Temperature increase prevails over acidification in gene expression modulation of amastigote differentiation in Leishmania infantum

被引:52
作者
Alcolea P.J. [1 ]
Alonso A. [1 ]
Gómez M.J. [2 ]
Sánchez-Gorostiaga A. [1 ]
Moreno-Paz M. [2 ]
González-Pastor E. [2 ]
Toraño A. [3 ]
Parro V. [2 ]
Larraga V. [1 ]
机构
[1] Departamento de Microbiología Molecular y Biología de las Infecciones, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), 28040 Madrid
[2] Laboratorio de Ecología Molecular and Unidad de Secuenciación y Bioinformática, Centro de Astrobiología, Instituto Nacional de Técnica Aeroespacial Esteban Terradas (INTA) and CSIC, 28850, Torrejón de Ardoz, carretera de Ajalvir
[3] Servicio de Inmunología, Centro Nacional de Microbiología, Virología e Inmunología Sanitarias Instituto de Salud Carlos III (ISCIII), Majadahonda, carretera Majadahonda-Pozuelo
关键词
Culture Condition; Intracellular Amastigotes; Trypanothione Reductase; Axenic Amastigotes; Amastigote Stage;
D O I
10.1186/1471-2164-11-31
中图分类号
学科分类号
摘要
Background: The extracellular promastigote and the intracellular amastigote stages alternate in the digenetic life cycle of the trypanosomatid parasite Leishmania. Amastigotes develop inside parasitophorous vacuoles of mammalian phagocytes, where they tolerate extreme environmental conditions. Temperature increase and pH decrease are crucial factors in the multifactorial differentiation process of promastigotes to amastigotes. Although expression profiling approaches for axenic, cell culture- and lesion-derived amastigotes have already been reported, the specific influence of temperature increase and acidification of the environment on developmental regulation of genes has not been previously studied. For the first time, we have used custom L. infantum genomic DNA microarrays to compare the isolated and the combined effects of both factors on the transcriptome.Results: Immunofluorescence analysis of promastigote-specific glycoprotein gp46 and expression modulation analysis of the amastigote-specific A2 gene have revealed that concomitant exposure to temperature increase and acidification leads to amastigote-like forms. The temperature-induced gene expression profile in the absence of pH variation resembles the profile obtained under combined exposure to both factors unlike that obtained for exposure to acidification alone. In fact, the subsequent fold change-based global iterative hierarchical clustering analysis supports these findings.Conclusions: The specific influence of temperature and pH on the differential regulation of genes described in this study and the evidence provided by clustering analysis is consistent with the predominant role of temperature increase over extracellular pH decrease in the amastigote differentiation process, which provides new insights into Leishmania physiology. © 2010 Alcolea et al; licensee BioMed Central Ltd.
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