Dual Toxin-Producing Strain of
            <i>Clostridium botulinum</i>
            Type Bf Isolated from a California Patient with Infant Botulism

Barash, Jason R.; Arnon, Stephen S.

doi:10.1128/jcm.42.4.1713-1715.2004

Cited by 50 publications

(32 citation statements)

References 7 publications

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“…Seven different toxinotypes (A-G) can be distinguished and some (B, E and F) are present in more than one of the BoNT-producing Clostridium groups. 4 Also, some strains are bivalent and have two bont gene clusters of different toxinotypes 5,6 and some have chimerical toxinotypes (C/D and D/C). 7,8 This variable distribution of bont gene clusters in the groups suggests that horizontal movements have taken place on several occasions.…”

Section: Horizontal Gene Transfer Of Toxin Genes In Clostridium Botulmentioning

confidence: 99%

Horizontal gene transfer of toxin genes inClostridium botulinum

Skarin

Segerman

2011

Mobile Genetic Elements

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Section: Horizontal Gene Transfer Of Toxin Genes In Clostridium Botulmentioning

confidence: 99%

Horizontal gene transfer of toxin genes inClostridium botulinum

Skarin

Segerman

2011

Mobile Genetic Elements

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“…The dichain is thought to be the active form of the toxin (1). In the United States, there are ∼200 cases of human botulism each year, due to ingestion of toxin-contaminated food, wound infections, or colonization of the intestinal tract by C. botulinum (5)(6)(7). However, much of the current interest in BoNTs 1 stems from their use as tools in research on the mechanisms of neurotransmission (1,8,9), an ever-expanding number of applications in the treatment of human muscle dysfunctions (10)(11)(12)(13), and their potential for use as bioterrorist weapons (14).…”

mentioning

confidence: 99%

Botulinum Neurotoxin Serotype F: Identification of Substrate Recognition Requirements and Development of Inhibitors with Low Nanomolar Affinity

Schmidt

Stafford

2005

Biochemistry

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Botulinum neurotoxins (BoNTs A-G) are zinc metalloendoproteases that exhibit extraordinary specificities for proteins involved in neurotransmitter release. In view of the extreme toxicities of these molecules, their applications in human medicine, and potential for misuse, it is of considerable importance to elucidate the mechanisms underlying substrate recognition and to develop inhibitors, with the ultimate goal of obtaining anti-botulinum drugs. We synthesized peptides based on vesicle-associated membrane protein (VAMP) to investigate the substrate requirements of BoNT F, which cleaves VAMP between residues Q58 and K59. The minimum substrate was a peptide containing VAMP residues 32-65, which includes only one of the two VAMP structural motifs thought to be required for botulinum substrate recognition. BoNT F exhibited a strict requirement for residues D57 (P 2 ), K59 (P 1 ′), and L60 (P 2 ′), but peptides containing substitutions for R56 (P 3 ), Q58 (P 1 ), and S61 (P 3 ′) were cleaved. Therefore, the P 2 , P 1 ′, and P 2 ′ residues of VAMP are of paramount importance for BoNT F substrate recognition near the scissile bond. K i values of uncleavable analogues were similar to K m values of the substrate, suggesting that substrate discrimination occurs at the cleavage step, not at the initial binding step. We then synthesized inhibitors of BoNT F that incorporated D-cysteine in place of glutamine 58, exhibited K i values of 1-2 nM, and required binding groups on the N-terminal but not the C-terminal side of the zinc ligand. The latter characteristic distinguishes BoNT F from other zinc metalloendoproteases, including BoNTs A and B.The clostridial neurotoxins consist of tetanus toxin, secreted by Clostridium tetani, and the seven serologically distinct botulinum toxins, designated types A-G, produced by various strains of Clostridium botulinum, Clostridium baratii, and Clostridium butyricum (1-3). They are the most toxic substances known (4). Each neurotoxin is synthesized as a single-chain protein with an M r of ∼150000. Endogenous proteases then act to produce the dichain structure, consisting of an M r ∼ 100 000 heavy chain and an M r ∼ 50 000 light chain, covalently linked by a disulfide bond. The dichain is thought to be the active form of the toxin (1). In the United States, there are ∼200 cases of human botulism each year, due to ingestion of toxin-contaminated food, wound infections, or colonization of the intestinal tract by C. botulinum (5-7). However, much of the current interest in BoNTs 1 stems from their use as tools in research on the mechanisms of neurotransmission (1,8,9), an ever-expanding number of applications in the treatment of human muscle dysfunctions (10-13), and their potential for use as bioterrorist weapons (14).Intoxication resulting in the flaccid paralysis of botulism or the spastic paralysis of tetanus has been described as a four-step process, consisting of (1) toxin binding to specific receptors on neurons, (2) receptor-mediated toxin endocytosis, (3) translocation th...

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“…Botulinum neurotoxins (BoNTs) are the most poisonous substances known and are classified into seven serologically distinct groups (serotypes A to G) (Hatheway, 1995). Most strains produce only one serotype of BoNT, but some produce more than one toxin serotype, including Ab, Ba, Af and Bf (Barash & Arnon, 2004;Gimenez & Gimenez, 1993;Santos-Buelga et al, 1998), whereby the highest quantity of BoNT produced is designated by the upper-case letter. Many strains also contain unexpressed (silent) BoNT genes, where the silent gene is shown in parentheses, e.g.…”

Section: Introductionmentioning

confidence: 99%