Lactococcus lactis ssp. lactis biovar. diacetylactis UL719 et la nisine : une nouvelle approche dans le traitement des infections à Clostridium difficile

Authors: Le Lay, Christophe
Advisor: Fliss, IsmaïlOuellette, Marc
Abstract: Clostridium difficile is the most frequently identified enteric pathogen in patients with nosocomial antibiotic-associated diarrhea and pseudomembranous colitis. The most common drugs used to treat diseases associated with C. difficile are limited to metronidazole and vancomycin since most clinically isolated C. difficile strains are resistant to many antibiotics currently used to treat Gram-positive bacterial infections. The search for new treatments to limit the impact of C. difficile becomes an urgent need for the health sector. The use of probiotics, particularly metabolically active lactic acid bacteria, was recently proposed as an alternative for the medical community. In this context, the aim of the study was to investigate the capacity of the lactic acid bacteria Lactococcus lactis UL719 and nisin to inhibit C. difficile in intestinal conditions. First, the antibacterial activity of nisin against clinical strains of C. difficile showed that it was active with minimum inhibitory concentrations between 0.8 and 51.2 µg/mL, depending on the strains. In addition, nisin was able to inhibit spore germination of C. difficile. Given these results, the survival of the nisin-producing strain, L. lactis UL719 and the physicochemical stability of nisin were evaluated using a simulator of the gastrointestinal tract. The results demonstrated the ability of the nisin producing strain to survive the gastrointestinal tract with a 0.5 % survival rate and, despite the conditions of gastrointestinal stress, to keep its ability to produce the bacteriocin. However, the nisin alone lost its antimicrobial activity after its passage through the duodenum. Finally, when the antimicrobial activity was evaluated in an in vitro model of colic fermentation simulating physiological intestinal conditions, L. lactis UL719 had no effect on C. difficile, but nisin showed a complete inhibition of this pathogen. It was also observed that nisin had a slight inhibitory effect on the Gram-positive bacterial population in the in vitro human colic model, but the effect was temporary.
Document Type: Thèse de doctorat
Issue Date: 2015
Open Access Date: 23 April 2018
Grantor: Université Laval
Collection:Thèses et mémoires

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