Hostname: page-component-78c5997874-fbnjt Total loading time: 0 Render date: 2024-11-19T13:22:11.707Z Has data issue: false hasContentIssue false
  • English
  • Français

Cell differentiation and infectivity of Leishmania mexicana are inhibited in a strain resistant to an ABC-transporter blocker

Published online by Cambridge University Press:  13 May 2004

N. SILVA ,
N. CAMACHO ,
K. FIGARELLA  and
A. PONTE-SUCRE
N. SILVA
Affiliation:
Laboratory of Molecular Physiology, Instituto de Medicina Experimental, Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela
N. CAMACHO
Affiliation:
Laboratory of Molecular Physiology, Instituto de Medicina Experimental, Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela
K. FIGARELLA
Affiliation:
Laboratory of Molecular Physiology, Instituto de Medicina Experimental, Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela
A. PONTE-SUCRE
Affiliation:
Laboratory of Molecular Physiology, Instituto de Medicina Experimental, Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela Present address, Institute for Molecular Biology of Infectious Diseases, University of Würzburg, Röntgenring 11, D-97070 Würzburg, Germany. Tel: +49 931 31 2627. Fax: +49 931 31 2578. E-mail: aiponte@reacciun.ve
Get access Rights & Permissions [Opens in a new window]

Abstract

We analysed whether markers of cell differentiation and infectivity differed when compared to the parental sensitive strain [NR(Gs)] in an in vitro selected Leishmania strain [NR(Gr)] resistant to Glibenclamide®, an ATP-binding-cassette (ABC)-transporter blocker. The data show that the cell body area was larger in NR(Gr) compared to NR(Gs) and that functional characters associated with an infective metacyclic phenotype, such as resistance to the lytic effect of the alternative complement pathway and expression of the Meta-1 protein, were reduced. The infectivity of NR(Gr) to J774.1 macrophages was also significantly reduced. These results suggest that resistance in Leishmania against Glibenclamide®, a general blocker of P-glycoproteins, could produce functional modifications that may be relevant for Leishmania differentiation, infectivity and survival.

Keywords

cell differentiationcell survivaldrug resistanceinfectivityLeishmania mexicana
Type
Research Article
Information
Parasitology , Volume 128 , Issue 6 , June 2004 , pp. 629 - 634
Copyright
2004 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

BASSELIN, M. & ROBERT-GERO, M. ( 1998). Alterations in membrane fluidity, lipid metabolism, mitochondrial activity and lipophosphoglycan expression in pentamidine-resistant Leishmania. Parasitology Research 60, 78–83.Google Scholar
BATES, P. A. & TETLEY, L. ( 1993). Leishmania mexicana: induction of metacyclogenesis by cultivation of promastigotes at acidic pH. Experimental Parasitology 76, 412–423.CrossRefGoogle Scholar
BERBERICH, C., MARÍN, M., RAMÍREZ, J. R., MUSKUS, C. & VÉLEZ, I. D. ( 1998). The metacyclic stage-expressed Meta-1 gene is conserved between Old and New World Leishmania species. Memórias Instituto Oswaldo Cruz 93, 819–821.CrossRefGoogle Scholar
ERESH, S., MENDOZA-LEÓN, A. & BARKER, D. C. ( 1993). A small chromosome of Leishmania (Viannia) lainsoni occupies a unique niche within the subgenus Viannia. Transactions of the Royal Society of Tropical Medicine and Hygiene 89, 231–236.Google Scholar
GARCÍA, N., FIGARELLA, K., MENDOZA-LEÓN, A. & PONTE-SUCRE, A. ( 2000). Changes in the infectivity, pyruvate kinase and acid phosphatase activity and P-glycoprotein expression in glibenclamide resistant Leishmania mexicana. Parasitology Research 86, 899–904.CrossRefGoogle Scholar
GOLSTEIN, P. E., BOOM, A., VAN GEFFEL, J., JACOBS, P., MASERET, B. & BEAUWENS, R. ( 1999). P-glycoprotein inhibition by glibenclamide and related compounds. Pflüger's Archiv 437, 652–660.CrossRefGoogle Scholar
INAGAKI, N., GONOI, T., CLEMENT IV, J. P., NAMBA, N., INAZAWA, J., GONZALEZ, G., AGUILAR-BRYAN, L., SEINO, S. & BRYAN, J. ( 1995). Reconstitution of IKATP: an inward rectifier sub-unit plus the sulfonylurea receptor. Science 270, 1166–1169.CrossRefGoogle Scholar
ISMACH, R., CIANCI, C. M. L., CAULFIELD, J. P., LANGER, P. J., HEIN, A. & McMAHON-PRATT, D. ( 1989). Flagellar membrane and paraxial rod proteins of Leishmania: characterization employing monoclonal antibodies. Journal of Protozoology 36, 617–624.CrossRefGoogle Scholar
LÉGARÉ, D., HETTEMA, E. & OUELLETTE, M. ( 1994). The P-glycoprotein-related gene family in Leishmania. Molecular and Biochemical Parasitology 68, 81–91.CrossRefGoogle Scholar
LOUAISSINI, M., ADROHER, F. J., FOULQIUIE, M. R. & BENITEZ, R. ( 1994). Investigations on the in vitro metacyclogenesis of a visceral and a cutaneous human strain of Leishmania infantum. Acta Tropica 70, 355–368.Google Scholar
LUIS, L., RAMÍREZ, A., AGUILAR, C. M., ERESH, S., BARKER, D. C. & MENDOZA-LEÓN, A. ( 1998). The genomic fingerprinting of the coding region of the beta-tubulin gene in Leishmania identification. Acta Tropica 69, 193–204.CrossRefGoogle Scholar
MBONGO, N., LOISEAU, P. M., BILLION, M. A. & ROBERT-GERO, M. ( 1998). Mechanism of amphotericin B resistance in Leishmania donovani promastigotes. Antimicrobial Agents and Chemotherapy 42, 352–357.Google Scholar
NOURBAKHSH, F., ULIANA, S. R. & SMITH, D. F. ( 1996). Characterisation and expression of a stage-regulated gene of Leishmania major. Molecular and Biochemical Parasitology 76, 201–213.CrossRefGoogle Scholar
PENIN, P., GAMALLO, C., PENIN, M. L., MAYER, F., DEL REY, J. & DE DIEGO, J. A. ( 1992). Analytic morphometry of the Trypanosoma cruzi (Bolivia strain) forms found in the intestine of Rhodnius prolixus. Memórias Instituto Oswaldo Cruz 63, 159–161.CrossRefGoogle Scholar
PONTE-SUCRE, A., CAMPOS, Y., VÁSQUEZ, J., MOLL, H. & MENDOZA-LEÓN, A. ( 1997). Sensitivity of Leishmania spp. to glibenclamide and 4-aminopiridine: a tool for the study of drug resistance development. Memórias Instituto Oswaldo Cruz 92, 601–606.Google Scholar
PONTE-SUCRE, A., CAMPOS, Y., FERNÁNDEZ, M., MOLL, H. & MENDOZA-LEÓN, A. ( 1998). Leishmania sp.: Growth and survival are impaired by ion channel blockers. Experimental Parasitology 88, 11–19.Google Scholar
ROGERS, M. E., CHANCE, M. L. & BATES, P. A. ( 2002). The role of promastigote secretory gel in the origin and transmission of the infective stage of Leishmania mexicana by the sandfly Lutzomyia longipalpis. Parasitology 124, 495–507.CrossRefGoogle Scholar
SACKS, D. L. & PERKINS, P. V. ( 1984). Development of infective stage Leishmania promastigotes within phlebotomine sand flies. American Journal of Tropical Medicine and Hygiene 34, 456–459.Google Scholar
SACKS, D. L. & DA SILVA, P. ( 1987). The generation of the infective stage Leishmania major promastigotes is associated with the cell surface expression and release of a developmentally regulated glycolipid. Immunology 139, 3099–3106.Google Scholar
SCHEFLER, W. ( 1981). Análisis de varianza. In Bioestadística ( ed. Schefler, W.), pp. 122–157. Fondo Educativo Interamericano, México.
SERENO, D., GUILVARD, E., MAQUAIRE, S., CAVALEYRA, M., HOLZMULLER, P., OUAISSI, A. & LEMESRE, J. L. ( 2001). Experimental studies on the evolution of antimony-resistant phenotype during the in vitro life cycle of Leishmania infantum: implications for the spread of chemoresistance in endemic areas. Acta Tropica 80, 195–205.CrossRefGoogle Scholar
SILVA, N. & PONTE-SUCRE, A. ( 2001). ABC proteins in Leishmania mexicana: Modulation of parasite host cell interaction. Archivos Venezolanos de Farmacología y Terapéutica 20, 134–138.Google Scholar
ULIANA, S. R. B., GOYAL, N., FREYMULLER, E. & SMITH, D. E. ( 1999). Overexpression and comparative structural analysis of the satage-regulated meta-1 gene. Experimental Parasitology 92, 183–191.CrossRefGoogle Scholar
ZAKAI, H. A., CHANCE, M. L. & BATES, P. A. ( 1997). In vitro stimulation of metacyclogenesis in Leishmania braziliensis, L. donovani, L. major and L. mexicana. Parasitology 116, 305–309.Google Scholar