Institute of Tropical Medicine Antwerp
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Characterisation of antimony-resistant Leishmania donovani isolates: biochemical and biophysical studies and interaction with host cells

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Show simple item record Mukhopadhyay, R. Mukherjee, S. Mukherjee, B. Naskar, K. Mandal, D. Decuypere, S. Ostyn, B. Prajapati, V. K. Sundar, S. Dujardin, J. C. Roy, S. 2011-12-15T10:52:15Z 2011-12-15T10:52:15Z 2011
dc.identifier.issn 0020-7519
dc.identifier.other ITG-P6B
dc.identifier.other ITG-H7B
dc.identifier.other ITG-P10A
dc.identifier.other MULTI
dc.identifier.other PARAS
dc.identifier.other U-PROTO
dc.identifier.other HEALTH
dc.identifier.other U-EPID
dc.identifier.other JIF
dc.identifier.other DOI
dc.identifier.other Abstract
dc.identifier.other UPD41
dc.description.abstract Recent clinical isolates of Leishmania donovani from the hyperendemic zone of Bihar were characterised in vitro in terms of their sensitivity towards sodium stibogluconate (SSG) in a macrophage (MPhi) culture system. The resulting half maximal effective concentration (EC(50)) values were compared with those of known sensitive isolates. Fifteen of the isolates showed decreased sensitivity towards SSG with an average EC(50) of 25.7+/-4.5mug/ml pentavalent antimony (SbV) (defined as antimony resistant (Sb-R)), whereas nine showed considerable sensitivity with an average EC(50) of 4.6+/-1.7mug/ml (defined as antimony sensitive (Sb-S)). Out of those nine, seven were recent clinical isolates and the remaining two were known sensitive isolates. Compared with the Sb-S, Sb-R isolates showed enhanced expression of thiol metabolising enzymes in varying degrees coupled with increased intracellular non-protein thiol content, decreased fluorescence anisotropy (inversely proportional with membrane fluidity) and over-expression of the terminal glycoconjugates (N-acetyl-d-galactosaminyl residue). MPhis infected with Sb-R but not with Sb-S showed up-regulation of the ATP Binding Cassette transporter multidrug resistance protein 1 (MRP1) and permeability glycoprotein (P-gp), while the supernatant contained abundant IL-10. The above results reinforce the notion that Sb-R parasites have undergone a number of biochemical and biophysical changes as part of their adaptation to ensure their survival in the host. en
dc.language English en
dc.subject Protozoal diseases en
dc.subject Visceral en
dc.subject Leishmaniasis en
dc.subject Kala azar en
dc.subject Leishmania donovani en
dc.subject Vectors en
dc.subject Sandflies en
dc.subject Phlebotomus argentipes en
dc.subject Characterization en
dc.subject Isolation en
dc.subject In vitro en
dc.subject Drug susceptibility en
dc.subject Sensitivity en
dc.subject Antimony en
dc.subject Sodium stibogluconate en
dc.subject Interactions en
dc.subject India en
dc.subject Asia, South en
dc.title Characterisation of antimony-resistant Leishmania donovani isolates: biochemical and biophysical studies and interaction with host cells en
dc.type Article en
dc.citation.issue 13-14 en
dc.citation.jtitle International Journal for Parasitology en
dc.citation.volume 41 en
dc.citation.pages 1311-1321 en
dc.citation.jabbreviation Int J Parasitol en

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