STABLE TRANSFECTION OF MALARIA PARASITE BLOOD STAGES

被引：196

作者：

VANDIJK, MR ^{[1
]}

WATERS, AP ^{[1
]}

JANSE, CJ ^{[1
]}

机构：

[1] LEIDEN UNIV, DEPT PARASITOL, 2300 RC LEIDEN, NETHERLANDS

来源：

SCIENCE | 1995年 / 268卷 / 5215期

关键词：

D O I：

10.1126/science.7761856

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Genetic manipulation of malaria parasites would revolutionize the study of this group of pathogens and have implications for vaccine and drug development. This report describes the stable, drug-selectable genetic transformation of the clinically relevant intracellular blood stages of a malaria parasite. A plasmid transfection vector carrying the gene locus that encodes a drug-resistant form of the bifunctional enzyme dihydrofolate reductase-thymidylate synthase from the rodent malaria parasite Plasmodium berghei was constructed. Derivatives of this vector were introduced into merozoites of P. berghei by electroporation, and parasites were selected for successful transformation in the rodent host on the basis of resistance to pyrimethamine. The plasmids were present in a circular, unrearranged form that replicated episomally to an observed maximum of 15 copies per cell in drug-resistant populations.

引用

页码：1358 / 1362

页数：5

共 29 条

[1] STABLE TRANSFORMATION OF LEPTOMONAS-SEYMOURI BY CIRCULAR EXTRACHROMOSOMAL ELEMENTS [J].

BELLOFATTO, V ;

TORRESMUNOZ, JE ;

CROSS, GAM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (15) :6711-6715

[2] AMINO-ACID CHANGES LINKED TO PYRIMETHAMINE RESISTANCE IN THE DIHYDROFOLATE-REDUCTASE THYMIDYLATE SYNTHASE GENE OF PLASMODIUM-FALCIPARUM [J].

COWMAN, AF ;

MORRY, MJ ;

BIGGS, BA ;

CROSS, GAM ;

FOOTE, SJ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (23) :9109-9113

[3] CHROMOSOMAL REARRANGEMENTS AND POINT MUTATIONS IN THE DHFR-TS GENE OF PLASMODIUM-CHABAUDI UNDER ANTIFOLATE SELECTION [J].

COWMAN, AF ;

LEW, AM .

MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 1990, 42 (01) :21-29

[4] GENE REPLACEMENT IN PARASITIC PROTOZOA [J].

CRUZ, A ;

BEVERLEY, SM .

NATURE, 1990, 348 (6297) :171-173

[5] HOMOLOGOUS RECOMBINATION AND GENE REPLACEMENT AT THE DIHYDROFOLATE REDUCTASE-THYMIDYLATE SYNTHASE LOCUS IN TOXOPLASMA-GONDII [J].

DONALD, RGK ;

ROOS, DS .

MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 1994, 63 (02) :243-253

[6] STABLE MOLECULAR-TRANSFORMATION OF TOXOPLASMA-GONDII - A SELECTABLE DIHYDROFOLATE REDUCTASE-THYMIDYLATE SYNTHASE MARKER BASED ON DRUG-RESISTANCE MUTATIONS IN MALARIA [J].

DONALD, RGK ;

ROOS, DS .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (24) :11703-11707

[7] ORGANIZATION OF SUBTELOMERIC REPEATS IN PLASMODIUM-BERGHEI [J].

DORE, E ;

PACE, T ;

PONZI, M ;

PICCI, L ;

FRONTALI, C .

MOLECULAR AND CELLULAR BIOLOGY, 1990, 10 (05) :2423-2427

[8] STABLE INTEGRATIVE TRANSFORMATION OF TRYPANOSOMA-BRUCEI THAT OCCURS EXCLUSIVELY BY HOMOLOGOUS RECOMBINATION [J].

EID, J ;

SOLLNERWEBB, B .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (06) :2118-2121

[9] TRANSFECTION OF THE MALARIA PARASITE AND EXPRESSION OF FIREFLY LUCIFERASE [J].

GOONEWARDENE, R ;

DAILY, J ;

KASLOW, D ;

SULLIVAN, TJ ;

DUFFY, P ;

CARTER, R ;

MENDIS, K ;

WIRTH, D .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (11) :5234-5236

[10] HOST-CELL SPECIFICITY AND SCHIZOGONY OF PLASMODIUM-BERGHEI UNDER DIFFERENT INVITRO CONDITIONS [J].

JANSE, CJ ;

BOORSMA, EG ;

RAMESAR, J ;

GROBBEE, MJ ;

MONS, B .

INTERNATIONAL JOURNAL FOR PARASITOLOGY, 1989, 19 (05) :509-514

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