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arrangement of the clostridium baratii f7 toxin gene cluster with identification of a σ factor that recognizes the botulinum toxin gene cluster promoters.botulinum neurotoxin (bont) is the most poisonous substances known and its eight toxin types (a to h) are distinguished by the inability of polyclonal antibodies that neutralize one toxin type to neutralize any of the other seven toxin types. infant botulism, an intestinal toxemia orphan disease, is the most common form of human botulism in the united states. it results from swallowed spores of clostridium botulinum (or rarely, neurotoxigenic clostridium butyricum or clostridium baratii) that ge ...201424853378
update on botulinum neurotoxin use in aesthetic dermatology.botulinum toxins are among the most widely studied and versatile drugs in the medicinal market. since their extraction from clostridium botulinum, they have been harnessed and incorporated into different formulations with varied properties and actions. these products have been used to treat countless disorders such as musculoskeletal disorders, headaches, and eye disorders, among many others. in the realm of aesthetic cutaneous medicine, the evolution and creativity in the use of botulinum toxin ...201425830246
occurrence of avian botulism in korea during the period from june to september 2012.botulism is a paralytic disease caused by the botulinum neurotoxin produced by clostridium botulinum. in the summer season in korea, intensive outbreaks of avian botulism were reported in both poultry and wild birds, including five korean native chicken farms (hanhyup no.3), one pheasant (phasianus colchicus karpowi) farm, and one community of spot-billed ducks (anas poecilorhyncha). the affected domestic birds showed 24.5% to 58.3% mortality, with specific clinical signs including ataxia, limbe ...201425619016
the first case of a major avian type c botulism outbreak in poland.major outbreaks of avian type c botulism have been rarely reported from central europe. in this paper, we report the first severe outbreak of avian type c botulism in poland. in 2011-12, two epizootics caused by clostridium botulinum took place at jeziorsko dam reservoir and affected an estimated number of 5500 birds in 2011 and 1600 birds in 2012. in total, 24 species ofwaterbirds were affected, including mainly waterfowl (37.0%), shorebirds (27.0%), rallids (25.7%), and larids (9.1%). mallards ...201425518447
draft genome sequence of bivalent clostridium botulinum strain ibca10-7060, encoding botulinum neurotoxin b and a new fa mosaic type.here we report the genome sequence of a clostridium botulinum strain ibca10-7060 producing botulinum neurotoxin serotype b and a new toxin serotype. multilocus sequence typing analysis revealed that this strain belongs to a new sequence type, and whole-genome single nucleotide polymorphism analysis showed that this strain clustered with strains in lineage 2 from group i.201425502671
combined high pressure and thermal processing on inactivation of type e and nonproteolytic type b and f spores of clostridium botulinum.the aim of this study was to determine the resistance of multiple strains of the three nonproteolytic types of clostridium botulinum (seven strains of type e, eight of type b, and two of type f) spores exposed to combined high pressure and thermal processing. the resistance of spores suspended in n-(2-acetamido)-2-aminoethanesulfonic acid (aces) buffer (0.05 m, ph 7) was determined at a process temperature of 80°c with high pressures of 600, 650, and 700 mpa using a laboratory-scale pressure tes ...201425474050
role of neurotoxin associated proteins in the low ph induced structural changes in the botulinum neurotoxin complex.botulinum neurotoxin (bont) produced by the bacterium clostridium botulinum as a complex with naps causes botulism. it has been known that the naps protect the toxin from both extremes of phs and proteases of the gi tract. in an attempt to emulate the physiological conditions encountered by the toxin, we examined bont/a, bont/a complex, and naps under different ph conditions and monitored their structural characteristics by far-uv cd and thermal denaturation analysis. bont/a complex showed the m ...201425408485
draft genome sequences of two clostridium botulinum group ii (nonproteolytic) type b strains (db-2 and kapb-3).clostridium botulinum is important for food safety and studies of neurotoxins associated with human botulism. we present the draft genome sequences of two strains belonging to group ii type b: one collected from pacific ocean sediments (db-2) and another obtained during a botulism outbreak (kapb-3).201425377702
functional dissection of the clostridium botulinum type b hemagglutinin complex: identification of the carbohydrate and e-cadherin binding sites.botulinum neurotoxin (bont) inhibits neurotransmitter release in motor nerve endings, causing botulism, a condition often resulting from ingestion of the toxin or toxin-producing bacteria. bonts are always produced as large protein complexes by associating with a non-toxic protein, non-toxic non-hemagglutinin (ntnh), and some toxin complexes contain another non-toxic protein, hemagglutinin (ha), in addition to ntnh. these accessory proteins are known to increase the oral toxicity of the toxin dr ...201425340348
botulinum toxin type a products are not interchangeable: a review of the evidence.botulinum toxin type a (bonta) products are injectable biologic medications derived from clostridium botulinum bacteria. several different bonta products are marketed in various countries, and they are not interchangeable. differences between products include manufacturing processes, formulations, and the assay methods used to determine units of biological activity. these differences result in a specific set of interactions between each bonta product and the tissue injected. consequently, the pr ...201425336912
8-hydroxyquinoline and hydroxamic acid inhibitors of botulinum neurotoxin bont/a.we describe here the state of the art of certain aspects concerning potential small molecule therapy directed toward botulism, by inhibition of the zinc-protease containing light chain (lc) of botulinum neurotoxin bont/a from the anaerobic bacillus clostridium botulinum. botulinum neurotoxins (bonts) are comprised of eight serologically-distinct proteins (a - h), several of which are further divided, such as bont/a which has five subtypes. the bonts are the most toxic substances known to mankind ...201425335884
"inconvenient truths" in the pursuit of scientific knowledge and public health. 201424106297
a novel strain of clostridium botulinum that produces type b and type h botulinum toxins.clostridium botulinum strain ibca10-7060, isolated from a patient with infant botulism, produced botulinum neurotoxin type b (bont/b) and another bont that, by use of the standard mouse bioassay, could not be neutralized by any of the centers for disease control and prevention-provided monovalent polyclonal botulinum antitoxins raised against bont types a-g.201424106296
molecular characterization of a novel botulinum neurotoxin type h gene.we sequenced the 2 botulinum toxin gene clusters of clostridium botulinum strain ibca10-7060 type bh. the sequence of bont/h differed substantially from the sequences of the 7 known bont genes for toxin types a-g. the 5' one-third terminus of bont/h that codes for the botulinum toxin light chain differed markedly from the light chain coding sequences of toxin types a-g. the 3' two-thirds terminus of bont/h that codes for the botulinum toxin heavy chain contained a novel hn translocation domain c ...201424106295
botulinum neurotoxins: more and more diverse and fascinating toxic proteins. 201424106294
novel clostridium botulinum toxin and dual use research of concern issues. 201424106293
prevention of rhoa activation and cofilin-mediated actin polymerization mediates the antihypertrophic effect of adenosine receptor agonists in angiotensin ii- and endothelin-1-treated cardiomyocytes.adenosine receptor activation has been shown to be associated with diminution of cardiac hypertrophy and it has been suggested that endogenously produced adenosine may serve to blunt pro-hypertrophic processes. in the present study, we determined the effects of two pro-hypertrophic stimuli, angiotensin ii (ang ii, 100 nm) and endothelin-1 (et-1, 10 nm) on ras homolog gene family, member a (rhoa)/rho-associated, coiled-coil containing protein kinase (rock) activation in cultured neonatal rat vent ...201424096734
the clo3403/clo3404 two-component system of clostridium botulinum e1 beluga is important for cold shock response and growth at low temperatures.in order to survive a temperature downshift, bacteria have to sense the changing environment and adjust their metabolism and structure. two-component signal transduction systems (tcss) play a central role in sensing and responding to many different environmental stimuli. although the nonproteolytic (group ii) clostridium botulinum represents a major hazard in chilled foods, the cold adaption mechanisms of group ii c. botulinum organisms are not known. here, we show that the clo3403/clo3404 tcs o ...201424185852
vaccination of cattle with a recombinant bivalent toxoid against botulism serotypes c and d.cattle botulism is a fatal intoxication caused by botulinum neurotoxins (bonts) produced by clostridium botulinum serotypes c and d resulting in economic losses. vaccination is the most effective way to control botulism. however, the commercially available vaccines are difficult and hazardous to produce. neutralizing antibodies against the c-terminal fragment of the bont heavy chain (hc) are known to protect against lethal doses of bonts. we report the vaccination of cattle with a previously tes ...201424252701
quantitative real-time pcr for detection of neurotoxin genes of clostridium botulinum types a, b and c in equine samples.botulism in horses in the usa is attributed to clostridium botulinum types a, b or c. in this study, a duplex quantitative real-time pcr (qpcr) for detection of the neurotoxin genes of c. botulinum types a and b, and a singleplex qpcr for detection of the neurotoxin gene of c. botulinum type c, were optimized and validated for equine gastrointestinal, faecal and feed samples. the performance of these assays was evaluated and compared to the standard mouse bioassay (mba) using 148 well-characteri ...201424252222
analysis of the genetic distribution among members of clostridium botulinum group i using a novel multilocus sequence typing (mlst) assay.clostridium botulinum is the etiological agent of botulism. due to food-borne poisoning and the potential use of the extremely toxic botulinum neurotoxin (bont) from c. botulinum in bioterror or biocrime related actions, reliable high resolution typing methods for discriminating c. botulinum strains are needed. partial sequencing of the adk, atph, gyrb, proc, rpod and spo0a genes from 51 various c. botulinum/sporogenes isolates was performed, resulting in 37 different sequence types (sts). analy ...201424246230
a quantitative bifunctional in vitro potency assay for botulinum neurotoxin serotype a.botulinum neurotoxin type a (bonta) is one of seven serotypes produced by clostridium botulinum (types a thru g) and is the serotype most widely used to treat both cosmetic and medical conditions. potency for botulinum toxin preparations is expressed in mouse ld50 units. there is a need to develop a non-animal based replacement for this potency assay.201424333955
comparison of assembled clostridium botulinum a1 genomes revealed their evolutionary relationship.clostridium botulinum encompasses bacteria that produce at least one of the seven serotypes of botulinum neurotoxin (bont/a-g). the availability of genome sequences of four closely related type a1 or a1(b) strains, as well as the a1-specific microarray, allowed the analysis of their genomic organizations and evolutionary relationship. the four genomes share >90% core genes and >96% functional groups. phylogenetic analysis based on cog shows closer relations of the a1(b) strain, nctc 2916, to b1 ...201424369123
positive regulation of botulinum neurotoxin gene expression by cody in clostridium botulinum atcc 3502.botulinum neurotoxin, produced mainly by the spore-forming bacterium clostridium botulinum, is the most poisonous biological substance known. here, we show that cody, a global regulator conserved in low-g+c gram-positive bacteria, positively regulates the botulinum neurotoxin gene expression. inactivation of cody resulted in decreased expression of bota, encoding the neurotoxin, as well as in reduced neurotoxin synthesis. complementation of the cody mutation in trans rescued neurotoxin synthesis ...201425281376
invasive slug populations (arion vulgaris) as potential vectors for clostridium botulinum.norwegian meadows, including those for silage production, are recently found heavily invaded by the slug arion vulgaris in exposed areas. as a consequence, large numbers of slugs might contaminate grass silage and cause a possible threat to animal feed quality and safety. it is well known that silage contaminated by mammalian or avian carcasses can lead to severe outbreaks of botulism among livestock. invertebrates, especially fly-larvae (diptera), are considered important in the transfer of clo ...201425277214
plasmidome interchange between clostridium botulinum, clostridium novyi and clostridium haemolyticum converts strains of independent lineages into distinctly different pathogens.clostridium botulinum (group iii), clostridium novyi and clostridium haemolyticum are well-known pathogens causing animal botulism, gas gangrene/black disease, and bacillary hemoglobinuria, respectively. a close genetic relationship exists between the species, which has resulted in the collective term c. novyi sensu lato. the pathogenic traits in these species, e.g., the botulinum neurotoxin and the novyi alpha toxin, are mainly linked to a large plasmidome consisting of plasmids and circular pr ...201425254374
botulinum neurotoxin subtype a4 originating from nontoxigenic clostridium botulinum. 201425239910
holotoxin activity of botulinum neurotoxin subtype a4 originating from a nontoxigenic clostridium botulinum expression system.clostridium botulinum subtype a4 neurotoxin (bont/a4) is naturally expressed in the dual-toxin-producing c. botulinum strain 657ba at 100× lower titers than bont/b. in this study, we describe purification of recombinant bont/a4 (rbont/a4) expressed in a nonsporulating and nontoxigenic c. botulinum expression host strain. the rbont/a4 copurified with nontoxic toxin complex components provided in trans by the expression host and was proteolytically cleaved to the active dichain form. activity of t ...201425239905
infant botulism and indications for administration of botulism immune globulin.infant botulism is caused by the ingestion of clostridium botulinum spores and leads to a life-threatening descending motor weakness and flaccid paralysis in infant children. this disease presents with symptoms such as constipation, weakness, and hypotonia and can lead to respiratory failure. botulism immune globulin (big) was created to treat this deadly disease and functions by neutralizing all systemically circulating botulism toxins. it is indicated in children with clinically diagnosed infa ...201424488164
molecular characterization of clostridium botulinum isolates from foodborne outbreaks in thailand, 2010.thailand has had several foodborne outbreaks of botulism, one of the biggest being in 2006 when laboratory investigations identified the etiologic agent as clostridium botulinum type a. identification of the etiologic agent from outbreak samples is laborious using conventional microbiological methods and the neurotoxin mouse bioassay. advances in molecular techniques have added enormous information regarding the etiology of outbreaks and characterization of isolates. we applied these methods in ...201424475015
identification of the interaction region between hemagglutinin components of the botulinum toxin complex.the large toxin complex (l-tc) produced by clostridium botulinum is formed from the m-tc (bont/ntnha complex) by conjugation of m-tc with ha-33/ha-17 trimer consists of two ha-33 proteins and a single ha-17 protein. this association is mediated by ha-70, which interacts with ha-17. the current study aims to identify the regions of the ha-70 molecule that adhere to the ha-33/ha-17 complex. products from limited proteolysis of ha-70 were resolved by sds-page and transferred onto pvdf membranes, wh ...201424472509
infant botulism in andalusia (southern spain).infant botulism (ib) is caused by the intestinal colonization by clostridium botulinum in the first year of life and its subsequent production of neurotoxins. traditionally, ib has been associated to honey consumption. ib cases tend to cluster in geographic regions. in europe, ib is a rare disorder. from 1976 through 2006, 65 cases were identified in 13 european countries. in spain, in the last 15 years, most of the cases have been reported in one region, andalusia (southern spain). a specific t ...201424468429
whole-genome single-nucleotide-polymorphism analysis for discrimination of clostridium botulinum group i strains.clostridium botulinum is a genetically diverse gram-positive bacterium producing extremely potent neurotoxins (botulinum neurotoxins a through g [bont/a-g]). the complete genome sequences of three strains harboring only the bont/a1 nucleotide sequence are publicly available. although these strains contain a toxin cluster (ha(+) orfx(-)) associated with hemagglutinin genes, little is known about the genomes of subtype a1 strains (termed ha(-) orfx(+)) that lack hemagglutinin genes in the toxin ge ...201424463972
a case of infant botulism infection due to consumption of untreated well-water.a 7-week-old boy with flaccid paralysis was diagnosed with infant botulism caused by clostridium botulinum toxin type a. in this case of infant botulism, untreated well-water was identified as a potential source of this infection.201424461790
draft genome sequence of clostridium botulinum type b strain osaka05, isolated from an infant patient with botulism in japan.clostridium botulinum strain osaka05, which has been isolated from an infant patient with botulism in japan, is the first strain producing botulinum neurotoxin subtype b6. here, we report the draft genome sequence of c. botulinum osaka05.201424459252
meta-analysis of d-values of proteolytic clostridium botulinum and its surrogate strain clostridium sporogenes pa 3679.foodborne botulism is a serious disease resulting from ingestion of preformed clostridium botulinum neurotoxin in foodstuff. since the 19th century, the heat resistance of this spore forming bacteria has been extensively studied in order to guarantee the public health associated with low acidic, ambient stable products. the most largely used heat resistance parameters in thermal settings of such products are the d121.1°c values (time required to have a 10-fold decrease of the spore count, at 121 ...201424448274
infant botulism in costa rica: first report from central america.clostridium botulinum is known to cause descending paralysis in infants throughout the world.201424423723
purification, crystallization and preliminary x-ray analysis of an ha17-ha70 (ha2-ha3) complex from clostridium botulinum type c progenitor toxin.the haemagglutinin (ha) complex of clostridium botulinum type c toxin is composed of three types of subcomponents: ha33, ha17 and ha70 (also known as ha1, ha2 and ha3, respectively). here, a 260 kda ha17-ha70 complex was crystallized. his-tagged ha17 and maltose-binding-protein-tagged ha70 were expressed in escherichia coli and their complex was affinity-purified using a combination of amylose resin chromatography and nickel-nitrilotriacetic acid agarose chromatography. diffraction data were col ...201424419620
the same clade of clostridium botulinum strains is causing avian botulism in southern and northern europe.avian botulism is a paralytic disease caused by clostridium botulinum-produced botulinum neurotoxins (bonts), most commonly of type c/d. it is a serious disease of waterbirds and poultry flocks in many countries in europe. the objective of this study was to compare the genetic relatedness of avian c. botulinum strains isolated in spain with strains isolated in sweden using pulsed-field gel electrophoresis (pfge). fifteen strains were isolated from spanish waterbirds using an immunomagnetic separ ...201424418766
two novel toxin variants revealed by whole-genome sequencing of 175 clostridium botulinum type e strains.we sequenced 175 clostridium botulinum type e strains isolated from food, clinical, and environmental sources from northern canada and analyzed their botulinum neurotoxin (bont) coding sequences (cdss). in addition to bont/e1 and bont/e3 variant types, neurotoxin sequence analysis identified two novel bont type e variants termed e10 and e11. strains producing type e10 were found along the eastern coastlines of hudson bay and the shores of ungava bay, while strains producing type e11 were only fo ...201425107978
effect of sporulation medium and its divalent cation content on the heat and high pressure resistance of clostridium botulinum type e spores.clostridium (c.) botulinum type e belongs to the non-proteolytic physiological c. botulinum group ii and produces the highly potent botulinum neurotoxin e (bont/e) even at refrigerated temperatures. as c. botulinum type e spores are highly prevalent in aquatic environments, seafood and fishery products are commonly associated with this organism. hydrostatic high pressure (hhp) treatments, or treatments combining hhp with elevated temperatures (hhpt), can be used to improve traditional preservati ...201425084658
identification and genetic characterization of clostridium botulinum serotype a strains from commercially pasteurized carrot juice.clostridium botulinum is an important foodborne pathogen capable of forming heat resistant endospores and producing deadly botulinum neurotoxins (bonts). in 2006, c. botulinum was responsible for an international outbreak of botulism attributed to the consumption of commercially pasteurized carrot juice. the purpose of this study was to isolate and characterize strains of c. botulinum from the adulterated product. carrot juice bottles retrieved from the manufacturing facility were analyzed for t ...201425084657
three classes of plasmid (47-63 kb) carry the type b neurotoxin gene cluster of group ii clostridium botulinum.pulsed-field gel electrophoresis and dna sequence analysis of 26 strains of group ii (nonproteolytic) clostridium botulinum type b4 showed that 23 strains carried their neurotoxin gene cluster on a 47-63 kb plasmid (three strains lacked any hybridization signal for the neurotoxin gene, presumably having lost their plasmid). unexpectedly, no neurotoxin genes were found on the chromosome. this apparent constraint on neurotoxin gene transfer to the chromosome stands in marked contrast to group i c. ...201425079343
new insight in the epidemiology of avian botulism outbreaks: necrophagous flies as vectors of clostridium botulinum type c/d.avian botulism outbreaks spread through the bird carcass-maggot cycle, in which clostridium botulinum and blowflies interact to ensure their reproduction in a mutualistic relationship where neurotoxin/spore-bearing maggot is one of the keystones. here we investigated the hypothesis that adult blowflies may also play a significant role in botulism outbreaks by carrying c. botulinum cells between carcasses. we carried out a field experiment placing bird carcasses free of c. botulinum type c/d in c ...201425079304
botulinum toxin for myofascial pain syndromes in adults.this is an updated version of the original cochrane review published in issue 4, 2012. myofascial pain syndrome (mps) is a regional muscular pain syndrome characterised by the presence of trigger points, which are painful points in one or more muscles. the pain can be felt at the site where the trigger point is located or it can be felt away from that place when the muscle is pressed (referred pain). botulinum toxin is a protein produced by the bacterium clostridium botulinum and is a potent neu ...201425062018
onabotulinumtoxina (botox(®)): a review of its use in the treatment of urinary incontinence in patients with multiple sclerosis or subcervical spinal cord injury.onabotulinumtoxina (botox(®)) is a type a neurotoxin derived from clostridium botulinum bacteria that is approved as treatment for urinary incontinence (ui) in patients with neurogenic detrusor overactivity resulting from multiple sclerosis (ms) or subcervical spinal cord injury (sci) who are not adequately treated by antimuscarinics. this article reviews the pharmacology of intradetrusor onabotulinumtoxina in this indication. the presumed mode of action of onabotulinumtoxina in bladder disorder ...201425060982
a 59-year-old man with acute onset of paralysis.botulism is a neuroparalytic illness resulting from the action of a potent toxin produced by the organism clostridium botulinum. it can present with a classic triad of clear mentation, bulbar palsy and symmetric descending paralysis. treatment is symptomatic and includes a botulinum antitoxin.201425054790
host-cell specificity and transcytosis of nontoxic nonhemagglutinin protein of botulinum neurotoxin serotype d.serotype d botulinum toxin (bont) complex (tc), a causative agent of foodborne botulism in animals, traverses the gastrointestinal tract and circulation, eventually becoming localized in neuromuscular junctions, where the serotype d bont cleaves snare substrate synaptobrevin ii involved in neurotransmitter release. during this process, bont must pass through cells, thus from the intestinal lumen to the cells of the intestinal tract and blood vessels. the botulinum tc is formed by association of ...201425041523
distinguishing highly-related outbreak-associated clostridium botulinum type a(b) strains.in the united states, most clostridium botulinum type a strains isolated during laboratory investigations of human botulism demonstrate the presence of an expressed type a botulinum neurotoxin (bont/a) gene and an unexpressed bont/b gene. these strains are designated type a(b). the most common pulsed-field gel electrophoresis (pfge) pattern in the c. botulinum pulsenet database is composed of a(b) strains. the purpose of this study was to evaluate the ability of genome sequencing and multi-loci ...201425031122
chronic botulism in a saxony dairy farm: sources, predisposing factors, development of the disease and treatment possibilities.the aim of this study is to investigate clostridium botulinum at a saxony dairy farm with 159 cows and 18 heifers. the animals exhibited clinical symptoms of chronic botulism. to determine the source of the infection, feces, blood, organs, and gastrointestinal fluids of dead or euthanized cows; as well as soil, water, silage and manure were tested for c. botulinum spores and bonts using elisa. bont/c and c. botulinum type c were detected in 53% and 3% of tested animals, respectively, while bont/ ...201424997242
hidradenitis suppurativa treated with clostridium botulinum toxin a. 201424986398
botulism outbreaks in natural environments - an update.clostridium botulinum comprises a diverse group of botulinum toxin-producing anaerobic rod-shaped spore-forming bacteria that are ubiquitously distributed in soils and aquatic sediments. decomposition of plants, algae, and animals creates anaerobic environments that facilitate growth of c. botulinum, which may then enter into food webs leading to intoxication of animals. via saprophytic utilization of nutrients, the bacteria rapidly sporulate, creating a reservoir of highly robust spores. in the ...201424966853
botulism as a food poisoning: what is it?botulism is a rare but potentially life-threatening neuroparalytic syndrome resulting from the action of a neurotoxin elaborated by the microorganism clostridium botulinum. this disease has a lengthy history; the first investigation of botulism occurred in the 1820s with a case report on hundreds of patients with "sausage poisoning" in a southern german town. several decades later in belgium, the association was demonstrated between a neuromuscular paralysis and ham infected by a spore forming b ...201424961027
production of recombinant botulism antigens: a review of expression systems.botulism is a paralytic disease caused by intoxication with neurotoxins produced by clostridium botulinum. despite their similar mechanism of action, the botulinum neurotoxins (bont) are classified in eight serotypes (a to h). as to veterinary medicine, the impact of this disease is essentially economic, since different species of production animals can be affected, especially by bont/c and d. in human health, botulism is feared in a possible biological warfare, what would involve mainly the bon ...201424930432
alternative sigma factors sigf, sige, and sigg are essential for sporulation in clostridium botulinum atcc 3502.clostridium botulinum produces heat-resistant endospores that may germinate and outgrow into neurotoxic cultures in foods. sporulation is regulated by the transcription factor spo0a and the alternative sigma factors sigf, sige, sigg, and sigk in most spore formers studied to date. we constructed mutants of sigf, sige, and sigg in c. botulinum atcc 3502 and used quantitative reverse transcriptase pcr and electron microscopy to assess their expression of the sporulation pathway on transcriptional ...201424928875
emerging treatments for overactive bladder: clinical potential of botulinum toxins.overactive bladder (oab) is a symptom syndrome including urgency, frequency, and nocturia - with or without incontinence. it is a common manifestation of detrusor overactivity (do). do is a urodynamic observation of spontaneous or provoked contractions of the detrusor muscle is seen during the filling phase of the micturition cycle. oab is, therefore, both a motor and sensory disorder. botulinum toxin is a purified form of the neurotoxin from clostridium botulinum and has been used in medicine f ...201424892033
botulinum toxin a: a new option for treatment of chronic migraine with medication overuse.the application of botulinum toxin for several pathological conditions has been largely debated in the last decades and its use has been definitively consolidated for disorders related to increased muscle tone and hyperidrosis. botulinum neurotoxin (bont-a) is a potent toxin produced by an anaerobic bacterium, clostridium botulinum, which presents several pharmacological proprieties, but also different and serious contraindications. as chronic migraine (cm) is commonly reported as a serious and ...201424867833
prioritizing drug targets in clostridium botulinum with a computational systems biology approach.a computational and in silico system level framework was developed to identify and prioritize the antibacterial drug targets in clostridium botulinum (clb), the causative agent of flaccid paralysis in humans that can be fatal in 5 to 10% of cases. this disease is difficult to control due to the emergence of drug-resistant pathogenic strains and the only available treatment antitoxin which can target the neurotoxin at the extracellular level and cannot reverse the paralysis. this study framework ...201424837790
clarification regarding novel clostridium botulinum toxin. 201424808390
clostridium botulinum toxin statement from the director of the california department of public health. 201424808389
eutrophication and bacterial pathogens as risk factors for avian botulism outbreaks in wetlands receiving effluents from urban wastewater treatment plants.due to the scarcity of water resources in the "mancha húmeda" biosphere reserve, the use of treated wastewater has been proposed as a solution for the conservation of natural threatened floodplain wetlands. in addition, wastewater treatment plants of many villages pour their effluent into nearby natural lakes. we hypothesized that certain avian pathogens present in wastewater may cause avian mortalities which would trigger avian botulism outbreaks. with the aim of testing our hypothesis, 24 loca ...201424795377
[infant botulism].infant botulism is a paralytic syndrome which manifests as a result of ingesting spores of the toxin secreting bacterium clostridium botulinum by infants. as opposed to botulism in adults, treating infant botulism with horse antiserum was not approved due to several safety issues. this restriction has led to the development of human botulism immune globulin intravenous (big-iv; sells under babybig). in this article we review infant botulism and the advantages of treating it with big-iv.201424791561
[infant botulism after honey exposure].infant botulism is a rare neuroparalytic disease caused by the neurotoxin of clostridium botulinum. initial clinical features are constipation, poor feeding, descending hypotonia, drooling, irritability, weak crying and cranial nerve dysfunctions. we describe the clinical progression and the epidemiological investigation carried out in a 3-month-old infant. better knowledge of the disease should allow faster diagnosis and adequate management. we emphasize the risks associated with honey exposure ...201424768073
random mutagenesis of bont/e hc nanobody to construct a secondary phage-display library.to construct secondary mutant phage-display library of recombinant single variable domain (vhh) against botulinum neurotoxin e by error-prone pcr.201424766494
relationship between gastrointestinal dysbiosis and clostridium botulinum in dairy cows.the gastrointestinal tract is a balanced ecosystem that can get out of balance and predisposed to clostridial diseases or other pathological conditions. the objective of the present study was to evaluate the gut microbiota in dairy cows suffering from chronic botulism. cows were investigated for clostridium (c.) botulinum in faeces and rumen fluids. in order to study the relationship between botulism and gastrointestinal microbiota, faeces and rumen fluid were tested for bacterial composition us ...201424747040
methods and difficulties in detection of clostridium botulinum and its toxins.the aim of this work was to present selected data regarding traditional and modern methods for c. botulinum and its toxins detection. in this article, methods based on culturing techniques, mouse bioassay, immunological techniques, chromatography and pcr, pfge, rflp, aflp are described. the mentioned techniques were evaluated considering their usefulness in the samples examination, genotyping of strains and the diagnostics of botulism.201424724492
food-borne botulism in japan in march 2012.in march 2012, two patients were transported urgently to the hospital in tottori prefecture, japan, because of symptoms suggestive of botulism. botulinum neurotoxin type a was detected in the clinical specimens and the food consumed by the two patients (vacuum packed adzuki-batto, a sweet adzuki bean soup containing noodles). we were able to make a prompt diagnosis of food botulism associated with the consumption of adzuki-batto, from which the causative pathogen clostridium botulinum ab was cul ...201424709046
botulinum toxin: the midas touch.botulinum toxin (bt) is a natural molecule produced during growth and autolysis of bacterium called clostridium botulinum. use of bt for cosmetic purposes has gained popularity over past two decades, and recently, other therapeutic uses of bt has been extensively studied. bt is considered as a minimally invasive agent that can be used in the treatment of various orofacial disorders and improving the quality of life in such patients. the objective of this article is to review the nature, mechanis ...201424678189
view from the front lines: an emergency medicine perspective on clostridial infections in injection drug users.injection drug use (idu), specifically non-intravenous "skin-popping" of heroin, seems to provide optimal conditions for clostridial infection and toxin production. idu is therefore a major risk factor for wound botulism and clostridial necrotizing soft tissue infections (nsti) and continues to be linked to cases of tetanus. case clusters of all 3 diseases have occurred among idus in western u.s. and europe. medical personnel who care for the idu population must be thoroughly familiar with the c ...201425230330
functional characterisation of germinant receptors in clostridium botulinum and clostridium sporogenes presents novel insights into spore germination systems.clostridium botulinum is a dangerous pathogen that forms the highly potent botulinum toxin, which when ingested causes a deadly neuroparalytic disease. the closely related clostridium sporogenes is occasionally pathogenic, frequently associated with food spoilage and regarded as the non-toxigenic equivalent of group i c. botulinum. both species form highly resistant spores that are ubiquitous in the environment and which, under favourable growth conditions germinate to produce vegetative cells. ...201425210747
genetic characterization and comparison of clostridium botulinum isolates from botulism cases in japan between 2006 and 2011.genetic characterization was performed for 10 group i clostridium botulinum strains isolated from botulism cases in japan between 2006 and 2011. of these, 1 was type a, 2 were type b, and 7 were type a(b) {carrying a silent bont/b [bont/(b)] gene} serotype strains, based on botulinum neurotoxin (bont) production. the type a strain harbored the subtype a1 bont gene (bont/a1), which is associated with the ha gene cluster. the type b strains carried bont/b5 or bont/b6 subtype genes. the type a(b) s ...201425192986
outbreak of type e foodborne botulism linked to traditionally prepared salted fish in ontario, canada.on april 17, 2012, two adult females presented to the hospital with symptoms of botulism. patient a displayed shortness of breath, increasing lethargy, ptosis, and fixed and dilated pupils, and was intubated after admission. patient b presented with shortness of breath, vomiting, and stridor. both patients consumed a meal consisting of a traditionally prepared salted fish, fesikh, on the evening of april 16 during a gathering to celebrate sham el-nessim, an egyptian holiday marking the beginning ...201425188279
investigation of clostridium botulinum in commercial poultry farms in france between 2011 and 2013.between 2011 and 2013, 17 poultry botulism outbreaks were investigated in france. all cases were associated with clostridium botulinum type c-d. presence of c. botulinum was studied in seven areas: poultry house, changing room, ventilation system, surroundings, animal reservoirs, water, and feed. swabs, litter, soil, darkling beetles, rodents and wild bird droppings, feed and water samples were collected. the presence of c. botulinum type c-d in the environment of affected flocks was detected in ...201425175400
egypt's red sea coast: phylogenetic analysis of cultured microbial consortia in industrialized sites.the red sea possesses a unique geography, and its shores are rich in mangrove, macro-algal and coral reef ecosystems. various sources of pollution affect red sea biota, including microbial life. we assessed the effects of industrialization on microbes along the egyptian red sea coast at eight coastal sites and two lakes. the bacterial communities of sediment samples were analyzed using bacterial 16s rdna pyrosequencing of v6-v4 hypervariable regions. the taxonomic assignment of 131,402 significa ...201425157243
complete nucleotide sequence of a plasmid containing the botulinum neurotoxin gene in clostridium botulinum type b strain 111 isolated from an infant patient in japan.botulinum neurotoxins (bonts) are highly potent toxins that are produced by clostridium botulinum. we determined the complete nucleotide sequence of a plasmid containing the botulinum neurotoxin gene in c. botulinum type b strain 111 in order to obtain an insight into the toxigenicity and evolution of the bont gene in c. botulinum. group i c. botulinum type b strain 111 was isolated from the first case of infant botulism in japan in 1995. in previous studies, botulinum neurotoxin subtype b2 (bon ...201425149145
clostridium botulinum strains producing bont/f4 or bont/f5.botulinum neurotoxin type f (bont/f) may be produced by clostridium botulinum alone or in combination with another toxin type such as bont/a or bont/b. type f neurotoxin gene sequences have been further classified into seven toxin subtypes. recently, the genome sequence of one strain of c. botulinum (af84) was shown to contain three neurotoxin genes (bont/f4, bont/f5, and bont/a2). in this study, eight strains containing bont/f4 and seven strains containing bont/f5 were examined. culture superna ...201424632257
high-resolution crystal structure of ha33 of botulinum neurotoxin type b progenitor toxin complex.botulinum neurotoxins (bonts) are produced as progenitor toxin complexes (ptcs) by clostridium botulinum. the ptcs are composed of bont and non-toxic neurotoxin-associated proteins (naps), which serve to protect and deliver bont through the gastrointestinal tract in food borne botulism. ha33 is a key nap component that specifically recognizes host carbohydrates and helps enrich ptc on the intestinal lumen preceding its transport across the epithelial barriers. here, we report the crystal structu ...201424631690
detection of c. botulinum types in honey by mpcr.the aim of this study was to determine the prevalence of clostridium botulinum in honey samples using conventional methods and multiplex pcr (mpcr). a total number of 150 honey samples were randomly collected from apiaries, retail shops, weekly open bazaars, and supermarkets in samsun, turkey. of 150 honey samples, 4 (2.6%) were positive for the botulinum neurotoxin gene by mpcr analysis. a total of 4 c. botulinum isolates were obtained from the mpcr positive samples, of which 3 were type a and ...201424621137
mechano- and metabosensitive alterations after injection of botulinum toxin into gastrocnemius muscle.this study was designed to investigate effects of motor denervation by clostridium botulinum toxin serotype a (bont/a) on the afferent activity of fibers originating from the gastrocnemius muscle of rats. animals were randomized in two groups, 1) untreated animals acting as control and 2) treated animals in which the toxin was injected in the left muscle. locomotor activity was evaluated once per day during 12 days with a test based on footprint measurements of walking rats (sciatic functional i ...201424615939
three enzymatically active neurotoxins of clostridium botulinum strain af84: bont/a2, /f4, and /f5.botulinum neurotoxins (bonts) are produced by various species of clostridia and are potent neurotoxins which cause the disease botulism, by cleaving proteins needed for successful nerve transmission. there are currently seven confirmed serotypes of bonts, labeled a-g, and toxin-producing clostridia typically only produce one serotype of bont. there are a few strains (bivalent strains) which are known to produce more than one serotype of bont, producing either both bont/a and /b, bont/a and /f, o ...201424605815
rare presentation of botulism with generalized fasciculations.botulism is a dreadful, life-threatening, neuroparalytic disease caused by gram positive bacteria clostridium botulinum. food borne botulism has been described following ingestion of preformed toxins in canned food or food products that have not been preserved properly. botulinum toxin acts on neuromuscular junction and manifests as ophthalmoplegia, bulbar and limb weakness, and autonomic features along with respiratory compromise. the literature and case reports regarding neuroparalytic botulis ...201424600582
crystallization and preliminary x-ray analysis of a novel haemagglutinin component of the toxin complex of serotype c clostridium botulinum.the botulinum toxin complex, the causative agent of botulism, passes through the intestinal wall via sugar-chain-dependent cell binding of a haemagglutinin of 33 kda molecular weight (ha-33). the amino-acid sequence of the c-terminal half of ha-33 of the serotype c strain yoichi (c-yoichi) shares only 46% identity with those of the major serotype c strains. additionally, c-yoichi ha-33 exhibits a unique sugar-binding specificity. in the present work, c-yoichi ha-33 was expressed in escherichia c ...201424598930
transcriptomic analysis of (group i) clostridium botulinum atcc 3502 cold shock response.profound understanding of the mechanisms foodborne pathogenic bacteria utilize in adaptation to the environmental stress they encounter during food processing and storage is of paramount importance in design of control measures. chill temperature is a central control measure applied in minimally processed foods; however, data on the mechanisms the foodborne pathogen clostridium botulinum activates upon cold stress are scarce. transcriptomic analysis on the c. botulinum atcc 3502 strain upon temp ...201424587151
binding of clostridium botulinum c3 exoenzyme to intact cells.c3 from clostridium botulinum (c3) specifically modifies rho gtpases rhoa, rhob, and rhoc by mono-adp-ribosylation. the confined substrate profile of c3 is the basis for its use as pharmacological tool in cell biology to study cellular functions of rho gtpases. although c3 exoenzyme does not possess a cell-binding/-translocation domain, c3 is taken up by intact cells via an unknown mechanism. in the present work, binding of c3 to the hippocampus-derived ht22 cells and j774a.1 macrophages was cha ...201424584821
[traumatic wound botulism].botulism is a rare illness caused by a potent neurotoxin produced by the bacterium of the clostridium family. clostridium botulinum is the most frequent one, but clostridium baratti and clostridium butyricum are also neurotoxins producers. there are seven neurotoxins types, a to g; a, b, e, f and g cause human botulism. every neurotoxin type blocks cholinergic transmission at the myoneural junction. the least frequent syndrome results from clostridium botulinum colonization of a wound and it is ...201424584800
intracellular trafficking of clostridium botulinum c2 toxin.clostridium botulinum c2 toxin is a binary toxin composed of an enzymatic component (c2i) and binding component (c2ii). the activated binding component (c2iia) forms heptamers and the oligomer with c2i is taken up by receptor-mediated endocytosis. we investigated the intracellular trafficking of c2 toxin. when mdck cells were incubated with c2i and c2iia at 37 °c, c2i colocalized with c2iia in cytoplasmic vesicles at 5 min, and c2i then disappeared (15 min incubation and later), and c2iia was ob ...201424582943
equine grass sickness.equine grass sickness (egs; equine dysautonomia) is a polyneuronopathy affecting both the central and the peripheral nervous systems of horses. as the name implies, egs almost exclusively affects grazing horses, resulting in the development of a characteristic array of clinical signs, most of which can be attributed to neuronal degeneration in the autonomic and enteric nervous systems. varying disease severities occur, largely determined by the extent of neuronal degeneration in the myenteric an ...201424580639
type a botulinum neurotoxin complex proteins differentially modulate host response of neuronal cells.type a botulinum neurotoxin (bont/a), the most potent poison known to mankind, is produced by clostridium botulinum type a as a complex with neurotoxin-associated proteins (naps). currently bont/a in purified and complex forms are both available in therapeutic and cosmetic applications to treat neuromuscular disorders. whereas xeomin(®) (incobotulinumtoxin a, merz pharmaceuticals, germany) is free from complexing proteins, botox(®) (onabotulinumtoxin a, allergan, usa) contains naps, which by the ...201424560879
medical treatment for botulism.botulism is an acute paralytic illness caused by a neurotoxin produced by clostridium botulinum. supportive care, including intensive care, is key but the role of other medical treatments is unclear. this is an update of a review first published in 2011.201424558013
high sensitivity detection of active botulinum neurotoxin by glyco-quantitative polymerase chain-reaction.the sensitive detection of highly toxic botulinum neurotoxin (bont) from clostridium botulinum is of critical importance because it causes human illnesses if foodborne or introduced in wounds and as an iatrogenic substance. moreover, it has been recently considered a possible biological warfare agent. over the past decade, significant progress has been made in bont detection technologies, including mouse lethality assays, enzyme-linked immunosorbent assays, and endopeptidase assays and by mass s ...201424506443
infant botulism with prolonged faecal excretion of botulinum neurotoxin and clostridium botulinum for 7 months.in finland in april 2010, a 3-month old baby was diagnosed with type a infant botulism. he excreted botulinum neurotoxin and/or clostridium botulinum in his faeces until november 2010. five months of excretion was after clinical recovery and discharge from hospital. c. botulinum isolates recovered from the household dust in the patient's home were genetically identical to those found in the infant's stool samples. long-term faecal excretion of c. botulinum may pose a possible health risk for the ...201423688392
an atypical clostridium strain related to the clostridium botulinum group iii strain isolated from a human blood culture.a nontoxigenic strain isolated from a fatal human case of bacterial sepsis was identified as a clostridium strain from clostridium botulinum group iii, based on the phenotypic characters and 16s rrna gene sequence, and was found to be related to the mosaic c. botulinum d/c strain according to a multilocus sequence analysis of 5 housekeeping genes.201424088855
the cold-induced two-component system cbo0366/cbo0365 regulates metabolic pathways with novel roles in group i clostridium botulinum atcc 3502 cold tolerance.the two-component system cbo0366/cbo0365 was recently demonstrated to have a role in cold tolerance of group i clostridium botulinum atcc 3502. the mechanisms under its control, ultimately resulting in increased sensitivity to low temperature, are unknown. a transcriptomic analysis with dna microarrays was performed to identify the differences in global gene expression patterns of the wild-type atcc 3502 and a derivative mutant with insertionally inactivated cbo0365 at 37 and 15°c. altogether, 1 ...201424162575
piezoelectric ceramic (pzt) modulates axonal guidance growth of rat cortical neurons via rhoa, rac1, and cdc42 pathways.electrical stimulation is critical for axonal connection, which can stimulate axonal migration and deformation to promote axonal growth in the nervous system. netrin-1, an axonal guidance cue, can also promote axonal guidance growth, but the molecular mechanism of axonal guidance growth under indirect electric stimulation is still unknown. we investigated the molecular mechanism of axonal guidance growth under piezoelectric ceramic lead zirconate titanate (pzt) stimulation in the primary culture ...201424203571
botulism with unusual rapid progression to complete paralysis in a child.botulism is a severe neuroparalytic illness which is difficult to diagnose accurately, especially in children. we report a child with type a botulism intoxication, with very rapid progression to coma-like consciousness and respiratory failure. careful physical examinations led to the suspicion of botulism, and electrophysiologic examinations, including electroencephalogram and repetitive nerve stimulation tests, further supported the diagnosis. hospitalization due to botulism had a great emotion ...201523755946
genomics of clostridium botulinum group iii strains.in clostridium botulinum, the characteristics of type c and d strains are quite different from other types, and they are classified as group iii. they produce c2 binary toxin and c3 exoenzyme in addition to type c and d neurotoxins. two different phages and many plasmids are identified in the organisms. the genes of neurotoxin and c3 exoenzyme are converted from toxigenic strains to non-toxigenic strains by the specific bacteriophages (phages), whereas, the c2 toxin gene is carried by large or s ...201525111022
optimization of peptide substrates for botulinum neurotoxin e improves detection sensitivity in the endopep-ms assay.botulinum neurotoxins (bonts) produced by clostridium botulinum are the most poisonous substances known to humankind. it is essential to have a simple, quick, and sensitive method for the detection and quantification of botulinum toxin in various media, including complex biological matrices. our laboratory has developed a mass spectrometry-based endopep-ms assay that is able to rapidly detect and differentiate all types of bonts by extracting the toxin with specific antibodies and detecting the ...201525232998
historical and current perspectives on clostridium botulinum diversity.for nearly one hundred years, researchers have attempted to categorize botulinum neurotoxin-producing clostridia and the toxins that they produce according to biochemical characterizations, serological comparisons, and genetic analyses. throughout this period the bacteria and their toxins have defied such attempts at categorization. below is a description of both historic and current clostridium botulinum strain and neurotoxin information that illustrates how each new finding has significantly a ...201525312020
mechanisms of food processing and storage-related stress tolerance in clostridium botulinum.vegetative cultures of clostridium botulinum produce the extremely potent botulinum neurotoxin, and may jeopardize the safety of foods unless sufficient measures to prevent growth are applied. minimal food processing relies on combinations of mild treatments, primarily to avoid deterioration of the sensory qualities of the food. tolerance of c. botulinum to minimal food processing is well characterized. however, data on effects of successive treatments on robustness towards further processing is ...201525303833
a case of type b botulism in a pregnant bitch.a two-year-old pregnant gordon setter presented with acute onset of flaccid tetraparesis and respiratory distress. neurological examination revealed diffuse lower motor neuron dysfunction. clostridium botulinum neurotoxin b was isolated from the dog's serum. the dog was hospitalised and received supportive care; respiratory function was monitored but positive-pressure ventilation was not required. recovery was complete within 1 month and parturition occurred without complication 49 days after ad ...201525362862
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