Publications

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 ...	2014	24463972
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 ...	2014	24468429
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 ...	2014	24472509
[bioterrorism and pathogenic microorganisms].	in recent years the use of pathogenic microorganisms in acts of bioterrorism has been the subject of major concern in many countries. this paper presents a possible application of viruses and bacteria for warfare and terrorist purposes, as well as a laboratory diagnosis to identify those agents. the viruses of smallpox (orthopoxvirus), of hemorrhagic fever and those belonging to filovirus have been highlighted, inter alia, as agents of human infection with bioterrorist intent. among the bacteria ...	2013	24473660
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 ...	2014	24475015
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 ...	2014	24488164
development of neutralizing scfv-fc against botulinum neurotoxin a light chain from a macaque immune library.	botulinum toxins (bonts) are among the most toxic substances on earth, with serotype a toxin being the most toxic substance known. they are responsible for human botulism, a disease characterized by flaccid muscle paralysis that occurs naturally through food poisoning or the colonization of the gastrointestinal tract by bont-producing clostridia. bont has been classified as a category a agent by the centers for disease control, and it is one of six agents with the highest potential risk of use a ...	2014	24492304
outbreak of type c botulism in birds and mammals in the emilia romagna region, northern italy.	over a 7-day period beginning 8 august 2011, a large number of wild birds of several species were found dead or with neurologic clinical signs along the shore of crostolo stream, in the emilia romagna region, italy. twenty-eight mallards (anas platyrhynchos), two hooded crows (corvus corone cornix), and three coypus (myocastor coypus) were found moribund on the crostolo stream bank, collected, and sent to istituto zooprofilattico sperimentale della lombardia e dell'emilia romagna, reggio emilia ...	2013	24502738
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 ...	2014	24506443
subtilin and the spores of clostridium botulinum.		1952	24541795
effect of some antibiotics on clostridium botulinum.		1953	24542418
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.	2014	24558013
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 ...	2014	24560879
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 ...	2014	24580639
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 ...	2014	24582943
[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 ...	2014	24584800
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 ...	2014	24584821
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 ...	2014	24587151
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 ...	2014	24598930
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 ...	2014	24600582
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 ...	2014	24605815
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 ...	2014	24615939
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 ...	2014	24621137
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 ...	2014	24631690
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 ...	2014	24632257
biosynthesis of a thiamin antivitamin in clostridium botulinum.	bacimethrin-derived 2'-methoxythiamin pyrophosphate inhibits microbial growth by disrupting metabolic pathways dependent on thiamin-utilizing enzymes. this study describes the discovery of the bacimethrin biosynthetic gene cluster of clostridium botulinum a atcc 19397 and in vitro reconstitution of bacimethrin biosynthesis from cytidine 5'-monophosphate.	2014	24654570
camelid-derived heavy-chain nanobody against clostridium botulinum neurotoxin e in pichia pastoris.	botulinum neurotoxins (bonts) result in severe and often fatal disease, botulism. common remedial measures such as equine antitoxin and human botulism immunoglobulin in turn are problematic and time-consuming. therefore, diagnosis and therapy of bonts are vital. the variable domain of heavy-chain antibodies (vhh) has unique features, such as the ability to identify and bind specifically to target epitopes and ease of production in bacteria and yeast. the pichia pastoris is suitable for expressio ...	2017	24673401
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 ...	2014	24678189
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 ...	2014	24709046
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.	2014	24724492
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 ...	2014	24747040
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.	2014	24766494
[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 ...	2014	24768073
[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.	2014	24791561
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 ...	2014	24795377
clostridium botulinum toxin statement from the director of the california department of public health.		2014	24808389
clarification regarding novel clostridium botulinum toxin.		2014	24808390
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 ...	2014	24837790
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 ...	2014	24853378
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 ...	2014	24867833
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 ...	2014	24892033
innate immune sensing of bacterial modifications of rho gtpases by the pyrin inflammasome.	cytosolic inflammasome complexes mediated by a pattern recognition receptor (prr) defend against pathogen infection by activating caspase 1. pyrin, a candidate prr, can bind to the inflammasome adaptor asc to form a caspase 1-activating complex. mutations in the pyrin-encoding gene, mefv, cause a human autoinflammatory disease known as familial mediterranean fever. despite important roles in immunity and disease, the physiological function of pyrin remains unknown. here we show that pyrin mediat ...	2014	24919149
molecular epidemiology of infant botulism in california and elsewhere, 1976-2010.	infant botulism (ib), first identified in california in 1976, results from clostridium botulinum spores that germinate, multiply, and produce botulinum neurotoxin (bont) in the immature intestine. from 1976 to 2010 we created an archive of 1090 bont-producing isolates consisting of 1012 ib patient (10 outpatient, 985 hospitalized, 17 sudden death), 25 food, 18 dust/soils, and 35 other strains.	2014	24924163
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 ...	2014	24928875
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 ...	2014	24930432
cationic pamam dendrimers as pore-blocking binary toxin inhibitors.	dendrimers are unique highly branched macromolecules with numerous groundbreaking biomedical applications under development. here we identified poly(amido amine) (pamam) dendrimers as novel blockers for the pore-forming b components of the binary anthrax toxin (pa63) and clostridium botulinum c2 toxin (c2iia). these pores are essential for delivery of the enzymatic a components of the internalized toxins from endosomes into the cytosol of target cells. we demonstrate that at low μm concentration ...	2014	24954629
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 ...	2014	24961027
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 ...	2014	24966853
vimentin mediates uptake of c3 exoenzyme.	clostridium botulinum c3 exoenzyme (c3) selectively inactivates rhoa/b/c gtpases by adp-ribosylation. based on this substrate specificity c3 is a well-established tool in cell biology. c3 is taken up by eukaryotic cells although lacking an uptake and translocation domain. based on different approaches vimentin was identified as membranous c3-interaction partner by mass spectrometry. vimentin in fact was partly localized at the outer surface of hippocampal ht22 cells and j744a.1 macrophages. doma ...	2014	24967582
detection of pathogenic clostridia in biogas plant wastes.	as the number of biogas plants has grown rapidly in the last decade, the amount of potentially contaminated wastes with pathogenic clostridium spp. has increased as well. this study reports the results from examining 203 biogas plant wastes (bgws). the following clostridium spp. with different frequencies could be isolated via a new enrichment medium (krüne medium) and detected by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (maldi-tof ms): clostridium perfringens ...	2015	24984829
hidradenitis suppurativa treated with clostridium botulinum toxin a.		2014	24986398
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/ ...	2014	24997242
tailored cyclodextrin pore blocker protects mammalian cells from clostridium difficile binary toxin cdt.	some clostridium difficile strains produce, in addition to toxins a and b, the binary toxin clostridium difficile transferase (cdt), which adp-ribosylates actin and may contribute to the hypervirulence of these strains. the separate binding and translocation component cdtb mediates transport of the enzyme component cdta into mammalian target cells. cdtb binds to its receptor on the cell surface, cdta assembles and cdtb/cdta complexes are internalised. in acidic endosomes, cdtb mediates the deliv ...	2014	25029374
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 ...	2014	25031122
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 ...	2014	25041523
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.	2014	25054790
cyclophilin-facilitated membrane translocation as pharmacological target to prevent intoxication of mammalian cells by binary clostridial actin adp-ribosylated toxins.	clostridium botulinum c2 toxin, clostridium perfringens iota toxin and clostridium difficile cdt belong to the family of binary actin adp-ribosylating toxins and are composed of a binding/translocation component and a separate enzyme component. the enzyme components adp-ribosylate g-actin in the cytosol of target cells resulting in depolymerization of f-actin, cell rounding and cell death. the binding/translocation components bind to their cell receptors and form complexes with the respective en ...	2015	25058685
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 ...	2014	25060982
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 ...	2014	25062018
being prepared: bioterrorism and mass prophylaxis: part i.	bioterrorism presents a real and omnipresent risk to public health throughout the world. more than 30 biological agents have been identified as possessing the potential to be deployed in a bioterrorist attack. those that have been determined to be of the greatest concern and possess the greatest potential of use in this arena are known as the category a agents: bacillus anthracis (anthrax); variola major (smallpox); yersinia pestis (plague); francisella tularensis (tularemia); viral hemorrhagic ...	2014	25076398
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 ...	2014	25079304
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. ...	2014	25079343
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 ...	2014	25084657
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 ...	2014	25084658
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 ...	2014	25107978
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 ...	2015	25111022
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 ...	2014	25149145
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 ...	2014	25157243
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 ...	2014	25175400
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 ...	2014	25188279
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 ...	2014	25192986
clostridium and bacillus binary enterotoxins: bad for the bowels, and eukaryotic being.	some pathogenic spore-forming bacilli employ a binary protein mechanism for intoxicating the intestinal tracts of insects, animals, and humans. these gram-positive bacteria and their toxins include clostridium botulinum (c2 toxin), clostridium difficile (c. difficile toxin or cdt), clostridium perfringens (ι-toxin and binary enterotoxin, or bec), clostridium spiroforme (c. spiroforme toxin or cst), as well as bacillus cereus (vegetative insecticidal protein or vip). these gut-acting proteins for ...	2014	25198129
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. ...	2014	25210747
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 ...	2014	25230330
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 ...	2015	25232998
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 ...	2014	25239905
botulinum neurotoxin subtype a4 originating from nontoxigenic clostridium botulinum.		2014	25239910
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 ...	2014	25254374
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 ...	2014	25277214
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 ...	2014	25281376
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 ...	2015	25303833
immunological function of familial mediterranean fever disease protein pyrin.	pyrin, encoded by mefv gene, is conserved in humans and mice. mutations in the mefv gene are associated with the human autoinflammatory disease familial mediterranean fever (fmf). pyrin can interact with the inflammasome adaptor asc and induce inflammatory caspase-1 activation in monocytic cells, but the physiological function of pyrin has been unknown for many years. here we summarize previous studies of pyrin function under the context of fmf and immunity, and discuss a recent study demonstrat ...	2014	25307949
infant botulism: is there an association with thiamine deficiency?	infant botulism is an acute life-threatening condition and diagnosis is frequently delayed. therefore, the best time window to administer specific antibodies, at present the only etiology-based therapy, is often missed, entailing long periods of hospitalization in the picu. here we present a 3-month-old boy with infant botulism and respiratory failure, who quickly and favorably responded to thiamine supplementation. from the feces we isolated clostridium botulinum serotype a2. in addition to pro ...	2014	25311602
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 ...	2015	25312020
climate change and infectious diseases in the arctic: establishment of a circumpolar working group.	the arctic, even more so than other parts of the world, has warmed substantially over the past few decades. temperature and humidity influence the rate of development, survival and reproduction of pathogens and thus the incidence and prevalence of many infectious diseases. higher temperatures may also allow infected host species to survive winters in larger numbers, increase the population size and expand their habitat range. the impact of these changes on human disease in the arctic has not bee ...	2014	25317383
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 ...	2014	25335884
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 ...	2014	25336912
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 ...	2014	25340348
being prepared: bioterrorism and mass prophylaxis: part ii.	although several biological agents have been recognized as presenting a significant threat to public health if used in a bioterrorist attack, those that are of greatest importance are known as the category a agents: bacillus anthracis (anthrax); variola major (smallpox); yersinia pestis (plague); francisella tularensis (tularemia); ribonucleic acid viruses (hemorrhagic fevers); and clostridium botulinum (botulism toxin). in the previous issue, part i of this review focused on the clinical presen ...	2014	25356890
immunoprecipitation of native botulinum neurotoxin complexes from clostridium botulinum subtype a strains.	botulinum neurotoxins (bonts) naturally exist as components of protein complexes containing nontoxic proteins. the nontoxic proteins impart stability of bonts in the gastrointestinal tract and during purification and handling. the two primary neurotoxin complexes (tcs) are (i) tc1, consisting of bont, nontoxin-nonhemagglutinin (ntnh), and hemagglutinins (has), and (ii) tc2, consisting of bont and ntnh (and possibly orfx proteins). in this study, bont/a subtypes a1, a2, a3, and a5 were examined f ...	2015	25362065
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 ...	2015	25362862
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).	2014	25377702
the influence of glyphosate on the microbiota and production of botulinum neurotoxin during ruminal fermentation.	the aim of the present study is to investigate the impact of glyphosate on the microbiota and on the botulinum neurotoxin (bont) expression during in vitro ruminal fermentation. this study was conducted using two daisy(ii)-incubators with four ventilated incubation vessels filled with rumen fluid of a 4-year-old non-lactating holstein-friesian cow. two hundred milliliter rumen fluid and 800 ml buffer solution were used with six filter bags containing 500 mg concentrated feed or crude fiber-enric ...	2015	25407376
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 ...	2014	25408485
gorilla gorilla gorilla gut: a potential reservoir of pathogenic bacteria as revealed using culturomics and molecular tools.	wild apes are considered to be the most serious reservoir and source of zoonoses. however, little data are available about the gut microbiota and pathogenic bacteria in gorillas. for this propose, a total of 48 fecal samples obtained from 21 gorilla gorilla gorilla individuals (as revealed via microsatellite analysis) were screened for human bacterial pathogens using culturomics and molecular techniques. by applying culturomics to one index gorilla and using specific media supplemented by plants ...	2014	25417711
an atypical outbreak of food-borne botulism due to clostridium botulinum types b and e from ham.	an outbreak of human botulism was due to consumption of ham containing botulinum neurotoxins b and e. a clostridium botulinum type e strain isolated from ham was assigned to a new subtype (e12) based on bont/e gene sequencing and belongs to a new multilocus sequence subtype, as analyzed by whole-genome sequencing.	2015	25428161
characterisation of non-toxigenic clostridium spp. strains, to use as surrogates for non-proteolytic clostridium botulinum in chilled food challenge testing.	under many of the conditions studied, a two-strain cocktail of non-toxigenic clostridium spp. was found to be suitable as a surrogate for non-proteolytic clostridium botulinum, and has the potential for use in chilled food challenge tests measuring growth. non-toxigenic surrogates could also be used in thermal process screening studies.	2015	25433276
probabilistic exposure assessment model to estimate aseptic-uht product failure rate.	aseptic-ultra-high-temperature (uht) products are manufactured to be free of microorganisms capable of growing in the food at normal non-refrigerated conditions at which the food is likely to be held during manufacture, distribution and storage. two important phases within the process are widely recognised as critical in controlling microbial contamination: the sterilisation steps and the following aseptic steps. of the microbial hazards, the pathogen spore formers clostridium botulinum and baci ...	2015	25440556
genomes, neurotoxins and biology of clostridium botulinum group i and group ii.	recent developments in whole genome sequencing have made a substantial contribution to understanding the genomes, neurotoxins and biology of clostridium botulinum group i (proteolytic c. botulinum) and c. botulinum group ii (non-proteolytic c. botulinum). two different approaches are used to study genomics in these bacteria; comparative whole genome microarrays and direct comparison of complete genome dna sequences. the properties of the different types of neurotoxin formed, and different neurot ...	2015	25445012
two-family outbreak of botulism associated with the consumption of smoked ribs in sichuan province, china.	on september 22, 2013, two patients from sichuan province, china presented with symptoms of food-borne botulism, a rare but fatal illness caused by the consumption of foods containing clostridium botulinum neurotoxins.	2015	25448333