Revealing the lethal effects of Pasteurella multocida toxin on multiple organ systems
Jianlin Yuan1, Jinfeng Li1, Senyan Du1,2,3
1Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.
Abstract:
Pasteurella multocida toxin (PMT) is one of the most important virulence factors of Pasteurella multocida type D. Pasteurella multocida infection has caused enormous economic losses in the pig farming industry. Although it is well known that this bacterial infection causes progressive atrophic rhinitis, its effects on other organ tissues in pigs are unclear. In this study, PMT was expressed and purified, and the cytotoxic effects of PMT on four types of swine cells, LLC-PK1, PAM, IPEC, and ST, were investigated. LLC-PK1 exhibited the highest sensitivity to the cytotoxic effects of PMT. Our studies revealed that a PMT concentration of 0.1 μg/kg can lead to weight loss, whereas a PMT concentration of 0.5 μg/kg can lead to death in mice. PMT causes damage to the intestines, kidneys, lungs, livers, and spleens of mice. Furthermore, PMT caused acute death in pigs at treatment concentrations greater than 5 μg/kg; at PMT concentration of 2.5 μg/kg, weight loss occurred until death. PMT mainly caused damage to the hearts, lungs, livers, spleens and kidneys of pigs. The organ coefficient showed that damage to the heart and kidneys was the most severe and caused the renal pelvis and renal pyramid to dissolve and become cavitated. Pathology revealed hemorrhage in the lungs, liver, and spleen, and the kidneys were swollen and vacuolated, which was consistent with the damaged target organs in the mice. In conclusion, these findings demonstrate that PMT is extremely toxic in vitro and in vivo, causing damage to various organs of the body, especially the kidneys and lungs. This study provides a theoretical basis for the in-depth exploration of the cytotoxic effects of PMT on target organs.
Insights
Pasteurella multocida toxin (PMT) severely damages multiple organs in pigs and mice, particularly the kidneys and lungs. This study details PMT
Area of Science:
- Veterinary Pathology
- Microbial Toxinology
- Animal Science
Background:
- Pasteurella multocida type D causes significant economic losses in swine farming.
- While known for atrophic rhinitis, PMT's effects on other swine organs are not fully understood.
- PMT is a key virulence factor in Pasteurella multocida type D infections.
Purpose of the Study:
- To investigate the cytotoxic effects of Pasteurella multocida toxin (PMT) on swine cells.
- To determine the in vivo toxicity and target organs of PMT in mice and pigs.
- To elucidate the pathological damage caused by PMT in various organs.
Main Methods:
- Purification and expression of PMT.
- In vitro cytotoxicity assays on four swine cell lines (LLC-PK1, PAM, IPEC, ST).
- In vivo toxicity studies in mice and pigs, including dose-response and pathological examination.
Main Results:
- LLC-PK1 cells showed the highest sensitivity to PMT in vitro.
- PMT induced weight loss and death in mice at concentrations of 0.1 μg/kg and 0.5 μg/kg, respectively.
- PMT caused significant damage to the heart, kidneys, lungs, liver, and spleen in pigs, with severe renal and cardiac pathology.
Conclusions:
- PMT exhibits high in vitro and in vivo toxicity, affecting multiple organ systems.
- The kidneys and lungs are particularly susceptible to PMT-induced damage.
- Findings provide a foundation for further research into PMT's cytotoxic mechanisms and effects on target organs.
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