Differential gene expression analysis in antimony-unresponsive Indian kala azar (visceral leishmaniasis) clinical isolates by DNA microarray
2007; Cambridge University Press; Volume: 134; Issue: 6 Linguagem: Inglês
10.1017/s0031182007002284
ISSN1469-8161
AutoresNeeloo Singh, Renata Almeida, Hema Kothari, Pranav Kumar, Goutam Mandal, Mitali Chatterjee, V. Subramanian, Madabosse K Govind, Sunil K. Mandal, Shyam Sundar,
Tópico(s)Research on Leishmaniasis Studies
ResumoSUMMARY In this study, cDNA microarray analysis of a closely related species, Leishmania major , was used as a screening tool to compare antimonial-resistant and susceptible clinical isolates of Leishmania donovani in order to to identify candidate genes on the basis of antimony resistance. Clinically confirmed resistant isolate 39 and sensitive isolate 2001 were used in this study. Many differentially regulated genes were identified whose expression levels differ in sodium antimony gluconate (SAG)-treated patients. Interestingly, genes on the array, showing changes in expression of over 2-fold revealed the identity of ABC transporters, which are known determinants of drug resistance in laboratory mutants. The functionality of the transporters was validated by flow cytometry which, being biologically informative, provides direct clues to gene function. The results suggest that isolate 39 could have developed resistance by an increased multidrug resistance protein (MRP)-like pump. This study provides preliminary clues to the role of a thiol-dependent efflux system in antimonial resistant clinical isolates of Leishmania donovani .
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