Characterization of the switch of kinetoplast DNA minicircle dominance during development and reversion of drug resistance in Leishmania

Lee, Sho-Tone; Tarn, Chi; Chang, Kwang-Poo

doi:10.1016/0166-6851(93)90041-u

Cited by 33 publications

(18 citation statements)

References 30 publications

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“…Minicircles are present in each cell in multiple copies (Lee et al 1993), thus leading to a higher sensitivity, which is often required for detection of Leishmania in clinical specimens. Kinetoplast minicircle DNA of Trypanosoma is known to be polymorphic (Rogers and Wirth 1988;Stuart 1983); however, especially in Leishmania, the extent on the nucleotide levels is poorly described.…”

Section: Introductionmentioning

confidence: 99%

“…Kinetoplast minicircle DNA of Trypanosoma is known to be polymorphic (Rogers and Wirth 1988;Stuart 1983); however, especially in Leishmania, the extent on the nucleotide levels is poorly described. Except for L. mexicana amazonensis (Rogers and Wirth 1988;Lee et al 1993) and L tarentolae (Kidane et al 1984), R Dobner -T. L6scher 9 H. Rinder (~) Abteilung for Infektions-und Tropenmedizin, Universit~t Mtinchen, Leopoldstrasse 5, D-80802 Mtinchen, Germany published sequences of Leishmania minicircle DNA report only single examples for each species (Barker et al 1986;Smith et al 1989;Laskay et al 1991;Blackwell 1992;de Bruijn and Barker 1992).…”

Section: Introductionmentioning

confidence: 99%

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Intra- and interspecific polymorphisms ofLeishmania donovani andL. tropica minicircle DNA

1994

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A pair of degenerate polymerase chain reac-TT ACA CC) defining a 0.15-kb segment of Leishmania minicircle DNA was constructed. These primers amplified not only inter-but also intraspecifically polymorphic sequences. Individual sequences revealed a higher intraspecific than interspecific divergence. It is concluded that individual sequences are of limited relevance for species determination. In contrast, when a data base of 19 different sequences was analyzed in a dendrographic plot, an accurate species differentiation was feasible.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Intra- and interspecific polymorphisms ofLeishmania donovani andL. tropica minicircle DNA

1994

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“…The switch is not due to selection of a particular parasite population bearing that specific class of minicircle but rather to a process during which the predominant wild-type minicircles are replaced by certain preexisting minor sequences to become dominant in the same network. This has been demonstrated by minicircle-specific endonuclease treatment combined with electron-microscopic examination of the kDNA networks (13). During such dynamic switching, the network structure is not disrupted, at least according to results of DAPI (4',6'-diamidino-2-phenylindole) staining of the cells.…”

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confidence: 96%

“…Subsequent cloning and sequencing of kDNA maxicircles (14) and minicircles (13) from repeatedly cloned parasites before and after drug resistance selection indicate that the change in maxicircles is due to base replacements and insertion/deletion of nucleotide sequences whereas the change in minicircles is due to preferential selection of * Corresponding author. Phone: 886-2-7899170.…”

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confidence: 99%

“…The switch in replication from one class of minicircle to another occurs within a narrow range of drug and in three to four passages during stepwise drug resistance selection (13). The switch is not due to selection of a particular parasite population bearing that specific class of minicircle but rather to a process during which the predominant wild-type minicircles are replaced by certain preexisting minor sequences to become dominant in the same network.…”

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Selection for arsenite resistance causes reversible changes in minicircle composition and kinetoplast organization in Leishmania mexicana.

et al. 1994

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Certain minor minicircle sequence classes in the kinetoplast DNA (kDNA) networks of arsenite-or tunicamycin-resistant Leishmania mexicana amazonensis variants whose nuclear DNA is amplified appear to be preferentially selected to replicate (S. T. Lee, C. Tarn, and K. P. Chang, Mol. Biochem. Parasitol. 58:187-204, 1993). These sequences replace the predominant wild-type minicircle sequences to become dominant species in the kDNA network. The switch from wild-type-specific to variant-specific minicircles takes place rapidly within the same network, the period of minicircle dominance changes being defined as the transition period. To investigate the structural organization of the kDNA networks during this transition period, we analyzed kDNA from whole arsenite-resistant Leishmania parasites by dot hybridization with sequence-specific DNA probes and by electron-microscopic examination of isolated kDNA networks in vitro. Both analyses concluded that during the switch of dominance the predominant wild-ype minicircle class was rapidly lost and that selective replication of variant-specific minicircles subsequently filled the network step by step. There was a time during the transition when few wild-type-or variant-specific minicircles were present, leaving the network almost empty and exposing a species of thick, long, fibrous DNA which seemed to form a skeleton for the network. Both minicircles and maxicircles were found to attach to these long DNA fibrils. The nature of the long DNA fibrils is not clear, but they may be important in providing a framework for the network structure and a support for the replication of minicircles and maxicircles.

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Arsenite Resistance in Leishmania and Possible Drug Targets

Singh

Jayanarayan

Dey

Advances in Experimental Medicine and Biology

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Pregarded as the second-most dreaded parasitic disease after malaria (WHO). Visceral leishmaniasis or kala-azar, caused by Leishmania donovani, is the most fatal form of leishmaniasis afflicting millions of people worldwide. No vaccination is available against leishmaniasis and fast spreading drug resistance in these parasitic organisms is posing a major medical threat. All these emphasize the need for new drugs and molecular targets along with reappraisal of existing therapeutics. Identification and characterization of cellular targets and answering the problem of drug resistance in Leishmania has always been the main thrust of protozoal research worldwide. Model drug resistance phenotypes against drugs, viz. arsenite (an antimony related metal ion, the first line of treatment against leishmaniasis), have been widely used to address and understand mechanism of drug resistance. The present discussion is an attempt to understand the different factors associated with arsenite resistance in Leishmania.

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Characterization of the switch of kinetoplast DNA minicircle dominance during development and reversion of drug resistance in Leishmania

Cited by 33 publications

References 30 publications

Intra- and interspecific polymorphisms ofLeishmania donovani andL. tropica minicircle DNA

Intra- and interspecific polymorphisms ofLeishmania donovani andL. tropica minicircle DNA

Selection for arsenite resistance causes reversible changes in minicircle composition and kinetoplast organization in Leishmania mexicana.

Arsenite Resistance in Leishmania and Possible Drug Targets

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