An inactivated bacterium (paraprobiotic) expressing Bacillus thuringiensis Cry5B as a therapeutic for Ascaris and Parascaris spp. infections in large animals

Urban, Joseph F.; Nielsen, Martin K.; Gazzola, David; Xie, Yue; Beshah, Ethiopia; Hu, Yan; Li, Hanchen; Rus, Florentina; Flanagan, Kelly; Draper, Austin; Vakalapudi, Sridhar; Li, Robert W.; Ostroff, Gary R.; Aroian, Raffi V.

doi:10.1016/j.onehlt.2021.100241

Cited by 12 publications

(19 citation statements)

References 47 publications

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“…Ascaris lumbricoides or intestinal large roundworm is one of the most common parasites of humans worldwide and highly related to, if not the same species as, Ascaris suum, the dominant intestinal nematode parasite of pigs (33)(34)(35). We have reported on an immunodeficient mouse-model for Ascaris suum in which A. suum eggs gavaged into Th2-deficient mice develop into early intestinal parasitic L4 stage, which can then be used for intestinal Ascaris studies in rodents (17). Here, we tested Cry5B PCC against this experimental infection (Figure 6).…”

Section: Cry5b Pcc Is Effective Against Ascarids Including Scale Up A...mentioning

confidence: 99%

“…We have previously demonstrated that Cry5B is effective in foals against infestations of Parascaris spp., a critical and potentially lethal parasite of young horses related to human Ascaris (17,36). We performed a pilot study in foals infected with Parascaris spp.…”

Section: Cry5b Pcc Is Effective Against Ascarids Including Scale Up A...mentioning

confidence: 99%

“…This safety factor has played an important role in the adoption and expansion of use of Cry proteins, including as expressed proteins in transgenic crops, e.g., to produce insect-resistant corn and cotton varieties that are now planted in >108 million hectares worldwide (10). In addition to targeting insects, some Bt Cry proteins also target nematodes, including intestinal parasites of humans, dogs, horses, sheep, and pigs and parasites of plants (11)(12)(13)(14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

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Purified cytosolic crystals from Bacillus thuringiensis as a novel active pharmaceutical ingredient (API)

Chicca

Cazeault

Rus

et al. 2022

Preprint

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Bacillus thuringiensis or Bt is a Gram-positive soil bacterium, widely and safely applied in the environment as an insecticide for combatting insect pests that damage crops and vector diseases. Dominant active ingredients made by Bt are insect-killing crystal (Cry) proteins released as crystalline inclusions upon bacterial sporulation. Some Bt Cry proteins, e.g., Cry5B, target nematodes (roundworms) and show exceptional promise as anthelmintics (cures for parasitic nematode diseases). We have recently described IBaCC (for Inactivated Bacteria with Cytosolic Crystal(s)) in which bioactive Bt Cry crystals (containing Cry5B) are fully contained within the cytosol of dead bacterial ghosts. Here we demonstrate that these IBaCC-trapped Cry5B crystals can be liberated and purified away from cellular constituents yielding Purified Cytosolic Crystals (PCC). Cry5B PCC contains ~95% Cry5B protein out of the total protein content. Cry5B PCC is highly bioactive against parasitic nematode larvae and adults in vitro. Cry5B PCC is also highly active in vivo against experimental human hookworm and Ascaris infections in rodents. The process was scaled up to the 100 liter scale to produce PCC for a pilot study to treat two foals infected with the Ascarid, Parascaris spp. Single dose Cry5B PCC brought the fecal egg counts of both foals to zero. These studies describe the process for the scalable production of purified Bt crystals and define a new active pharmaceutical ingredient form of Bt Cry proteins.

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Section: Cry5b Pcc Is Effective Against Ascarids Including Scale Up A...mentioning

confidence: 99%

Section: Cry5b Pcc Is Effective Against Ascarids Including Scale Up A...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Purified cytosolic crystals from Bacillus thuringiensis as a novel active pharmaceutical ingredient (API)

Chicca

Cazeault

Rus

et al. 2022

Preprint

Self Cite

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“…The paraprobiotic intoxicated A. suum larvae in vitro and was highly effective against intestinal A. suum infections in a mouse model. In pigs, a single oral dose of this paraprobiotic reduced the parasite burden by 96% during A. suum infections ( Urban et al, 2021 ). This strategy results in an attractive alternative for the control other helminth infections.…”

Section: Probiotics As Complement/treatment Against Helminth Infectionsmentioning

confidence: 99%

Searching for the one(s): Using Probiotics as Anthelmintic Treatments

Saracino¹,

Vila²,

Baldi³

et al. 2021

Front. Pharmacol.

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Helminths are a major health concern as over one billion people are infected worldwide and, despite the multiple efforts made, there is still no effective human vaccine against them. The most important drugs used nowadays to control helminth infections belong to the benzimidazoles, imidazothiazoles (levamisole) and macrocyclic lactones (avermectins and milbemycins) families. However, in the last 20 years, many publications have revealed increasing anthelmintic resistance in livestock which is both an economical and a potential health problem, even though very few have reported similar findings in human populations. To deal with this worrying limitation of anthelmintic drugs, alternative treatments based on plant extracts or probiotics have been developed. Probiotics are defined by the Food and Agriculture Organization as live microorganisms, which, when consumed in adequate amounts, confer a health benefit to the host. It has been proven that probiotic microbes have the ability to exert an immunomodulatory effect both at the mucosa and the systemic level. The immune response against gastrointestinal helminths is characterized as a type 2 response, with high IgE levels, increased numbers and/or activity of Th2 cells, type 2 innate lymphoid cells, eosinophils, basophils, mast cells, and alternatively activated macrophages. The oral administration of probiotics may contribute to controlling gastrointestinal helminth infections since it has been demonstrated that these microorganisms stimulate dendritic cells to elicit a type 2 or regulatory immune response, among other effects on the host immune system. Here we review the current knowledge about the use of probiotic bacteria as anthelmintic therapy or as a complement to traditional anthelmintic treatments. Considering all research papers reviewed, we may conclude that the effect generated by probiotics on helminth infection depends not only on the parasite species, their stage and localization but also on the administration scheme.

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“…Dentre as bactérias do gênero Bacillus, B. thuringiensis talvez seja a mais explorada, tanto no âmbito da medicina humana, quanto na veterinária e agronomia (RAMALAKSHMI et al, 2020;URBAN et al, 2021). Esta bactéria age contra nematoides por meio de cristais parasporais e proteínas Cry, que degradam as células intestinais do helminto .…”

Section: Introductionunclassified

Avaliação do potencial nematicida in vitro de formulações comerciais à base de Bacillus spp

Ferreira¹

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Animais da raça Gir no Brasil e no mundo sofrem frequentemente com otite parasitária externa. Esta doença é causada principalmente por nematoides do gênero Metarhabditis spp. e pode causar desconforto, secreções purulentas, sinais neurológicos e morte dos animais, além de queda no desempenho produtivo e reprodutivo no rebanho. Diferentes bactérias do gênero Bacillus já possuem ação consolidada no controle de pragas agrícolas e algumas já são comercialmente utilizadas. O objetivo do presente estudo foi avaliar a eficácia de produtos comerciais A, B e C, compostos por Bacillus spp. no controle in vitro de Meterhabditis sp., além dos modelos Panagrellus redivivus e Caenorhabditis elegans. O produto A é constituído por Bacillus subtilis QST-713, o produto B de B. thuringiensis CCT 1306 e o produto C trata-se de uma associação entre B. subtilis CCTB 04, B. pumilus CCTB 05 e Bacillus amyloliquefaciens CCTB 09. Quando testados contra C. elegans, cepa N2, o produto A apresentou DL50 mínima de 0,5 ml/L, dentro de 24h e manteve-se altamente eficaz mesmo quando autoclavado ou diluído em PBS a 5% da concentração original. O produto B apresentou DL50 de 3,1 ml/L, dentro de 24h e manteve a grande eficácia quando autoclavado diluído em concentrações a partir de 10%. O produto C apresentou DL50 169 ml/L, obtida em 48h, tempo máximo que delongou este experimento e apresentou alta eficácia apenas quando foi testado sem ser diluído, autoclavado ou não. Já nos ensaios com P. redivivus, o produto A apresentou DL50 mínima de 47 ml/L, observada em 96h e obteve alta eficácia a partir de quando diluído a 25% e mesmo quando autoclavado em concentração máxima. O produto B, obteve DL50 mínima de 165 ml/L, obtida em 120h, tempo máximo que delongou este experimento, e manteve alta eficácia a partir de quando diluído a 50% e quando autoclavado em concentração máxima. O produto C não obteve eficácia significativa. No caso de Metarhabditis sp., o produto A apresentou DL50 mínima de 5 ml/L em apenas 24h e permaneceu com máxima eficácia a partir da diluição de 5%, a menor testada, e após autoclavado em concentração máxima. O produto B apresentou DL50 mínima de 2 ml/L em 24h e também apresentou máxima eficácia a partir da diluição de 5% e no produto autoclavado em concentração máxima. O produto C também não apresentou eficácia significativa no caso de Metarhabditis spp. A partir destes resultados, podemos concluir que os produtos A e B podem ser considerados eficientes nematicidas mesmo diluídos ou autoclavados, não só contra Metarhabditis spp., mas também contra outras espécies de nematoides. Apesar do produto C não ter se mostrado eficaz contra Metarhabditis sp. e ter se mostrado, em geral, com menor potencial nematicida, ele não pode ser completamente descartado para avaliação de nematotoxicidade em outras espécies de importância veterinária. Palavras-chave: Controle biológico. Nematoides. Bacillus spp. Metarhabditis spp.

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An inactivated bacterium (paraprobiotic) expressing Bacillus thuringiensis Cry5B as a therapeutic for Ascaris and Parascaris spp. infections in large animals

Cited by 12 publications

References 47 publications

Purified cytosolic crystals from Bacillus thuringiensis as a novel active pharmaceutical ingredient (API)

Purified cytosolic crystals from Bacillus thuringiensis as a novel active pharmaceutical ingredient (API)

Searching for the one(s): Using Probiotics as Anthelmintic Treatments

Avaliação do potencial nematicida in vitro de formulações comerciais à base de Bacillus spp

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