Have malaria parasites three genomes?

Wilson, Robert; Gardner, Malcolm J.; Feagin, Jean E.; Williamson, D. H.

doi:10.1016/0169-4758(91)90276-t

Cited by 74 publications

(22 citation statements)

References 28 publications

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“…Although these drugs are known to affect organellar ribosomes in various systems (11), it has not been possible to demonstrate any effect of clindamycin or azithromycin on mitochondrial protein synthesis (20). It is intriguing, however, that apicomplexan parasites possess a novel extrachromosomal element containing prokaryotic-type ribosomal genes (1,8,28).…”

Section: Fig 10mentioning

confidence: 99%

In vitro assays elucidate peculiar kinetics of clindamycin action against Toxoplasma gondii

Fichera

Bhopale

Roos

1995

Antimicrob Agents Chemother

180

129

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In order to characterize the delayed effect of clindamycin and macrolide antibiotics against Toxoplasma gondii tachyzoites (E. R. Pfefferkorn and S. E. Borotz, Antimicrob. Agents Chemother. 38:31-37, 1994), we have carefully examined the replication of parasites as a function of time after drug addition. Intracellular tachyzoites treated with up to 20 M clindamycin (>1,000 times the 50% inhibitory concentration) exhibit doubling times indistinguishable from those of controls (ϳ7 h). Drug-treated parasites emerge from infected cells and establish parasitophorous vacuoles inside new host cells as efficiently as untreated controls, but replication within the second vacuole is dramatically slowed. Growth inhibition in the second vacuole does not require continued presence of drug, but it is dependent solely on the concentration and duration of drug treatment in the first (previous) vacuole. The susceptibility of intracellular parasites to nanomolar concentrations of clindamycin contrasts with that of extracellular tachyzoites, which are completely resistant to treatment, even through several cycles of subsequent intracellular replication. This peculiar phenotype, in which drug effects are observed only in the second infectious cycle, also characterizes azithromycin and chloramphenicol treatment, but not treatment with cycloheximide, tetracycline, or anisomycin. These findings provide new insights into the mode of clindamycin and macrolide action against T. gondii, although the relevant target for their action remains unknown.The protozoan parasite Toxoplasma gondii is a ubiquitous human pathogen long recognized as a source of congenital neurological abnormalities (19). In recent years, this parasite has also acquired considerable notoriety as an opportunistic infection associated with AIDS (16). The ability of T. gondii parasites to persist as latent cysts in the tissues of infected patients mandates chronic treatment for infected AIDS patients, to guard against recrudescence. Unfortunately, the traditional therapeutic regimen of pyrimethamine plus sulfonamides (18) is not always suitable for prolonged treatment, because of the emergence of sulfa hypersensitivity and other adverse side effects (12,14,27).Clindamycin (a lincosamide) and several macrolide antibiotics have proven effective for the treatment of AIDS-toxoplasmosis, usually in combination with pyrimethamine (6, 13, 15). These compounds are known to block protein synthesis in bacteria by interacting with the peptidyl transferase domain of 23S rRNA (5), but their target in T. gondii and related parasites remains unclear (1). Early difficulties in establishing a functional in vitro system to study clindamycin and macrolide action against T. gondii (4, 9, 17) can now be explained by the long lag period between drug administration and effect (20,21). Nanomolar drug concentrations block parasite replication, but only 2 to 3 days after treatment-a remarkable delay, considering that the tachyzoite undergoes ϳ8 generations in this time.In order to more precisely e...

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Section: Fig 10mentioning

confidence: 99%

In vitro assays elucidate peculiar kinetics of clindamycin action against Toxoplasma gondii

Fichera

Bhopale

Roos

1995

Antimicrob Agents Chemother

180

129

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“…The malaria protozoa contain two more genomes other than in the nuclear chromosomes; two extra chromosomal DNA molecules of the 35-kbp circular DNA called the plastid genome and the approximate 6-kbp element of the mitochondrial genome (Wilson et al 1991). Until recently, the mitochondrial genomes of Plasmodium vivax and P. falciparum were completely sequenced and analyzed for the structure (Sharma et al 1998(Sharma et al , 2001Conway et al 2000).…”

Section: Introductionmentioning

confidence: 99%

Complete nucleotide sequences of the mitochondrial genomes of two avian malaria protozoa, Plasmodium gallinaceum and Plasmodium juxtanucleare

et al. 2006

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We analyzed mitochondrial genomes of two avian malaria protozoa, Plasmodium gallinaceum and Plasmodium juxtanucleare. Both mitochondrial genomes were estimated to be 6,002 and 6,014 bp in length, respectively, and to have the identical gene organization and contents to that of other Plasmodium species previously analyzed; three functional genes for cytochrome c oxidase subunit I, III, and cytochrome (cyt b), with following sets of discontinuous and scrambled 15 ribosomal subunit RNA (rRNA) genes. Similarities of the three protein-coding genes showed closer relationship within avian malaria protozoa rather than mammalian Plasmodium species. In addition, we showed the tandem repeated structure of each mitochondrial genome of both P. gallinaceum and P. juxtanucleare as well as previously found in mammalian Plasmodium species. This study revealed the complete sequences and structure of the mitochondrial genomes of avian malaria protozoa for the first time.

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“…In P. falciparum, there are also two organellar genomes. The mitochondrial genome is a 5.9-kb tandemly repeated DNA molecule, and there is also a 35-kb circular DNA molecule carrying genes that are normally associated with plastid genomes (206). Chromosome 2, containing about 209 protein-encoding genes, was sequenced in 1998 (61), and chromosome 3, which carries 215 genes, was sequenced in 1999 (19).…”

Section: Malaria Genome Projectmentioning

confidence: 99%

Current Status of Malaria and Potential for Control

2001

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Malaria remains one of the world's worst health problems with 1.5 to 2.7 million deaths annually; these deaths are primarily among children under 5 years of age and pregnant women in sub-Saharan Africa. Of significance, more people are dying from malaria today than 30 years ago. This review considers the factors which have contributed to this gloomy picture, including those which relate to the vector, the female anopheline mosquito; to human activity such as creating new mosquito breeding sites, the impact of increased numbers of people, and how their migratory behavior can increase the incidence and spread of malaria; and the problems of drug resistance by the parasites to almost all currently available antimalarial drugs. In a selective manner, this review describes what is being done to ameliorate this situation both in terms of applying existing methods in a useful or even crucial role in control and prevention and in terms of new additions to the antimalarial armory that are being developed. Topics covered include biological control of mosquitoes, the use of insecticide-impregnated bed nets, transgenic mosquitoes manipulated for resistance to malaria parasites, old and new antimalarial drugs, drug resistance and how best to maintain the useful life of antimalarials, immunity to malaria and the search for antimalarial vaccines, and the malaria genome project and the potential benefits to accrue from it

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Have malaria parasites three genomes?

Cited by 74 publications

References 28 publications

In vitro assays elucidate peculiar kinetics of clindamycin action against Toxoplasma gondii

In vitro assays elucidate peculiar kinetics of clindamycin action against Toxoplasma gondii

Complete nucleotide sequences of the mitochondrial genomes of two avian malaria protozoa, Plasmodium gallinaceum and Plasmodium juxtanucleare

Current Status of Malaria and Potential for Control

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