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Recombinant murine toxin from Yersinia pestis shows high toxicity and β-adrenergic blocking activity in mice
Yanxiao Fan1, Yazhou Zhou2, Na Feng1
1Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, People's Republic of China; Laboratory of Analytical Microbiology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, No. 20, Dongdajie, Fengtai, Beijing 100071, People's Republic of China.
Abstract:
Yersinia pestis murine toxin (Ymt) encoded on pMT1 is a 61-kDa protein, a member of the phospholipase D superfamily, which is found in all the domains of life. It is considered to be an intracellular protein required for the survival of Y. pestis in the midgut of the flea, but the exact role of Ymt in the pathogenesis of Y. pestis has not been clarified. Purified Ymt is highly toxic to mice and rats, but the exact mechanism of the animals' death is unclear. Here, we prepared a recombinant Ymt in Escherichia coli BL21 cells, and determined its toxicity and activity. We demonstrated that recombinant Ymt was as toxic to mice as the native protein when administered via the intraperitoneal or intravenous route, and inhibited the elevation of blood sugar caused by adrenaline. We also demonstrated that recombinant Ymt was highly toxic to mice when administered via the muscular or subcutaneous route. We also show that the multiple organ congestion or hemorrhage caused by Ymt poisoning may explain the death of the mice.
Insights
Yersinia pestis murine toxin (Ymt) is highly toxic to mice, causing organ congestion and hemorrhage. This study clarifies Ymt
Area of Science:
- Microbiology
- Toxicology
- Molecular Biology
Background:
- Yersinia pestis murine toxin (Ymt), a phospholipase D superfamily member, is crucial for Y. pestis survival in fleas.
- The precise role of Ymt in Y. pestis pathogenesis and the mechanism of host toxicity remain unclear.
Purpose of the Study:
- To characterize the toxicity and activity of recombinant Ymt.
- To elucidate the mechanism behind Ymt-induced lethality in mammals.
Main Methods:
- Recombinant Ymt was expressed in Escherichia coli BL21 cells.
- Toxicity was assessed in mice via intraperitoneal, intravenous, intramuscular, and subcutaneous administration.
- Ymt's effect on adrenaline-induced hyperglycemia was evaluated.
Main Results:
- Recombinant Ymt exhibited toxicity comparable to native Ymt in mice via systemic routes.
- Ymt demonstrated high toxicity via intramuscular and subcutaneous routes.
- Ymt administration led to multiple organ congestion and hemorrhage in mice.
- Ymt inhibited adrenaline-induced elevation of blood sugar.
Conclusions:
- Recombinant Ymt effectively mimics native Ymt toxicity.
- Ymt-induced organ congestion and hemorrhage are likely mechanisms of Ymt poisoning.
- Ymt's role in Y. pestis pathogenesis warrants further investigation.
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