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Biron, Éric

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Biron

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Éric

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Université Laval. Faculté de pharmacie

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ncf11849118

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Bacteriocins as a new generation of antimicrobials : toxicity aspects and regulations

2020-09-02, Ben Said, Laila, Biron, Éric, Soltani, Samira, Gaudreau, Hélène, Fliss, Ismaïl, Bédard, François, Hammami, Riadh

In recent decades, bacteriocins have received substantial attention as antimicrobial compounds. Although bacteriocins have been predominantly exploited as food preservatives, they are now receiving increased attention as potential clinical antimicrobials and as possible immune-modulating agents. Infections caused by antibiotic-resistant bacteria have been declared as a global threat to public health. Bacteriocins represent a potential solution to this worldwide threat due to their broad- or narrow-spectrum activity against antibiotic-resistant bacteria. Notably, despite their role in food safety as natural alternatives to chemical preservatives, nisin remains the only bacteriocin legally approved by regulatory agencies as a food preservative. Moreover, insufficient data on the safety and toxicity of bacteriocins represent a barrier against the more widespread use of bacteriocins by the food and medical industry. Here, we focus on the most recent trends relating to the application of bacteriocins, their toxicity and impacts.

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Synthesis and biological evaluation of novel 1,4-benzodiazepin-3-one derivatives as potential antitumor agents against prostate cancer

2021-07-21, Biron, Éric, Gobeil, Stéphane, Vézina-Dawod, Simon, Gerber, Nicolas, Guay, Louis-David, Perreault, Martin

A novel tumor suppressing agent was discovered against PC-3 prostate cancer cells from the screening of a 1,4-benzodiazepin-3-one library. In this study, 96 highly diversified 2,4,5- trisubstituted 1,4-benzodiazepin-3-one derivatives were prepared by a two-step approach using sequential Ugi multicomponent reaction and simultaneous deprotection and cyclization to afford pure compounds bearing a wide variety of substituents. The most promising compound showed a potent and selective antiproliferative activity against prostate cancer cell line PC-3 (GI₅₀ = 10.2 µM), but had no effect on LNCAP, LAPC4 and DU145 cell lines. The compound was initially prepared as a mixture of two diastereomers and after their separation by HPLC, similar antiproliferative activities against PC-3 cells were observed for both diastereomers (2S,5S: GI₅₀ = 10.8 µM and 2S,5R: GI₅₀ = 7.0 µM). Additionally, both diastereomers showed comparable stability profiles after incubation with human liver microsomes. Finally, in vivo evaluation of the hit compound with the chick chorioallantoïc membrane xenograft assay revealed a good toxicity profile and significant antitumor activity after intravenous injection.

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Insights in the development and uses of alternatives to antibiotic growth promoters in poultry and swine production

2022-06-02, Biron, Éric, Rahman, Md Ramim Tanver, Fliss, Ismaïl

The overuse and misuse of antibiotics has contributed to the rise and spread of multidrugresistant bacteria. To address this global public health threat, many countries have restricted the use of antibiotics as growth promoters and promoted the development of alternatives to antibiotics in human and veterinary medicine and animal farming. In food-animal production, acidifiers, bacteriophages, enzymes, phytochemicals, probiotics, prebiotics, and antimicrobial peptides have shown hallmarks as alternatives to antibiotics. This review reports the current state of these alternatives as growth-promoting factors for poultry and swine production and describes their mode of action. Recent findings on their usefulness and the factors that presently hinder their broader use in animal food production are identified by SWOT (strength, weakness, opportunity, and threat) analysis. The potential for resistance development as well as co- and cross-resistance with currently used antibiotics is also discussed. Using predetermined keywords, we searched specialized databases including Scopus, Web of Science, and Google Scholar. Antibiotic resistance cannot be stopped, but its spreading can certainly be hindered or delayed with the development of more alternatives with innovative modes of action and a wise and careful use of antimicrobials in a One Health approach.

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Bacteriocin-based synergetic consortia : a promising strategy to enhance antimicrobial activity and broaden the spectrum of inhibition

2022-02-16, Ben Said, Laila, Biron, Éric, Soltani, Samira, Fliss, Ismaïl, Subirade, Muriel

Bacteria-derived natural antimicrobial compounds such as bacteriocins, reruterin, and organic acids have recently received substantial attention as food preservatives or therapeutic alternatives in human or animal sectors. This study aimed to evaluate the antimicrobial activity of different bacteria-derived antimicrobials, alone or in combination, against a large panel of Gram-negative and Gram-positive bacteria. Bacteriocins, including microcin J25, pediocin PA-1, nisin Z, and reuterin, were investigated alone or in combination with lactic acid and citric acid, using a checkerboard assay. Concentrations were selected based on predetermined MICs against Salmonella enterica subsp. enterica serovar Newport ATCC 6962 and Listeria ivanovii HPB28 as Gram-negative and Gram-positive indicator strains, respectively. The results demonstrated that the combination of microcin J25 + citric acid + lactic acid; microcin J25 + reuterin + citric acid; and microcin J25 + reuterin + lactic acid tested against S. Newport ATCC 6962 showed synergistic effects (FIC index = 0.5). Moreover, a combination of pediocin PA-1 + citric acid + lactic acid; and reuterin + citric acid + lactic acid against L. ivanovii HPB28 showed a partially synergistic interactions (FIC index = 0.75). Nisin Z exerted a partially synergistic effect in combination with acids (FIC index = 0.625 -0.75), whereas when it was combined with reuterin or pediocin PA-1, it showed additive effects (FIC index = 1) against L. ivanovii HPB28. The inhibitory activity of synergetic consortia were tested against a large panel of Gram-positive and Gram-negative bacteria. According to our results, combining different antimicrobials with different mechanisms of action led to higher potency and a broad spectrum of inhibition, including multidrug-resistance pathogens.

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In vitro assessment of skin sensitization, irritability and toxicity of bacteriocins and reuterin for possible topical applications

2022-03-17, Biron, Éric, Frédéric Couture, Soltani, Samira, Fliss, Ismaïl, Subirade, Muriel, Boutin, Yvan.

Bacteriocins and reuterin are promising antimicrobials for application in food, veterinary, and medical sectors. In the light of their high potential for application in hand sanitizer, we investigated the skin toxicity of reuterin, microcin J25, pediocin PA-1, bactofencin A, and nisin Z in vitro using neutral red and LDH release assays on NHEK cells. We determined their skin sensitization potential using the human cell line activation test (h-CLAT). Their skin irritation potential was measured on human epidermal model EpiDerm™. We showed that the viability and membrane integrity of NHEK cells remained unaltered after exposure to bacteriocins and reuterin at concentrations up to 400 µg/mL and 80 mg/mL, respectively. Furthermore, microcin J25 and reuterin showed no skin sensitization at concentrations up to 100 µg/mL and 40 mg/mL, respectively, while pediocin PA-1, bactofencin A, and nisin Z caused sensitization at concentrations higher than 100 µg/mL. Tissue viability was unafected in presence of bacteriocins and reuterin at concentrations up to 200 µg/mL and 40 mg/ mL, respectively, which was confrmed by measuring cytokine IL-1α and IL-8 levels and by histological analysis. In conclusion, the current study provides scientifc evidence that some bacteriocins and reuterin, could be safely applied topically as sanitizers at recommended concentrations

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In vitro investigation of gastrointestinal stability and toxicity of 3-hyrdoxypropionaldehyde (reuterin) produced by Lactobacillus reuteri

2021-03-31, Soltani, Samira, Couture, Frédéric, Boutin, Yvan., Ben Said, Laila, Cashman-Kadri, Samuel, Subirade, Muriel, Biron, Éric, Fliss, Ismaïl

Reuterin (3-hyrdoxypropionaldehyde (3-HPA)) is a highly potent metabolite of L. reuteri, which has applications in food, health, and veterinary sectors. Similar to other natural antimicrobial compounds, the approval of reuterin as a bio-preservative or therapeutic agent by regulatory agencies relies on sufficient data on its cytotoxicity and behavior in the gastrointestinal environment. Although the antimicrobial activity of reuterin has been broadly studied, its safety and toxicity are yet to be explored in detail. In this study, the stability and activity of reuterin were investigated in the gastrointestinal tract using in vitro models simulating gastrointestinal conditions. In addition, hemolytic activity and in vitro cytotoxicity of reuterin were evaluated by neutral red assay and lactate dehydrogenase (LDH) colorimetric assay using the same cell line. Activity of reuterin was observed to be stable during gastrointestinal transit. Viability and membrane integrity of cells remained unaltered by reuterin up to 1080 mM concentration. Furthermore, no hemolysis was observed in blood cells exposed to 270 mM reuterin. This study provides unique and highly relevant in vitro data regarding gastrointestinal behavior and toxicity of reuterin. In conclusion, the current study indicates that within a certain concentration range, reuterin can be safely used in bio-preservation and therapeutics applications. However, further in vivo studies are required to confirm these findings.

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Gastrointestinal stability and cytotoxicity of bacteriocins from gram-positive and gram-negative bacteria : a comparative in vitro study

2022-01-25, Biron, Éric, Zirah, Séverine, Rebuffat, Sylvie, Soltani, Samira, Couture, Frédéric, Fliss, Ismaïl, Subirade, Muriel, Boutin, Yvan.

Bacteriocins are receiving increased attention as potent candidates in food preservation and medicine. Although the inhibitory activity of bacteriocins has been studied widely, little is known about their gastrointestinal stability and toxicity toward normal human cell lines. The aim of this study was to evaluate the gastrointestinal stability and activity of microcin J25, pediocin PA-1, bactofencin A and nisin using in vitro models. In addition cytotoxicity and hemolytic activity of these bacteriocins were investigated on human epithelial colorectal adenocarcinoma cells (Caco-2) and rat erythrocytes, respectively. Pediocin PA-1, bactofencin A, and nisin were observed to lose their stability while passing through the gastrointestinal tract, while microcin J25 is only partially degraded. Besides, selected bacteriocins were not toxic to Caco-2 cells, and integrity of cell membrane was observed to remain unaffected in presence of these bacteriocins at concentrations up to 400 μg/mL. In hemolysis study, pediocin PA-1, bactofencin A, and nisin were observed to lyse rat erythrocytes at concentrations higher than 50 μg/mL, while microcin J25 showed no effect on these cells. According to data indicating gastrointestinal degradation and the absence of toxicity of pediocin PA-1, bactofencin A, and microcin J25 they could potentially be used in food or clinical applications.