A Proteomic screen implicates HSP83 and a small kinetoplastid calpain-related protein in drug resistance in Leishmania donovani clinical field isolates by modulating drug-induced programmed cell death

doi:10.1074/mcp.M600319-MCP200

HOME

QUICK SEARCH:

	Author:		Keyword(s):
Year:		Vol:		Page:

A more recent version of this article appeared on January 1, 2007.

This Article

	Full Text (PDF)
	All Versions of this Article: M600319-MCP200v1 6/1/88 most recent
	Submit a response
	Alert me when this article is cited
	Alert me when eLetters are posted
	Alert me if a correction is posted

Services

	Email this article to a friend
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new issues of the journal
	Download to citation manager
	Glossary


Citing Articles

	Citing Articles via HighWire
	Citing Articles via Google Scholar

Google Scholar

	Articles by Vergnes, B.
	Articles by Ouellette, M.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Vergnes, B.
	Articles by Ouellette, M.

Social Bookmarking

	What's this?

Submitted on August 17, 2006
Revised on October 16, 2006
Accepted on October 17, 2006

A Proteomic screen implicates HSP83 and a small kinetoplastid calpain-related protein in drug resistance in Leishmania donovani clinical field isolates by modulating drug-induced programmed cell death

Baptiste Vergnes, Benjamin Gourbal, Isabelle Girard, Shyam Sundar, Jolyne Drummelsmith, and Marc Ouellette

Research Center in Infectious Diseases, RC709, CHUL Research Center, Quebec, Quebec G1V 4G2

Corresponding Author: marc.ouellette{at}crchul.ulaval.ca

The therapeutic mainstay against the protozoan parasite Leishmania is still based on the antiquated pentavalent antimonials (SbV) but resistance is increasing in several parts of the world. Resistance is now partly understood in laboratory isolates but our understanding of resistance in field isolates is lagging behind. We describe here a comparative analysis of a genetically related pair of SbV-sensitive and –resistant L. donovani strains isolated from kala-azar patients. The resistant isolate exhibited cross resistance to other unrelated Leishmania drugs including miltefosine and amphotericin B. A comparative proteomic screen has highlighted a number of proteins differentially expressed suggesting that programmed cell death (PCD) is modified in the resistant parasite. Indeed, drug-induced PCD progression is altered in the SbV-resistant strain as determined using early and late markers of apoptosis. Two proteins, the heat shock protein HSP83 and the small kinetoplastid calpain-related protein (SKCRP14.1) were shown to be intimately implicated in the drug-induced PCD phenotype. HSP83 increases drug resistance and reduces drug-mediated PCD activation by interfering with the mitochondrial membrane potential while SKCRP14.1 promotes antimonial-induced PCD but protects against miltefosine-induced PCD. This study highlights the important role of PCD in drug susceptibility/resistance in the protozoan parasite Leishmania.

Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

J. Mookerjee Basu, A. Mookerjee, R. Banerjee, M. Saha, S. Singh, K. Naskar, G. Tripathy, P. K. Sinha, K. Pandey, S. Sundar, et al.
Inhibition of ABC Transporters Abolishes Antimony Resistance in Leishmania Infection
Antimicrob. Agents Chemother., March 1, 2008; 52(3): 1080 - 1093.
[Abstract] [Full Text] [PDF]

K. El Fadili, M. Imbeault, N. Messier, G. Roy, B. Gourbal, M. Bergeron, M. J. Tremblay, D. Legare, and M. Ouellette
Modulation of Gene Expression in Human Macrophages Treated with the Anti-Leishmania Pentavalent Antimonial Drug Sodium Stibogluconate
Antimicrob. Agents Chemother., February 1, 2008; 52(2): 526 - 533.
[Abstract] [Full Text] [PDF]

J. R. Luque-Ortega and L. Rivas
Miltefosine (Hexadecylphosphocholine) Inhibits Cytochrome c Oxidase in Leishmania donovani Promastigotes
Antimicrob. Agents Chemother., April 1, 2007; 51(4): 1327 - 1332.
[Abstract] [Full Text] [PDF]

All ASBMB Journals	Journal of Biological Chemistry
Journal of Lipid Research	ASBMB Today

				K. El Fadili, M. Imbeault, N. Messier, G. Roy, B. Gourbal, M. Bergeron, M. J. Tremblay, D. Legare, and M. Ouellette Modulation of Gene Expression in Human Macrophages Treated with the Anti-Leishmania Pentavalent Antimonial Drug Sodium Stibogluconate Antimicrob. Agents Chemother., February 1, 2008; 52(2): 526 - 533. [Abstract] [Full Text] [PDF]

				J. R. Luque-Ortega and L. Rivas Miltefosine (Hexadecylphosphocholine) Inhibits Cytochrome c Oxidase in Leishmania donovani Promastigotes Antimicrob. Agents Chemother., April 1, 2007; 51(4): 1327 - 1332. [Abstract] [Full Text] [PDF]