Skip to main content Accessibility help

Effect of aliphatic, monocarboxylic, dicarboxylic, heterocyclic and sulphur-containing amino acids on Leishmania spp. chemotaxis

  • E. DIAZ (a1), A. K. ZACARIAS (a1), S. PÉREZ (a1), O. VANEGAS (a1), L. KÖHIDAI (a2), M. PADRÓN-NIEVES (a1) and A. PONTE-SUCRE (a1)...


In the sand-fly mid gut, Leishmania promastigotes are exposed to acute changes in nutrients, e.g. amino acids (AAs). These metabolites are the main energy sources for the parasite, crucial for its differentiation and motility. We analysed the migratory behaviour and morphological changes produced by aliphatic, monocarboxylic, dicarboxylic, heterocyclic and sulphur-containing AAs in Leishmania amazonensis and Leishmania braziliensis and demonstrated that L-methionine (10−12 m), L-tryptophan (10−11 m), L-glutamine and L-glutamic acid (10−6 m), induced positive chemotactic responses, while L-alanine (10−7 m), L-methionine (10−11 and 10−7 m), L-tryptophan (10−11 m), L-glutamine (10−12 m) and L-glutamic acid (10−9 m) induced negative chemotactic responses. L-proline and L-cysteine did not change the migratory potential of Leishmania. The flagellum length of L. braziliensis, but not of L. amazonensis, decreased when incubated in hyperosmotic conditions. However, chemo-repellent concentrations of L-alanine (Hypo-/hyper-osmotic conditions) and L-glutamic acid (hypo-osmotic conditions) decreased L. braziliensis flagellum length and L-methionine (10−11 m, hypo-/hyper-osmotic conditions) decreased L. amazonensis flagellum length. This chemotactic responsiveness suggests that Leishmania discriminate between slight concentration differences of small and structurally closely related molecules and indicates that besides their metabolic effects, AAs play key roles linked to sensory mechanisms that might determine the parasite's behaviour.


Corresponding author

* Corresponding author. Laboratory of Molecular Physiology, Institute of Experimental Medicine, Faculty of Medicine, Universidad Central de Venezuela, Caracas, Venezuela. E-mail:


Hide All
Atías, A. (1998). Parasitología Médica: Leishmaniasis, 2nd Edn. Publicaciones Técnicas Mediterráneo, Santiago de Chile.
Barros, V., Gontijo, N., Melo, M. and Oliveira, J. (2006). Leishmania amazonensis: chemotaxic and osmotaxic responses in promastigotes and their probable role in development in the phlebotomine gut. Experimental Parasitology 112, 152157.
Bates, P. (2008). Leishmania sand fly interaction: progress and challenges. Current Opinion Microbiology 11, 340344.
Bengs, F., Scholz, A., Kuhn, D. and Wiese, M. (2005). LmxMPK9, a mitogen-activated protein kinase homologue affects flagellar length in Leishmania mexicana . Molecular Microbiology 55, 16061615.
Blaineau, C., Tessier, M., Dubessay, P., Tasse, L., Crobu, L., Page's, M. and Bastien, P. (2007). A novel microtubule-depolymerizing Kinesin involved in length control of a Eukaryotic Flagellum. Current Biology 17, 778782.
Botero, D. and Restrepo, M. (2003). Parasitosis humanas, 4th Edn. Corporación para Investigaciones Biológicas, Bogotá, Colombia.
Burrows, C. and Blum, J. (1991). Effect of hyper-osmotic stress on alanine content of Leishmania major promastigotes. Journal of Protozoology 38, 4752.
Darling, T. and Blum, J. (1990). Changes in the shape of Leishmania major promastigotes in response to hexoses, proline, and hypo-osmotic stress. Journal of Protozoology 37, 267272.
Diaz, E., Köhidai, L., Ponte-Sucre, A., Ríos, A. and Vanegas, O. (2011). Ensayos de quimiotaxis in vitro en Leishmania spp. Evaluación de la técnica de los capilares-dos cámaras en promastigotes. Revista de la Facultad de Farmacia-UCV 74, 3139.
Diaz, E., Köhidai, L., Ríos, A., Vanegas, O., Silva, A., Szabó, R., Mezo, G., Hudecz, F. and Ponte-Sucre, A. (2013) Leishmania braziliensis: cytotoxic, cytostatic and chemotactic effects of poly-lysine-Methotrexate-conjugates. Experimental Parasitology 135, 134141.
Dillon, R. J., Ivens, A. C., Churcher, C., Holroyd, N., Quail, M. A., Rogers, M. E., Soares, M. B., Bonaldo, M. F., Casavant, T. L., Lehane, M. J. and Bates, P. A. (2006). Analysis of ESTs from Lutzomyia longipalpis sand flies and their contribution toward understanding the insect-parasite relationship. Genomics 88, 831840.
Dostálová, A. and Volf, P. (2012). Leishmania development in sand flies: parasite vector interactions overview. Parasites and Vectors 5, 276.
Erdmann, M., Scholz, A., Melzer, I., Schmetz, C. and Wiese, M.(2006). Interacting protein kinases involved in the regulation of Flagellar length. Molecular Biology of the Cell 17, 20352045.
Forestier, C., Machu, M., Loussert, C., Pascale, P. and Spath, F. (2011). Imaging host cell-Leishmania interaction dynamics implicates parasite motility, lysosome recruitment, and host cell wounding in the infection process. Cell Host and Microbe 9, 319330.
Gadelha, C., Wickstead, B. and Gull, K. (2007). Flagellar and ciliary beating in trypanosomome motility. Cell Motility and the Cytoskeleton 64, 629643.
Handman, E., Goding, J., Papenfuss, A. and Speed, T. (2008). Leishmania surface proteins. In Leishmania, after the Genome (ed. Fasel, N. and Myler, P.), pp. 177204. Caister Academic Press, England.
Hart, D. T. and Coombs, G. H. (1982). Leishmania mexicana: energy metabolism of amastigotes and promastigotes. Experimental Parasitology 54, 397409.
Inbar, E., Schlisselber, D., Suter Grotemeyer, M., Rentsch, D. and Zilberstein, D. (2013). A versatile proline/alanine transporter in the unicellular pathogen Leishmania donovani regulates amino acid homoeostasis and osmotic stress responses. Biochemical Journal 449, 555566.
Jagušić, M., Forčić, D., Brgles, M., Kutle, L., Šantak, M., Jergović, M., Kotarski, L., Bendelja, K. and Halassy, B. (2015). Stability of minimum essential medium functionality despite L-glutamine decomposition. Cytotechnology [Epub ahead of print] doi:10.1007/s10616-015-9875-8.
Köhidai, L. and Csaba, G. (2003). Chemotactic range fitting of amino acids and its correlations to physicochemical parameters in Tetrahymena pyriformis evolutionary consequences. Cellular and Molecular Biology 49, 487495.
Köhidai, L., Csaba, G. and Lemberkovics, E. (1995). Molecule dependent chemotactic responses of Tetrahymena pyriformis elicited by volatile oils. Acta Protozoologica 34, 181185.
Köhidai, L., Bösze, S., Hudecz, F., Illyés, E., Lang, O., Mák, M., Sebestyen, F. and Sóos, P. (2003). Chemotactic activity of oligopeptides containing and EWS motif on Tetrahymena pyriformis: the effect of amidation of the C-terminal residue. Cell Biochemistry Function 21, 113120.
LeFurgey, A., Blum, J. and Ingram, P. (2000). Compartmental responses to acute osmotic stress in Leishmania major result in rapid loss of Na+ and Cl . Comparative Biochemistry and Physiology. Part A: Molecular & Integrative Physiology 128, 385393.
Leslie, G., Barret, M. and Burchmore, R. (2002). Leishmania mexicana: promastigotes migrate through osmotic gradients. Experimental Parasitology 102, 117120.
Motulsky, H. (1995). Intuitive Biostatistics. Oxford University Press, New York, USA.
Opperdoes, F. and Michels, P. (2008). The metabolic repertoire of Leishmania and implication for drug discovery. In Leishmania, after the Genome (ed. Fasel, N. and Myler, P.), pp. 123158. Caister Academic Press, England.
Paes, L., Daliry, A., Floeter-Winter, L., Galvez, R. and Ramírez, M. (2008). Active transport of Glutamate in Leishmania amazonensis . Journal of Eukaryotic Microbiology 55, 382387.
Pajouhesh, H. and Lenz, G. (2005) Medicinal chemical properties of successful central nervous system drugs. Neurotherapeutics 2, 541553.
Peters, E., Ansel, J., Ericson, M., Hordinsky, M., Hosoi, J., Paus, R., Scholzen, T. and Seiffert, K. (2006). Neuropeptide control mechanisms in cutaneous biology; physiological and clinical significance. Journal of Investigative Dermatology 126, 19371947.
Pozzo, L. Y., Fontes, A., de Thomaz, A. A., Santos, B. S., Farias, P. M., Ayres, D. C., Giorgio, S. and Cesar, C. L. (2009) Studying taxis in real time using optical tweezers: applications for Leishmania amazonensis parasites. Micron 40, 617620.
Rotureau, B., Bastin, P., Morales, M. and Spath, G. (2009). The flagellum mitogen activated protein kinase connection in Trypanosomatids: a key sensory role in parasite signaling and development. Cell Microbiology 11, 710718.
Santos, V. C., Araujo, R. N., Machado, L. A., Pereira, M. H. and Gontijo, N. F. (2008). The physiology of the midgut of Lutzomyia longipalpis (Lutz and Neiva 1912): pH in different physiological conditions and mechanisms involved in its control. Journal of Experimental Biology 211 (Pt 17), 27922798.
Santos, V. C., Nunes, C. A., Pereira, M. H. and Gontijo, N. F. (2011). Mechanisms of pH control in the midgut of Lutzomyia longipalpis: roles for ingested molecules and hormones. Journal of Experimental Biology 214 (Pt 9), 14111418.
Santos, V. C., Vale, V. F., Silva, S. M., Nascimento, A. A., Saab, N. A., Soares, R. P., Michalick, M. S., Araujo, R. N., Pereira, M. H., Fujiwara, R. T. and Gontijo, N. F. (2014). Host modulation by a parasite: how Leishmania infantum modifies the intestinal environment of Lutzomyia longipalpis to favor its development. PLoS ONE 9, e111241. eCollection 2014.
Szemes, Á., Lajkó, E., Láng, O. and Kőhidai, L. (2015). Chemotactic effect of mono and disaccharides on the unicellular Tetrahymena pyriformis . Carbohydrate Research 407, 158165.
Vieira, L., Lafuente, E., Gamarro, F. and Cabantchik, Z. (1996). An amino acid channel activated by hypotonically induced swelling of Leishmania major promastigotes. The Biochemical Journal 319, 691697.
Voet, D., Voet, J. and Pratt, C. (2007). Fundamentos de Bioquímica, Aminoácidos, 2nd edición. Editorial Médica Panamericana, Argentina.



Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed