Multiple cytochrome B mutations may cause atovaquone resistance.
نویسندگان
چکیده
Phillips and Lampe [1]. Given the rapid changes in HAART over the past decade— including marked improvements in potency, tolerability, and dosing frequency, it is doubtful that we will ever have an observational cohort in which patients receive the same therapy for 10 years. New therapies are certain to emerge that will be adopted, and the details of the research questions will change over time.
منابع مشابه
Cytochrome b mutations that modify the ubiquinol-binding pocket of the cytochrome bc1 complex and confer anti-malarial drug resistance in Saccharomyces cerevisiae.
Atovaquone is a new anti-malarial agent that specifically targets the cytochrome bc1 complex and inhibits parasite respiration. A growing number of failures of this drug in the treatment of malaria have been genetically linked to point mutations in the mitochondrial cytochrome b gene. To better understand the molecular basis of atovaquone resistance in malaria, we introduced five of these mutat...
متن کاملMutations in Plasmodium falciparum cytochrome b that are associated with atovaquone resistance are located at a putative drug-binding site.
Atovaquone is the major active component of the new antimalarial drug Malarone. Considerable evidence suggests that malaria parasites become resistant to atovaquone quickly if atovaquone is used as a sole agent. The mechanism by which the parasite develops resistance to atovaquone is not yet fully understood. Atovaquone has been shown to inhibit the cytochrome bc(1) (CYT bc(1)) complex of the e...
متن کاملRecapitulation in Saccharomyces cerevisiae of cytochrome b mutations conferring resistance to atovaquone in Pneumocystis jiroveci.
Pneumocystis jiroveci (human-derived P. carinii) is an opportunistic pathogenic fungus which causes pneumonia and is life-threatening in immunocompromised individuals. Spontaneously acquired resistance to atovaquone, a hydroxynaphthoquinone that is used to treat P. jiroveci infections, was linked to mutations in the mitochondrially encoded cytochrome b gene. Because P. jiroveci cannot be easily...
متن کاملMolecular basis for atovaquone resistance in Pneumocystis jirovecii modeled in the cytochrome bc(1) complex of Saccharomyces cerevisiae.
Atovaquone is a substituted hydroxynaphthoquinone that is widely used to prevent and clear Plasmodium falciparum malaria and Pneumocystis jirovecii pneumonia. Atovaquone inhibits respiration in target organisms by specifically binding to the ubiquinol oxidation site at center P of the cytochrome bc(1) complex. The failure of atovaquone treatment and mortality of patients with malaria and P. jir...
متن کاملMolecular basis of Toxoplasma gondii atovaquone resistance modeled in Saccharomyces cerevisiae.
0 d ondii is a widespread disease affecting primarily immunocomromised and pregnant individuals [1]. Atovaquone is a recently ntroduced anti-malarial compound with broad spectrum activty against various apicomplexan parasites [2–5] including T. ondii [6]. Approved by the FDA in 1995, this drug is a potent nd specific inhibitor of the cytochrome bc1 complex [7], an ssential respiratory enzyme pr...
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عنوان ژورنال:
- The Journal of infectious diseases
دوره 191 5 شماره
صفحات -
تاریخ انتشار 2005