Rita D Shelby1, Natalie Tengberg1, Miriam Conces2, Jacob K Olson1, Jason B Navarro3, Michael T Bailey3, Steven D Goodman3, Gail E Besner1. 1. a Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Department of Pediatric Surgery , Nationwide Children's Hospital , Columbus , OH , USA. 2. b Department of Pathology , Nationwide Children's Hospital , Columbus , OH , USA. 3. c Center for Microbial Pathogenesis , The Research Institute at Nationwide Children's Hospital , Columbus , OH , USA.
Abstract
BACKGROUND: Clostridium difficile infection is the most common cause of antimicrobial-associated diarrhea. Our aim was to introduce a novel and efficient clinical sickness score (CSS), and to define a detailed histologic injury score (HIS) in a murine model of C. difficile colitis. METHODS: Mice received an antibiotic cocktail (kanamycin, gentamicin, colistin, metronidazole, and vancomycin) for 96 h. After 48 h, mice received an intraperitoneal injection of clindamycin, followed by oral C. difficile (1.5 × 107 CFU). Signs of sickness were scored using a novel CSS (range 0-12) with scores ≥6 consistent with C. difficile colitis. Intestinal tissue was analyzed utilizing an adapted HIS (range 0-9) with scores ≥4 consistent with C. difficile colitis. Stool was analyzed for C. difficile, and survival evaluated. RESULTS: No control mice showed signs of sickness, whereas 23% of mice receiving antibiotics alone and 65% of mice exposed to antibiotics and subsequently C. difficile demonstrated signs of sickness (p = 0.0134). No control mice had histologic injury, whereas 8% of mice receiving antibiotics alone and 75% of mice exposed to antibiotics followed by C. difficile had evidence of histologic injury (p = 0.0001). Mice exposed to C. difficile lost more weight, although not significant (p = 0.070). Mice that received C. difficile had decreased survival compared to control mice and mice receiving antibiotics only (p = 0.03). CONCLUSIONS: We have developed a novel clinical scoring system, and detailed histological grading system, that enables the objective evaluation of a murine C. difficile colitis model. This model allows the study of this disease in a host that demonstrates clinical and histologic signs comparable to human C. difficile infection. This will allow for improved study of therapeutics for this disease in the future.
BACKGROUND:Clostridium difficileinfection is the most common cause of antimicrobial-associated diarrhea. Our aim was to introduce a novel and efficient clinical sickness score (CSS), and to define a detailed histologic injury score (HIS) in a murine model of C. difficilecolitis. METHODS:Mice received an antibiotic cocktail (kanamycin, gentamicin, colistin, metronidazole, and vancomycin) for 96 h. After 48 h, mice received an intraperitoneal injection of clindamycin, followed by oral C. difficile (1.5 × 107 CFU). Signs of sickness were scored using a novel CSS (range 0-12) with scores ≥6 consistent with C. difficilecolitis. Intestinal tissue was analyzed utilizing an adapted HIS (range 0-9) with scores ≥4 consistent with C. difficilecolitis. Stool was analyzed for C. difficile, and survival evaluated. RESULTS: No control mice showed signs of sickness, whereas 23% of mice receiving antibiotics alone and 65% of mice exposed to antibiotics and subsequently C. difficile demonstrated signs of sickness (p = 0.0134). No control mice had histologic injury, whereas 8% of mice receiving antibiotics alone and 75% of mice exposed to antibiotics followed by C. difficile had evidence of histologic injury (p = 0.0001). Mice exposed to C. difficile lost more weight, although not significant (p = 0.070). Mice that received C. difficile had decreased survival compared to control mice and mice receiving antibiotics only (p = 0.03). CONCLUSIONS: We have developed a novel clinical scoring system, and detailed histological grading system, that enables the objective evaluation of a murineC. difficilecolitis model. This model allows the study of this disease in a host that demonstrates clinical and histologic signs comparable to humanC. difficileinfection. This will allow for improved study of therapeutics for this disease in the future.
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Authors: Felix Broecker; Erik Wegner; Bruna M S Seco; Paulina Kaplonek; Maria Bräutigam; Armin Ensser; Frederick Pfister; Christoph Daniel; Christopher E Martin; Jochen Mattner; Peter H Seeberger Journal: ACS Chem Biol Date: 2019-11-19 Impact factor: 5.100
Authors: Rita D Shelby; Grace E Janzow; Lauren Mashburn-Warren; Jeffrey Galley; Natalie Tengberg; Jason Navarro; Miriam Conces; Michael T Bailey; Steven D Goodman; Gail E Besner Journal: Gut Microbes Date: 2020-11-09