Pathogenicity and virulence of
            <i>Clostridium botulinum</i>

Rawson, Alexander M.; Dempster, Andrew W.; Humphreys, Christopher M.; Minton, Nigel P.

doi:10.1080/21505594.2023.2205251

Cited by 30 publications

(19 citation statements)

References 313 publications

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“…They may come from contaminated soil and dust from nearby construction sites, via the consumption of powdered milk, natural sweeteners, corn syrup, or medicinal herbs. The real impact of infant botulism is likely underestimated worldwide given diagnostic difficulties and the condition’s non-specific presentation ( 12 , 13 ). At the time of the present study, iatrogenic botulism caused by the therapeutic use of BoNT (for the treatment of spasticity, focal dystonia, hemifacial spasm, hyperhydrosis, strabismus, chronic migraine, and cosmetic) was unreported.…”

Section: Discussionmentioning

confidence: 99%

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Exploring the genetic background of the botulism neurotoxin BoNT/B2 in Spain

Valdezate,

Carrasco,

Medina

et al. 2023

Microbiol Spectr

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To determine whether the neurotoxin BoNT/B2 causing botulism in Spain is clonal, the genetic diversity and phylogenetic relationships of Clostridium botulinum from food-borne episodes and infant cases of the condition were explored. The botulinum toxin gene ( bont ) subtype, the variable region of the flagellin gene ( fla VR), and a seven-gene multi-locus sequence type were examined by sequencing 37 BoNT-positive cultures obtained over the period 2010 to 2022. Out of 37 botulism events, 16 food-borne episodes and 16 infant cases were associated with bont/b 2. Eight bont/b 2 alleles were detected [nucleotide distance range 0.0259–0.415%, Hunter and Gaston discrimination index (HGDI) 0.71]. The most common bont/b 2 allele corresponded to that of strain Prevot 25 NCASE and its single and double locus variations (87.5%). Four known fla VR types were identified (HGDI 0.79), along with one previously unknown ( fla VR-15). Sixteen sequence types (STs) (HGDI 0.89) were recorded including seven new STs (ST164–ST170; 10 new alleles) and five new STs (ST171–ST175; with new allele combinations) were also noted. Correlations among some STs and fla VR types were seen. Overall, the present results show that the combined analysis of bont/b 2- fla VR-ST at the nucleotide level could be used to track botulism events in Spain. The neurotoxin BoNT/B2 has largely been responsible for human botulism in Spain. The polymorphism analysis of bont/b2 , fla VR typing, and sequence type determinations, revealed a wide variety of clones to be responsible for human botulism, ruling out a common source of acquisition. IMPORTANCE Botulism, a potentially fatal disease, is classically characterized by a symmetrical descending flaccid paralysis, which if left untreated can lead to respiratory failure and death. Botulinum neurotoxin (BoNT), produced by certain species of Clostridium, is the most potent biological toxin known, and the direct cause of botulism. This study characterizes the acquisition in Spain of two forms of botulism, i.e., food-borne and infant botulism, which are largely caused by the main neurotoxin BoNT/B2. Polymorphism analysis of the bont/b2 gene, typing of the flagellin variable region sequence (flaVR), and multilocus sequence typing, were used to explore the genetic background of Clostridium botulinum group I. To our knowledge, this is the first phylogenetic and typing study of botulism undertaken in Spain.

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Section: Discussionmentioning

confidence: 99%

“…After the disease develops, its treatment is problematic and mortality is high. Treatment includes trivalent or heptavalent equine botulinum antitoxin plus intensive care support, but even available between 5% and 10% of patients with food-borne botulism die ( 1 , 3 , 12 , 13 ).…”

Section: Introductionmentioning

confidence: 99%

Exploring the genetic background of the botulism neurotoxin BoNT/B2 in Spain

Valdezate,

Carrasco,

Medina

et al. 2023

Microbiol Spectr

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“…Clostridium botulinum is a species of bacteria from the Clostridiaceae family, which comprises more than 150 species, of which fewer than 20 are pathogenic [ 7 ]. These bacteria can be classified according to the mode and site of action of their toxins into several groups, among which the following stand out: histotoxic clostridia, enteropathogenic clostridia and producers of enterotoxaemia, as well as neurotoxic clostridia [ 8 ]. This Gram-positive bacillus is characterised by being large in size and having mobility thanks to its peritrichous flagella ( Figure 2 ) [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

The Latent Threat in Wild Birds: Clostridium botulinum

Gutiérrez-Arnal,

Marín

2024

Veterinary Sciences

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Avian botulism caused by Clostridium botulinum emerged in 1910, affecting birds across North America, leading to severe outbreaks exacerbated by climate change, decreasing water levels, and inadequate wastewater management. While deadly for birds, its epidemiological impact on humans and other animals remains limited. Despite its significance, understanding and controlling the disease remain challenging. This review delves into the pathogen’s epidemiology in wild bird populations, exploring the transmission, pathogenicity, clinical symptoms, diagnosis and treatment. The disease’s growing concern in wild birds relates to the bacterium’s adaptability and expansive spread, evident through genetic similarities among strains across countries. Outbreaks are influenced by environmental factors such as temperature and soil characteristics. Wild birds inadvertently transmit the bacterium, perpetuating the cycle through carcasses and flies. Some species suffer severely, while others, like scavengers, show resistance. Understanding disease mechanisms, involving potential toxin ingestion or internal production, remains ongoing. Clinical signs vary, affecting diverse bird orders. Diagnostic methods evolve, with treatment success varying among affected populations. Prevention and surveillance take precedence due to treatment challenges, emphasising population-based strategies and preventive measures to manage the widespread presence of C. botulinum.

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“…Comparative and pan-genome analyses of C. tetani isolates have been conducted ( 13 , 14 ). However, limited data are available regarding C. tetani isolate genomic diversity within specific countries or global regions ( 11 , 12 , 15 , 16 ). To date, C. tetani isolates have been categorized into two clades, clades 1 and 2 ( 14 ), with clade 1 strains being more prevalent globally.…”

Section: Introductionmentioning

confidence: 99%

Comparative pathogenomic analysis reveals a highly tetanus toxin-producing clade of Clostridium tetani isolates in Japan

Shitada,

Sekizuka,

Yamamoto

et al. 2023

mSphere

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Clostridium tetani is the etiological agent of the disease tetanus, resulting in various symptoms, including neck tension, tongue-twisting, a decline in walking ability, and death in severe cases. To date, publicly available genome sequences of C. tetani are limited. C. tetani was isolated from soil in Kumamoto Prefecture, Japan, between 2020 and 2022. Subsequently, bacteriological, biochemical, genetic, and immunological tests were conducted. Among the 46 soil sampling sites, 151 C . tetani strains were isolated from 33 sites, with a 71.7% positivity rate. Comparative genomic analysis subdivided clade 1 into clades 1-1, 1-2, and 1-3. The enzyme-linked immunosorbent assay revealed that partial clade 1-3 strains produced over sevenfold more tetanus neurotoxin (TeNT) than the reference strain (first isolate of C. tetani KHSU-154301-001). RNA-Seq analysis supported this elevated tetanus toxin tetX gene expression. Additionally, tetX -negative strains were isolated from the clade, indicating that TeNT may not be essential for ensuring the survival of their offspring without its representative toxin-causing tetanus. Five strains acquired the tetracycline resistance gene tet (M) in the tetX plasmid, resulting in significantly reduced susceptibility to tetracycline. In conclusion, although we investigated C. tetani isolates from a specific region of the Kumamoto Prefecture, we demonstrated that these isolates exhibit variable genomic features, toxin productivity, and substantial acquired antimicrobial resistance. These findings indicate that multiple C. tetani lineages have successfully adapted to the soil in Japan, as evidenced by the additional genome information and toxin productivity assays in this study. IMPORTANCE C. tetani is a spore-forming, anaerobic bacterium that produces a toxin causing muscle stiffness and paralysis. Tetanus is preventable with the toxoid vaccine, but it remains a significant public health threat in regions with low vaccine coverage. However, there are relatively few isolates and limited genomic information available worldwide. In Japan, about 100 cases are reported each year, but there have been no nationwide surveys of isolates, and no genomic information from Japanese isolates has been published. In our study, we analyzed the genomes of 151 strains from a limited survey of soil in Kumamoto, Japan. Our findings revealed a high degree of genetic diversity, and we also identified a subset of strains that produced significantly more toxin, which provides new insights into the pathogenesis of tetanus. Our findings lay the foundation for future studies to investigate the distribution and evolution of C. tetani in Japan and neighboring countries.

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Pathogenicity and virulence of Clostridium botulinum

Cited by 30 publications

References 313 publications

Exploring the genetic background of the botulism neurotoxin BoNT/B2 in Spain

Exploring the genetic background of the botulism neurotoxin BoNT/B2 in Spain

The Latent Threat in Wild Birds: Clostridium botulinum

Comparative pathogenomic analysis reveals a highly tetanus toxin-producing clade of Clostridium tetani isolates in Japan

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