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1.
J Eukaryot Microbiol ; 69(6): e12906, 2022 11.
Article in English | MEDLINE | ID: mdl-35315174

ABSTRACT

Toxoplasma gondii is a member of the apicomplexan phylum, a group of single-celled eukaryotic parasites that cause significant human morbidity and mortality around the world. T. gondii harbors two organelles of endosymbiotic origin: a non-photosynthetic plastid, known as the apicoplast, and a single mitochondrion derived from the ancient engulfment of an α-proteobacterium. Due to excitement surrounding the novelty of the apicoplast, the T. gondii mitochondrion was, to a certain extent, overlooked for about two decades. However, recent work has illustrated that the mitochondrion is an essential hub of apicomplexan-specific biology. Development of novel techniques, such as cryo-electron microscopy, complexome profiling, and next-generation sequencing have led to a renaissance in mitochondrial studies. This review will cover what is currently known about key features of the T. gondii mitochondrion, ranging from its genome to protein import machinery and biochemical pathways. Particular focus will be given to mitochondrial features that diverge significantly from the mammalian host, along with discussion of this important organelle as a drug target.


Subject(s)
Apicoplasts , Parasites , Toxoplasma , Animals , Humans , Toxoplasma/metabolism , Cryoelectron Microscopy , Apicoplasts/metabolism , Mitochondria/metabolism , Mammals
2.
mBio ; 14(5): e0176923, 2023 Oct 31.
Article in English | MEDLINE | ID: mdl-37796022

ABSTRACT

IMPORTANCE: Members of the coiled-coil-helix-coiled-coil-helix (CHCH) domain protein family are transported into the mitochondrial intermembrane space, where they play important roles in the biogenesis and function of the organelle. Unexpectedly, the ATP synthase of the apicomplexan Toxoplasma gondii harbors CHCH domain-containing subunits of unknown function. As no other ATP synthase studied to date contains this class of proteins, characterizing their function will be of broad interest to the fields of molecular parasitology and mitochondrial evolution. Here, we demonstrate that that two T. gondii ATP synthase subunits containing CHCH domains are required for parasite survival and for stability and function of the ATP synthase. We also show that knockdown disrupts multiple aspects of the mitochondrial morphology of T. gondii and that mutation of key residues in the CHCH domains caused mis-localization of the proteins. This work provides insight into the unique features of the apicomplexan ATP synthase, which could help to develop therapeutic interventions against this parasite and other apicomplexans, such as the malaria-causing parasite Plasmodium falciparum.


Subject(s)
Parasites , Toxoplasma , Animals , Toxoplasma/genetics , Toxoplasma/metabolism , Mitochondria/metabolism , Proteins/metabolism , Parasites/metabolism , Nitric Oxide Synthase/metabolism , Adenosine Triphosphate/metabolism , Protozoan Proteins/genetics , Protozoan Proteins/metabolism , Mitochondrial Proteins/metabolism
3.
Am J Trop Med Hyg ; 102(4): 827-831, 2020 04.
Article in English | MEDLINE | ID: mdl-32043449

ABSTRACT

Saint Lucia at one time had levels of schistosomiasis prevalence and morbidity as high as many countries in Africa. However, as a result of control efforts and economic development, including more widespread access to sanitation and safe water, schistosomiasis on the island has practically disappeared. To evaluate the current status of schistosomiasis in Saint Lucia, we conducted a nationally representative school-based survey of 8-11-year-old children for prevalence of Schistosoma mansoni infections using circulating antigen and specific antibody detection methods. We also conducted a questionnaire about available water sources, sanitation, and contact with fresh water. The total population of 8-11-year-old children on Saint Lucia was 8,985; of these, 1,487 (16.5%) provided urine for antigen testing, 1,455 (16.2%) provided fingerstick blood for antibody testing, and 1,536 (17.1%) answered the questionnaire. Although a few children were initially low positives by antigen or antibody detection methods, none could be confirmed positive by follow-up testing. Most children reported access to clean water and sanitary facilities in or near their homes and 48% of the children reported contact with fresh water. Together, these data suggest that schistosomiasis transmission has been interrupted on Saint Lucia. Additional surveys of adults, snails, and a repeat survey among school-age children will be necessary to verify these findings. However, in the same way that research on Saint Lucia generated the data leading to use of mass drug administration for schistosomiasis control, the island may also provide the information needed for guidelines to verify interruption of schistosomiasis transmission.


Subject(s)
Antibodies, Helminth/blood , Schistosomiasis/epidemiology , Schistosomiasis/transmission , Child , Female , Humans , Male , Risk Factors , Saint Lucia/epidemiology , Sanitation , Schistosomiasis/prevention & control , Serologic Tests , Surveys and Questionnaires
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