دورية أكاديمية
Temporins, small antimicrobial peptides with leishmanicidal activity
العنوان: | Temporins, small antimicrobial peptides with leishmanicidal activity |
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المؤلفون: | Mangoni, Maria Luisa, Saugar, José María, Dellisanti, Maria, Barra, Donatella, Simmaco, Maurizio, Rivas, Luis |
المساهمون: | Ministero dell'Istruzione, dell'Università e della Ricerca, Ministerio de Ciencia y Tecnología (España), Comunidad de Madrid, Red Española de Investigación en Patología Infecciosa |
بيانات النشر: | American Society for Biochemistry and Molecular Biology |
سنة النشر: | 2005 |
المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
الوصف: | 7 p.-6 fig.-1 tab. ; Leishmaniasis encompasses a wide range of infections caused by the human parasitic protozoan species belonging to the Leishmania genus. It appears frequently as an opportunistic disease, especially in virus-infected immunodepressed people. Similarly to other pathogens, parasites became resistant to most of the first-line drugs. Therefore, there is an urgent need to develop antiparasitic agents with new modes of action. Gene-encoded antimicrobial peptides are promising candidates, but so far only a few of them have shown anti-protozoa activities. Here we found that temporins A and B, 13-amino acid antimicrobial peptides secreted from the skin of the European red frog Rana temporaria, display anti-Leishmania activity at micromolar concentrations, with no cytolytic activity against human erythrocytes. To the best of our knowledge, temporins represent the shortest natural peptides having the highest leishmanicidal activity and the lowest number of positively charged amino acids (a single lysine/arginine) and maintain biological function in serum. Their lethal mechanism involves plasma membrane permeation based on the following data. (i) They induce a rapid collapse of the plasma membrane potential. (ii) They induce the influx of the vital dye SYTOX Green. (iii) They reduce intracellular ATP levels. (iv) They severely damage the membrane of the parasite, as shown by transmission electron microscopy. Besides giving us basic important information, the unique properties of temporins, as well as their membranolytic effect, which should make it difficult for the pathogen to develop resistance, suggest them as potential candidates for the future design of antiparasitic drugs with a new mode of action. ; This work was supported by grants from the Italian Ministero dell’Istruzione, dell’Universita` e della Ricerca, Universita` La Sapienza, and the Spanish Ministry of Science and Technology Grant BIO2003-09056-CO2-2, the Comunidad Autonoma de Madrid Grant 08.2/0054/2001.02, Plan Estratégico de Grupos en ... |
نوع الوثيقة: | article in journal/newspaper |
اللغة: | English |
تدمد: | 0021-9258 1083-351X |
العلاقة: | Publisher's version; http://dx.doi.org/10.1074/jbc.M410795200Test; Sí; J Biol Chem 280(2):984-90 (2005); http://hdl.handle.net/10261/162427Test; http://dx.doi.org/10.13039/501100003407Test; http://dx.doi.org/10.13039/501100006280Test; http://dx.doi.org/10.13039/100012818Test |
DOI: | 10.1074/jbc.M410795200 |
DOI: | 10.13039/501100003407 |
DOI: | 10.13039/501100006280 |
DOI: | 10.13039/100012818 |
الإتاحة: | https://doi.org/10.1074/jbc.M410795200Test https://doi.org/10.13039/501100003407Test https://doi.org/10.13039/501100006280Test https://doi.org/10.13039/100012818Test http://hdl.handle.net/10261/162427Test |
حقوق: | open |
رقم الانضمام: | edsbas.96360DAD |
قاعدة البيانات: | BASE |
تدمد: | 00219258 1083351X |
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DOI: | 10.1074/jbc.M410795200 |