Abstract
Leishmaniasis is a neglected tropical disease with 1.6 million new cases reported each year. However, there are few safe, effective, and affordable treatments provided to those affected by this disease. Still under-appreciated as potential pharmaceutical targets, especially for cutaneous leishmaniasis infections, are the two isozymes of secreted acid phosphatase (SAP). These enzymes are involved in the survival of the parasite in the sand fly vector, and in infecting host macrophages. While the application of electric or electromagnetic fields as a medicinal therapeutic is not new, the utility of electric field application for the treatment of leishmaniasis is under studied. Studies involving the effects of electric fields on the cell secretion of SAP or the activity of SAP that has been secreted prior to electrical stimulation have not yet been reported. This work is the first report on the effect of specific electric fields on the activity of Leishmania tarentolae secreted acid phosphatases and the modulation of this secretion from the cells. In addition, the kinetic constants for the enzyme isoforms were determined as a function of days in culture and removal of carbohydrate from the glycosylated enzymes, while using a glycosidase, was shown to affect these kinetic constants.
Highlights
Results from this work suggest that Leishmania secreted acid phosphatases, which were reported to be important in all species of Leishmania [12,25,26], remain as potential therapeutic targets for the treatment of leishmaniasis, and that treatment with electric fields may present a critical enhancement to available treatment options
From our studies, which demonstrated the modulation in the enzyme activity while using electrical stimulation, either by directly affecting enzyme activity or by modulation of the release of the cell associated secreted acid phosphatase prematurely or too slowly, we speculate that this could affect the critical parasite-host interactions needed for successful infections
We suggest that parasite migration to a focal area by the application of electrical fields could increase the effectiveness of topical therapeutics, and might be a useful combined therapy for the treatment of cutaneous leishmaniasis
Summary
Leishmaniasis presents clinically in three forms: cutaneous, visceral, and mucocutaneous, with cutaneous being the most prevalent form. Over 1.6 million new cases of leishmaniasis diseases are reported yearly [2]. Current therapeutic options include treatment with either pentavalent antimony salts, amphotericin B, liposomal amphotericin B, miltefosine, pentamidine, paromomycin, ketoconazole, itraconazole, or fluconazole [3,4]. Individual treatment costs range from $20 to $252 USD per day and they must be administered for 20 to 120 days or longer, depending on healing process duration [5]. While Leishmania diseases are becoming more prevalent, there are few cost-efficient and effective drug therapies. Electric field stimulation, a non-drug treatment, should be included in the search for new and effective treatments against leishmaniasis
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