In vitro evidence for a bacterial pathogenesis of equine laminitis.
Abstract: Utilizing an in vitro laminitis explant model, we have investigated how bacterial broth cultures and purified bacterial proteases activate matrix metalloproteinases (MMPs) and alter structural integrity of cultured equine lamellar hoof explants. Four Gram-positive Streptococcus spp. and three Gram-negative bacteria all induced a dose-dependent activation of MMP-2 and MMP-9 and caused lamellar explants to separate. MMP activation was deemed to have occurred if a specific MMP inhibitor, batimastat, blocked MMP activity and prevented lamellar separation. Thermolysin and streptococcal pyrogenic exotoxin B (SpeB) both separated explants dose-dependently but only thermolysin was inhibitable by batimastat or induced MMP activation equivalent to that seen with bacterial broths. Additionally, thermolysin and broth MMP activation appeared to be cell dependent as MMP activation did not occur in isolation. These results suggest the rapid increase in streptococcal species in the caecum and colon observed in parallel with carbohydrate induced equine laminitis may directly cause laminitis via production of exotoxin(s) capable of activating resident MMPs within the lamellar structure. Once activated, these MMPs can degrade key components of the basement membrane (BM) hemidesmosome complex, ultimately separating the BM from the epidermal basal cells resulting in the characteristic laminitis histopathology of hoof lamellae. While many different causative agents have been evaluated in the past, the results of this study provide a unifying aetiological mechanism for the development of carbohydrate induced equine laminitis.
Publication Date: 2001-03-10 PubMed ID: 11240100DOI: 10.1016/s0378-1135(00)00359-xGoogle Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research article focuses on investigating the role of bacterial pathogens in the development of equine laminitis, a painful hoof condition in horses. The study, through the use of an in vitro laminitis model, shows that various bacteria types can activate enzymes that damage the hoof structure, indicating a bacterial direct cause of the disease.
Study Methodology
- The researchers used an in vitro laminitis explant model to conduct their research. This involved a laboratory model mimicking the disease conditions.
- They examined the effects of bacterial broths and specific bacterial enzymes, known as proteases, on the activation of Matrix Metalloproteinases (MMPs), a group of enzymes that affect the structure and function of tissues.
- The bacteria strains involved were four types of Gram-positive Streptococcus species and three types of Gram-negative bacteria.
Findings
- Activation of MMP-2 and MMP-9 was found to be dose-dependent, meaning the more bacteria involved, the greater the activation of these enzymes.
- If batimastat, a specific MMP inhibitor, blocked MMP activity and prevented the separation of lamellar explants, this was taken as confirmation of MMP activation
- Exposure to thermolysin and streptococcal pyrogenic exotoxin B (SpeB) resulted in lamellar explant separation, but only thermolysin could be inhibited by batimastat.
- The activation of MMPs from thermolysin and the bacterial broth was found to be cell dependent, suggesting they don’t function independently.
Implications
- Findings suggest Streptococcal species, when rapidly increased in the horse’s digestive tract in relation to carbohydrate induction, may directly cause laminitis through the production of certain exotoxins that activate MMPs present in the lamellar structure.
- Once these MMPs are activated, they can degrade vital components of the basement membrane, separating it from the epidermal basal cells and resulting in traditional laminitis pathology.
- The study provides a possibility for a unified cause of carbohydrate-induced equine laminitis, which has often been attributed to numerous other agents in the past.
Cite This Article
APA
Mungall BA, Kyaw-Tanner M, Pollitt CC.
(2001).
In vitro evidence for a bacterial pathogenesis of equine laminitis.
Vet Microbiol, 79(3), 209-223.
https://doi.org/10.1016/s0378-1135(00)00359-x Publication
Researcher Affiliations
- Department of Companion Animal Sciences, School of Veterinary Science, The University of Queensland, St. Lucia, Qld 4072, Australia.
MeSH Terms
- Animals
- Bacterial Proteins
- Cysteine Endopeptidases / pharmacology
- Electrophoresis, Polyacrylamide Gel / veterinary
- Enzyme Activation
- Foot Diseases / enzymology
- Foot Diseases / microbiology
- Foot Diseases / pathology
- Foot Diseases / veterinary
- Gram-Negative Bacteria / pathogenicity
- Histocytochemistry / veterinary
- Hoof and Claw / enzymology
- Hoof and Claw / microbiology
- Hoof and Claw / pathology
- Horse Diseases / enzymology
- Horse Diseases / microbiology
- Horse Diseases / pathology
- Horses
- Lameness, Animal / enzymology
- Lameness, Animal / microbiology
- Lameness, Animal / pathology
- Matrix Metalloproteinase 2 / metabolism
- Matrix Metalloproteinase 9 / metabolism
- Phenylalanine / analogs & derivatives
- Phenylalanine / pharmacology
- Protease Inhibitors / pharmacology
- Streptococcus bovis / pathogenicity
- Thermolysin / pharmacology
- Thiophenes / pharmacology
Citations
This article has been cited 8 times.- Fischer NG, Aparicio C. Junctional epithelium and hemidesmosomes: Tape and rivets for solving the "percutaneous device dilemma" in dental and other permanent implants.. Bioact Mater 2022 Dec;18:178-198.
- Li H, Liu J, Zhu W, Mao S. Intraruminal infusion of oligofructose alters ruminal microbiota and induces acute laminitis in sheep.. J Anim Sci 2017 Dec;95(12):5407-5419.
- Reisinger N, Dohnal I, Nagl V, Schaumberger S, Schatzmayr G, Mayer E. Fumonisin B₁ (FB₁) Induces Lamellar Separation and Alters Sphingolipid Metabolism of In Vitro Cultured Hoof Explants.. Toxins (Basel) 2016 Mar 24;8(4):89.
- Reisinger N, Schaumberger S, Nagl V, Hessenberger S, Schatzmayr G. Concentration Dependent Influence of Lipopolysaccharides on Separation of Hoof Explants and Supernatant Lactic Acid Concentration in an Ex Vivo/In Vitro Laminitis Model.. PLoS One 2015;10(11):e0143754.
- Reisinger N, Schaumberger S, Nagl V, Hessenberger S, Schatzmayr G. Milk thistle extract and silymarin inhibit lipopolysaccharide induced lamellar separation of hoof explants in vitro.. Toxins (Basel) 2014 Oct 6;6(10):2962-74.
- Shepherd ML, Ponder MA, Burk AO, Milton SC, Swecker WS Jr. Fibre digestibility, abundance of faecal bacteria and plasma acetate concentrations in overweight adult mares.. J Nutr Sci 2014;3:e10.
- Endo A, Futagawa-Endo Y, Dicks LM. Lactobacillus and Bifidobacterium diversity in horse feces, revealed by PCR-DGGE.. Curr Microbiol 2009 Dec;59(6):651-5.
- Bailey SR, Baillon ML, Rycroft AN, Harris PA, Elliott J. Identification of equine cecal bacteria producing amines in an in vitro model of carbohydrate overload.. Appl Environ Microbiol 2003 Apr;69(4):2087-93.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists