varies between species, with some species capable of surviving in up to 8% oxygen, while others lose viability in environm ...
, meaning that
oxygen Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as wel ...
is poisonous to the cells. However, ''C. botulinum'' tolerates traces of oxygen due to the enzyme superoxide dismutase, which is an important antioxidant defense in nearly all cells exposed to oxygen. ''C. botulinum'' is able to produce the neurotoxin only during sporulation, which can happen only in an anaerobic environment. ''C. botulinum'' is divided into four distinct
phenotypic In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...
groups (I-IV) and is also classified into seven
serotype A serotype or serovar is a distinct variation within a species of bacteria or virus or among immune cells of different individuals. These microorganisms, viruses, or cells are classified together based on their surface antigens, allowing the epi ...
s (A–G) based on the antigenicity of the botulinum toxin produced.


Groups

Physiological differences and genome sequencing at 16S
rRNA Ribosomal ribonucleic acid (rRNA) is a type of non-coding RNA which is the primary component of ribosomes, essential to all cells. rRNA is a ribozyme which carries out protein synthesis in ribosomes. Ribosomal RNA is transcribed from ribosoma ...
level support the subdivision of the ''C. botulinum'' species into groups I-IV. One of the fundamental differences between group I and group II is that ''C. botulinum'' group I can lyse native proteins like coagulated egg white, cooked meat particles, whereas group II cannot. However, group II can ferment various carbohydrates like
sucrose Sucrose, a disaccharide, is a sugar composed of glucose and fructose subunits. It is produced naturally in plants and is the main constituent of white sugar. It has the molecular formula . For human consumption, sucrose is extracted and refined ...
and
mannose Mannose is a sugar monomer of the aldohexose series of carbohydrates. It is a C-2 epimer of glucose. Mannose is important in human metabolism, especially in the glycosylation of certain proteins. Several congenital disorders of glycosylation ...
, and both of them can degrade the derived protein, gelatin. Human
botulism Botulism is a rare and potentially fatal illness caused by a toxin produced by the bacterium ''Clostridium botulinum''. The disease begins with weakness, blurred vision, feeling tired, and trouble speaking. This may then be followed by weakne ...
is predominantly caused by group I or II ''C. botulinum''. Group III organisms mainly cause diseases in non-human animals. Group IV ''C. botulinum'' has not been shown to cause human or animal disease.


Botulinum toxin

Neurotoxin Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insultsSpencer 2000 that can adversely affect function in both developing and mature ner ...
production is the unifying feature of the species. Eight types of
toxins A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organisms. Toxins occur especially as a protein or conjugated protein. The term toxin was first used by organic chemist Ludwig Brieger (1849–1 ...
have been identified that are allocated a letter (A–H), several of which can cause disease in humans. They are resistant to degradation by enzymes found in the gastrointestinal tract. This allows for ingested toxins to be absorbed from the intestines into the bloodstream. However, all types of botulinum toxin are rapidly destroyed by heating to 100 °C for 15 minutes (900 seconds). Botulinum toxin, one of the most poisonous biological substances known, is a neurotoxin produced by the bacterium ''Clostridium botulinum''. ''C. botulinum'' elaborates eight antigenically distinguishable exotoxins (A, B, C1, C2, D, E, F and G). Most strains produce one type of
neurotoxin Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insultsSpencer 2000 that can adversely affect function in both developing and mature ner ...
, but strains producing multiple toxins have been described. ''C. botulinum'' producing B and F toxin types have been isolated from human botulism cases in
New Mexico ) , population_demonym = New Mexican ( es, Neomexicano, Neomejicano, Nuevo Mexicano) , seat = Santa Fe , LargestCity = Albuquerque , LargestMetro = Tiguex , OfficialLang = None , Languages = English, Spanish ( New Mexican), Navajo, Ker ...
and
California California is a U.S. state, state in the Western United States, located along the West Coast of the United States, Pacific Coast. With nearly 39.2million residents across a total area of approximately , it is the List of states and territori ...
. The toxin type has been designated Bf as the type B toxin was found in excess to the type F. Similarly, strains producing Ab and Af toxins have been reported. Evidence indicates the neurotoxin genes have been the subject of
horizontal gene transfer Horizontal gene transfer (HGT) or lateral gene transfer (LGT) is the movement of genetic material between Unicellular organism, unicellular and/or multicellular organisms other than by the ("vertical") transmission of DNA from parent to offsprin ...
, possibly from a viral (
bacteriophage A bacteriophage (), also known informally as a ''phage'' (), is a duplodnaviria virus that infects and replicates within bacteria and archaea. The term was derived from "bacteria" and the Greek φαγεῖν ('), meaning "to devour". Bacteri ...
) source. This theory is supported by the presence of integration sites flanking the toxin in some strains of ''C. botulinum''. However, these integrations sites are degraded (except for the C and D types), indicating that the ''C. botulinum'' acquired the toxin genes quite far in the evolutionary past. Nevertheless, further transfers still happen via the plasmids and other mobile elements the genes are located on.


Botulinum toxin types

Only botulinum toxin types A, B, E, F and H cause disease in humans. Types A, B, and E are associated with food-borne illness, while type E is specifically associated with fish products. Type C produces limber-neck in birds and type D causes botulism in other mammals. No disease is associated with type G. The "gold standard" for determining toxin type is a mouse bioassay, but the genes for types A, B, E, and F can now be readily differentiated using
quantitative PCR A real-time polymerase chain reaction (real-time PCR, or qPCR) is a laboratory technique of molecular biology based on the polymerase chain reaction (PCR). It monitors the amplification of a targeted DNA molecule during the PCR (i.e., in real ...
. As no antitoxin to type H is yet available, discovered in 2013 and by far the deadliest, details are kept under shroud. A few strains from organisms genetically identified as other ''Clostridium'' species have caused human botulism: ''C. butyricum'' has produced type E toxin and ''C. baratii'' had produced type F toxin. The ability of ''C. botulinum'' to naturally transfer neurotoxin genes to other clostridia is concerning, especially in the
food industry The food industry is a complex, global network of diverse businesses that supplies most of the food consumed by the world's population. The food industry today has become highly diversified, with manufacturing ranging from small, traditiona ...
, where preservation systems are designed to destroy or inhibit only ''C. botulinum'' but not other ''Clostridium'' species.


Laboratory isolation

In the laboratory, ''C. botulinum'' is usually isolated in tryptose sulfite
cycloserine Cycloserine, sold under the brand name Seromycin, is a GABA transaminase inhibitor and an antibiotic, used to treat tuberculosis. Specifically it is used, along with other antituberculosis medications, for active drug resistant tuberculosis. It ...
(TSC) growth medium in an anaerobic environment with less than 2% oxygen. This can be achieved by several commercial kits that use a chemical reaction to replace O2 with CO2. ''C. botulinum'' is a
lipase Lipase ( ) is a family of enzymes that catalyzes the hydrolysis of fats. Some lipases display broad substrate scope including esters of cholesterol, phospholipids, and of lipid-soluble vitamins and sphingomyelinases; however, these are usually tr ...
-positive microorganism that grows between pH of 4.8 and 7.0 and cannot use
lactose Lactose is a disaccharide sugar synthesized by galactose and glucose subunits and has the molecular formula C12H22O11. Lactose makes up around 2–8% of milk (by mass). The name comes from ' (gen. '), the Latin word for milk, plus the suffix '' - ...
as a primary carbon source, characteristics important for biochemical identification.


Taxonomy history

''C. botulinum'' was first recognized and isolated in 1895 by Emile van Ermengem from home-cured
ham Ham is pork from a leg cut of pork, cut that has been food preservation, preserved by wet or dry Curing (food preservation), curing, with or without smoking (cooking), smoking."Bacon: Bacon and Ham Curing" in ''Chambers's Encyclopædia''. Lo ...
implicated in a botulism outbreak. The isolate was originally named ''Bacillus botulinus'', after the Latin word for sausage, ''botulus''. ("Sausage poisoning" was a common problem in 18th- and 19th-century Germany, and was most likely caused by botulism.) However, isolates from subsequent outbreaks were always found to be
anaerobic Anaerobic means "living, active, occurring, or existing in the absence of free oxygen", as opposed to aerobic which means "living, active, or occurring only in the presence of oxygen." Anaerobic may also refer to: * Anaerobic adhesive, a bonding a ...
spore formers, so Ida A. Bengtson proposed that the organism be placed into the genus ''Clostridium'', as the genus ''
Bacillus ''Bacillus'' (Latin "stick") is a genus of Gram-positive, rod-shaped bacteria, a member of the phylum '' Bacillota'', with 266 named species. The term is also used to describe the shape (rod) of other so-shaped bacteria; and the plural ''Bacill ...
'' was restricted to
aerobic Aerobic means "requiring air," in which "air" usually means oxygen. Aerobic may also refer to * Aerobic exercise, prolonged exercise of moderate intensity * Aerobics, a form of aerobic exercise * Aerobic respiration, the aerobic process of cel ...
spore-forming rods. Since 1959, all species producing the botulinum neurotoxins (types A–G) have been designated ''C. botulinum''. Substantial phenotypic and
genotypic The genotype of an organism is its complete set of genetic material. Genotype can also be used to refer to the alleles or variants an individual carries in a particular gene or genetic location. The number of alleles an individual can have in a ...
evidence exists to demonstrate
heterogeneity Homogeneity and heterogeneity are concepts often used in the sciences and statistics relating to the uniformity of a substance or organism. A material or image that is homogeneous is uniform in composition or character (i.e. color, shape, siz ...
within the
species In biology, a species is the basic unit of classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of the appropriate s ...
. This has led to the reclassification of ''C. botulinum'' type G strains as a new species, ''C. argentinense''. Group I ''C. botulinum'' strains that do not produce a botulin toxin are referred to as '' C. sporogenes''. The complete genome of ''C. botulinum'' has been sequenced at
Wellcome Trust Sanger Institute The Wellcome Sanger Institute, previously known as The Sanger Centre and Wellcome Trust Sanger Institute, is a non-profit British genomics and genetics research institute, primarily funded by the Wellcome Trust. It is located on the Wellcome G ...
in 2007.


Pathology


Foodborne botulism

"Signs and symptoms of foodborne botulism typically begin between 18 and 36 hours after the toxin gets into your body, but can range from a few hours to several days, depending on the amount of toxin ingested." * Double vision * Blurred vision * Dropping eyelids * Nausea, vomiting, and abdominal cramps * Slurred speech * Trouble breathing * Difficulty in swallowing * Dry mouth * Muscle weakness * Constipation * Reduced or absent deep tendon reactions, such as in the knee


Wound botulism

Most people who develop wound botulism inject drugs several times a day, so it is difficult to determine how long it takes for signs and symptoms to develop after the toxin enters the body. Most common in people who inject black tar heroin, wound botulism signs and symptoms include: * Difficulty swallowing or speaking * Facial weakness on both sides of the face * Blurred or double vision * Dropping eyelids * Trouble breathing * Paralysis


Infant botulism

If infant botulism is related to food, such as honey, problems generally begin within 18 to 36 hours after the toxin enters the baby's body. Signs and symptoms include: * Constipation (often the first sign) * Floppy movements due to muscle weakness and trouble controlling the head * Weak cry * Irritability * Drooling * Dropping eyelids * Tiredness * Difficulty sucking or feeding * Paralysis


Beneficial effects of botulinum toxin

Purified botulinum toxin is diluted by a physician for treatment: * Congenital pelvic tilt * Spasmodic dysphasia (the inability of the muscles of the larynx) * Achalasia (esophageal stricture) * Strabismus (crossed eyes) * Paralysis of the facial muscles * Failure of the cervix * Blinking frequently * Anti-cancer drug delivery


Adult intestinal toxemia

A very rare form of botulism that occurs by the same route as infant botulism but is among adults. Occurs rarely and sporadically. Signs and symptoms include: * Abdominal pain * Blurred vision * Diarrhea *
Dysarthria Dysarthria is a speech sound disorder resulting from neurological injury of the motor component of the motor–speech system and is characterized by poor articulation of phonemes. In other words, it is a condition in which problems effectively ...
* Imbalance * Weakness in arms and hand area


''C. botulinum'' in different geographical locations

A number of
quantitative Quantitative may refer to: * Quantitative research, scientific investigation of quantitative properties * Quantitative analysis (disambiguation) * Quantitative verse, a metrical system in poetry * Statistics, also known as quantitative analysis ...
surveys for ''C. botulinum''
spores In biology, a spore is a unit of sexual or asexual reproduction that may be adapted for dispersal and for survival, often for extended periods of time, in unfavourable conditions. Spores form part of the life cycles of many plants, algae, f ...
in the environment have suggested a prevalence of specific toxin types in given geographic areas, which remain unexplained.


North America

Type A ''C. botulinum'' predominates the
soil Soil, also commonly referred to as earth or dirt, is a mixture of organic matter, minerals, gases, liquids, and organisms that together support life. Some scientific definitions distinguish ''dirt'' from ''soil'' by restricting the former te ...
samples from the western regions, while type B is the major type found in eastern areas. The type-B organisms were of the proteolytic type I.
Sediments Sediment is a naturally occurring material that is broken down by processes of weathering and erosion, and is subsequently transported by the action of wind, water, or ice or by the force of gravity acting on the particles. For example, sand a ...
from the Great Lakes region were surveyed after outbreaks of botulism among commercially reared
fish Fish are aquatic, craniate, gill-bearing animals that lack limbs with digits. Included in this definition are the living hagfish, lampreys, and cartilaginous and bony fish as well as various extinct related groups. Approximately 95% of li ...
, and only type E spores were detected. In a survey, type-A strains were isolated from soils that were
neutral Neutral or neutrality may refer to: Mathematics and natural science Biology * Neutral organisms, in ecology, those that obey the unified neutral theory of biodiversity Chemistry and physics * Neutralization (chemistry), a chemical reaction in ...
to
alkaline In chemistry, an alkali (; from ar, القلوي, al-qaly, lit=ashes of the saltwort) is a base (chemistry), basic, ionic compound, ionic salt (chemistry), salt of an alkali metal or an alkaline earth metal. An alkali can also be defined as ...
(average pH 7.5), while type-B strains were isolated from slightly
acidic In computer science, ACID ( atomicity, consistency, isolation, durability) is a set of properties of database transactions intended to guarantee data validity despite errors, power failures, and other mishaps. In the context of databases, a sequ ...
soils (average pH 6.23).


Europe

''C. botulinum'' type E is prevalent in aquatic sediments in Norway and Sweden, Denmark, the Netherlands, the Baltic coast of Poland, and Russia. The type-E ''C. botulinum'' was suggested to be a true aquatic organism, which was indicated by the correlation between the level of type-E contamination and flooding of the land with seawater. As the land dried, the level of type E decreased and type B became dominant. In soil and sediment from the United Kingdom, ''C. botulinum'' type B predominates. In general, the incidence is usually lower in soil than in
sediment Sediment is a naturally occurring material that is broken down by processes of weathering and erosion, and is subsequently transported by the action of wind, water, or ice or by the force of gravity acting on the particles. For example, sand an ...
. In Italy, a survey conducted in the vicinity of
Rome , established_title = Founded , established_date = 753 BC , founder = King Romulus (legendary) , image_map = Map of comune of Rome (metropolitan city of Capital Rome, region Lazio, Italy).svg , map_caption ...
found a low level of contamination; all strains were proteolytic ''C. botulinum'' types A or B.


Australia

''C. botulinum'' type A was found to be present in soil samples from mountain areas of
Victoria Victoria most commonly refers to: * Victoria (Australia), a state of the Commonwealth of Australia * Victoria, British Columbia, provincial capital of British Columbia, Canada * Victoria (mythology), Roman goddess of Victory * Victoria, Seychelle ...
. Type-B organisms were detected in marine mud from
Tasmania ) , nickname = , image_map = Tasmania in Australia.svg , map_caption = Location of Tasmania in AustraliaCoordinates: , subdivision_type = Country , subdi ...
. Type-A ''C. botulinum'' has been found in
Sydney Sydney ( ) is the capital city of the state of New South Wales, and the most populous city in both Australia and Oceania. Located on Australia's east coast, the metropolis surrounds Sydney Harbour and extends about towards the Blue Mountain ...
suburbs and types A and B were isolated from
urban Urban means "related to a city". In that sense, the term may refer to: * Urban area, geographical area distinct from rural areas * Urban culture, the culture of towns and cities Urban may also refer to: General * Urban (name), a list of people ...
areas. In a well-defined area of the Darling-Downs region of
Queensland ) , nickname = Sunshine State , image_map = Queensland in Australia.svg , map_caption = Location of Queensland in Australia , subdivision_type = Country , subdivision_name = Australia , established_title = Before federation , established_ ...
, a study showed the prevalence and persistence of ''C. botulinum'' type B after many cases of botulism in
horse The horse (''Equus ferus caballus'') is a domesticated, one-toed, hoofed mammal. It belongs to the taxonomic family Equidae and is one of two extant subspecies of ''Equus ferus''. The horse has evolved over the past 45 to 55 million y ...
s.


Use and detection

''C. botulinum'' is used to prepare the medicaments
Botox Botulinum toxin, or botulinum neurotoxin (BoNT), is a neurotoxic protein produced by the bacterium '' Clostridium botulinum'' and related species. It prevents the release of the neurotransmitter acetylcholine from axon endings at the neuromus ...
, Dysport, Xeomin, and Neurobloc used to selectively paralyze muscles to temporarily relieve muscle function. It has other "
off-label Off-label use is the use of pharmaceutical drugs for an unapproved indication or in an unapproved age group, dosage, or route of administration. Both prescription drugs and over-the-counter drugs (OTCs) can be used in off-label ways, although ...
" medical purposes, such as treating severe facial pain, such as that caused by
trigeminal neuralgia Trigeminal neuralgia (TN or TGN), also called Fothergill disease, tic douloureux, or trifacial neuralgia is a long-term pain disorder that affects the trigeminal nerve, the nerve responsible for sensation in the face and motor functions such as ...
. Botulinum toxin produced by ''C. botulinum'' is often believed to be a potential
bioweapon A biological agent (also called bio-agent, biological threat agent, biological warfare agent, biological weapon, or bioweapon) is a bacterium, virus, protozoan, parasite, fungus, or toxin that can be used purposefully as a weapon in bioterrorism ...
as it is so potent that it takes about 75
nanogram To help compare different orders of magnitude, the following lists describe various mass levels between 10−59  kg and 1052 kg. The least massive thing listed here is a graviton, and the most massive thing is the observable universe ...
s to kill a person ( of 1 ng/kg, assuming an average person weighs ~75 kg); 1 kilogram of it would be enough to kill the entire human population. For comparative purposes, a quarter of a typical grain of sand's weight (350 ng) of botulinum toxin would constitute a lethal dose for humans. A "mouse protection" or "mouse bioassay" test determines the type of ''C. botulinum'' toxin present using
monoclonal antibodies A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ca ...
. An enzyme-linked immunosorbent assay (
ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presence ...
) with
digoxigenin Digoxigenin (DIG) is a steroid found exclusively in the flowers and leaves of the plants '' Digitalis purpurea'', '' Digitalis orientalis'' and '' Digitalis lanata'' (foxgloves), where it is attached to sugars, to form the glycosides (e.g. Lana ...
-labeled antibodies can also be used to detect the toxin, and
quantitative PCR A real-time polymerase chain reaction (real-time PCR, or qPCR) is a laboratory technique of molecular biology based on the polymerase chain reaction (PCR). It monitors the amplification of a targeted DNA molecule during the PCR (i.e., in real ...
can detect the toxin genes in the organism.


Growth conditions and prevention

''C. botulinum'' is a soil bacterium. The spores can survive in most environments and are very hard to kill. They can survive the temperature of boiling water at sea level, thus many foods are canned with a pressurized boil that achieves even higher temperatures, sufficient to kill the spores. This bacteria is widely distributed in nature and can be assumed to be present on all food surfaces. Its optimum growth temperature is within the
mesophilic A mesophile is an organism that grows best in moderate temperature, neither too hot nor too cold, with an optimum growth range from . The optimum growth temperature for these organisms is 37°C. The term is mainly applied to microorganisms. Organi ...
range. In spore form, it is a heat resistant pathogen that can survive in low acid foods and grow to produce toxins. The toxin attacks the nervous system and will kill an adult at a dose of around 75 ng. This toxin is detoxified by holding food at 100 °C for 10 minutes. Botulism poisoning can occur due to preserved or home-canned, low-acid food that was not processed using correct preservation times and/or pressure. Growth of the bacterium can be prevented by high
acidity In computer science, ACID ( atomicity, consistency, isolation, durability) is a set of properties of database transactions intended to guarantee data validity despite errors, power failures, and other mishaps. In the context of databases, a sequ ...
, high ratio of dissolved
sugar Sugar is the generic name for sweet-tasting, soluble carbohydrates, many of which are used in food. Simple sugars, also called monosaccharides, include glucose, fructose, and galactose. Compound sugars, also called disaccharides or double ...
, high levels of oxygen, very low levels of moisture, or storage at temperatures below 3 °C (38 °F) for type A. For example, in a low-acid, canned vegetable such as
green bean Green beans are young, unripe fruits of various cultivars of the common bean ('' Phaseolus vulgaris''), although immature or young pods of the runner bean (''Phaseolus coccineus''), yardlong bean ( ''Vigna unguiculata'' subsp. ''sesquipedalis ...
s that are not heated enough to kill the spores (i.e., a pressurized environment) may provide an oxygen-free medium for the spores to grow and produce the toxin. However, pickles are sufficiently acidic to prevent growth; even if the spores are present, they pose no danger to the consumer.
Honey Honey is a sweet and viscous substance made by several bees, the best-known of which are honey bees. Honey is made and stored to nourish bee colonies. Bees produce honey by gathering and then refining the sugary secretions of plants (primar ...
,
corn syrup Corn syrup is a food syrup which is made from the starch of corn (called maize in many countries) and contains varying amounts of sugars: glucose, maltose and higher oligosaccharides, depending on the grade. Corn syrup is used in foods to softe ...
, and other sweeteners may contain spores, but the spores cannot grow in a highly concentrated sugar solution; however, when a sweetener is diluted in the low-oxygen, low-acid digestive system of an infant, the spores can grow and produce toxin. As soon as infants begin eating solid food, the digestive juices become too acidic for the bacterium to grow. The control of food-borne botulism caused by ''C. botulinum'' is based almost entirely on thermal destruction (heating) of the spores or inhibiting spore germination into bacteria and allowing cells to grow and produce toxins in foods. Conditions conducive of growth are dependent on various environmental factors. Growth of ''C. botulinum'' is a risk in low acid foods as defined by having a pH above 4.6 although growth is significantly retarded for pH below 4.9. In the beginning of 21st century there have been some cases and specific conditions reported to sustain growth with pH below 4.6. but at higher temperature.


Diagnosis

Physicians may consider the diagnosis of botulism based on a patient's clinical presentation, which classically includes an acute onset of bilateral cranial neuropathies and symmetric descending weakness. Other key features of botulism include an absence of fever, symmetric neurologic deficits, normal or slow heart rate and normal blood pressure, and no sensory deficits except for blurred vision. A careful history and physical examination is paramount in order to diagnose the type of botulism, as well as to rule out other conditions with similar findings, such as
Guillain–Barré syndrome Guillain–Barré syndrome (GBS) is a rapid-onset muscle weakness caused by the immune system damaging the peripheral nervous system. Typically, both sides of the body are involved, and the initial symptoms are changes in sensation or pain oft ...
,
stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
, and myasthenia gravis. Depending on the type of botulism considered, different tests for diagnosis may be indicated. * Foodborne botulism: serum analysis for toxins by bioassay in mice should be done, as the demonstration of the toxins is diagnostic. * Wound botulism: isolation of ''C. botulinum'' from the wound site should be attempted, as growth of the bacteria is diagnostic. * Adult enteric and infant botulism: isolation and growth of ''C. botulinum'' from stool samples is diagnostic. Infant botulism is a diagnosis which is often missed in the emergency room. Other tests that may be helpful in ruling out other conditions are: *
Electromyography Electromyography (EMG) is a technique for evaluating and recording the electrical activity produced by skeletal muscles. EMG is performed using an instrument called an electromyograph to produce a record called an electromyogram. An electromyog ...
(EMG) or antibody studies may help with the exclusion of myasthenia gravis and Lambert–Eaton myasthenic syndrome (LEMS). * Collection of
cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates. CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the bra ...
(CSF) protein and blood assist with the exclusion of Guillan-Barre syndrome and
stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
. * Detailed physical examination of the patient for any rash or tick presence helps with the exclusion of any tick transmitted tick paralysis.


Treatment

In the case of a diagnosis or suspicion of botulism, patients should be hospitalized immediately, even if the diagnosis and/or tests are pending. If botulism is suspected, patients should be treated immediately with antitoxin therapy in order to reduce mortality. Immediate intubation is also highly recommended, as respiratory failure is the primary cause of death from botulism. In Canada, there are currently only three antitoxin therapies available, which are accessible through Health Canada Special Access Program (SAP). The three types of antitoxin therapies are: 1) GlaxoSmithKline trivalent Types ABE, 2) NP-018 (heptavalent) Types A to G, and 3) BabyBIG, Botulism Immune Globulin Intravenous (Human) (BIG-IV) for pediatric patients under the age of one year. Outcomes vary between one and three months, but with prompt interventions, mortality from botulism ranges from less than 5 percent to 8 percent.


Vaccination

There used to be a formalin-treated
toxoid A toxoid is an inactivated toxin (usually an exotoxin) whose toxicity has been suppressed either by chemical (formalin) or heat treatment, while other properties, typically immunogenicity, are maintained. Toxins are secreted by bacteria, wherea ...
vaccine against botulism (serotypes A-E), but it was discontinued in 2011 due to declining potency in the toxoid stock. It was originally intended for people at risk of exposure. A few new vaccines are under development.


References


External links

* {{Authority control Bacteria described in 1896 Botulism
botulinum Botulinum toxin, or botulinum neurotoxin (BoNT), is a neurotoxic protein produced by the bacterium ''Clostridium botulinum'' and related species. It prevents the release of the neurotransmitter acetylcholine from axon endings at the neuromusc ...
Food microbiology Gram-positive bacteria