Affinage · Plasmodium

Showing PF3D7_MIT02300 — CYTB is a alias.

CYTB

PF3D7_MIT02300 · cytochrome b

Annotated
2026-09-08
79 papers in source corpus 19 papers cited in narrative 19 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PF3D7_MIT02300 (CYTB) encodes the cytochrome b subunit of the mitochondrial cytochrome bc1 complex (complex III) in Plasmodium, one of only three protein-coding genes on the minimal ~6-kb extrachromosomal mitochondrial element and the first mitochondrial sequence identified in malaria parasites (PMID:2779560, PMID:8459834). The gene is maternally inherited: single-oocyst analysis of mosquito-stage crosses showed uniparental transmission (PMID:8467535), and hybridization of purified P. gallinaceum gametes localized the 6-kb element to female but not male gametes (PMID:7935632). Catalytically, CYTB accepts electrons from ubiquinol at its quinol oxidation (Qo) site and relays them via the iron-sulfur protein (ISP) subunit, whose large-scale domain movement between CYTB-binding conformations is required for turnover; atovaquone acts by locking ISP in its CYTB-binding conformation (PMID:15917236). This activity is central to the mitochondrial cytochrome pathway of respiration, which CYTB mutations specifically perturb without affecting the salicylhydroxamic-acid-sensitive alternative pathway (PMID:11560411). CYTB is the molecular target of atovaquone and a broad set of other electron-transport-chain inhibitors: Qo-site point mutations — recurrently converging on codon 268 (Y268S/N/C) and including M133I, L144S, G280D, L271V, K272R, V284F — confer high-level resistance by reducing inhibitor binding affinity, lowering bc1 catalytic Vmax, raising Km for ubiquinol, and weakening the ISP–CYTB interaction, at a measurable fitness cost during erythrocytic growth (PMID:10593174, PMID:10898682, PMID:18248769, PMID:22282497, PMID:12121915). The conserved Qo-site tyrosine (Y268) both mediates strong van der Waals contact with atovaquone's hydroxynaphthoquinone ring and normally suppresses ROS generation, such that its mutation causes cytochrome b–ISP cross-linking, oxidative damage to the [2Fe-2S] cluster, and elevated ROS (PMID:21454570, PMID:29844160). Dependence on CYTB/ETC function is demonstrable by rescue with yeast DHODH, which renders parasites insensitive to CYTB inhibitors (PMID:21866942, PMID:40460517). Beyond the Qo site, the quinone reduction (Qi) site of CYTB is an independent druggable target that synergizes with Qo-site inhibitors (PMID:25336726).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1989 Medium

    Establishing that malaria parasites carry a mitochondrial cytochrome b sequence answered whether these organisms possess a functional cytochrome system at all.

    Evidence Gene sequencing and transcript analysis of a 6.2-kb extrachromosomal element in P. gallinaceum

    PMID:2779560

    Open questions at the time
    • Function of the encoded protein not directly tested
    • Catalytic activity inferred from sequence similarity only
  2. 1993 Medium

    Sequencing the minimal P. falciparum mitochondrial genome placed CYTB as one of only three encoded proteins and flagged its divergent quinone-binding sites as a potential drug-selectivity determinant.

    Evidence DNA sequencing and comparative structural modeling of the 6-kb element

    PMID:8459834

    Open questions at the time
    • Drug affinity predictions not experimentally validated in this study
    • No functional assay of the Qo/Qi sites
  3. 1994 High

    Genetic-cross and gamete-fractionation experiments settled the inheritance mode of the CYTB-bearing mitochondrial genome, showing it is uniparental and specifically maternal.

    Evidence SNP tracking across 59 oocysts and hybridization of purified male/female gametes

    PMID:7935632 PMID:8467535

    Open questions at the time
    • Mechanism enforcing maternal exclusion of paternal mitochondria not addressed
  4. 2001 High

    Selecting atovaquone-resistant parasites and mapping mutations to CYTB identified the cytochrome bc1 complex's ubiquinol oxidase activity as the drug's target and defined resistance loci around the Qo site.

    Evidence In vivo/in vitro resistance selection, gene sequencing, molecular modeling, and respirometry in P. berghei and P. falciparum

    PMID:10593174 PMID:10898682 PMID:11560411

    Open questions at the time
    • Structural basis of reduced binding inferred from modeling only at this stage
    • Direct enzymatic measurement of mutant bc1 not yet performed
  5. 2002 Medium

    A competitive-growth assay quantified the fitness cost of CYTB resistance mutations, showing that double Qo-site mutations impair electron transport and reduce erythrocytic-stage fitness in the absence of drug.

    Evidence Competitive growth assay of single vs. double CYTB mutants plus ubiquinone-interaction modeling

    PMID:12121915

    Open questions at the time
    • Fitness cost measured in vitro only
    • Molecular basis of impaired electron transport modeled, not measured
  6. 2005 High

    A bacterial reconstitution system provided direct mechanistic proof that atovaquone works by locking the ISP subunit against CYTB and that a Plasmodium-type ef-loop mutation causes resistance with a catalytic penalty.

    Evidence Site-directed mutagenesis of Rhodobacter cytochrome b with biophysical ISP-movement and bc1 activity assays

    PMID:15917236

    Open questions at the time
    • Demonstrated in bacterial surrogate rather than Plasmodium enzyme
    • Not all Plasmodium resistance residues tested
  7. 2011 High

    Mechanistic dissection of the Y268 mutation revealed why the conserved Qo-site tyrosine is both a drug-contact residue and a guard against ROS, explaining the collateral oxidative damage of resistance mutations.

    Evidence Bacterial cytochrome b mutagenesis with ROS and enzyme-activity assays; decoquinate resistance genetics with yeast-DHODH complementation and docking

    PMID:21454570 PMID:21866942

    Open questions at the time
    • ROS mechanism established in bacterial system
    • Distinct binding modes shown by docking, not co-structures
  8. 2014 High

    Direct biochemical assays on parasite bc1 complexes quantified how specific Qo-site mutations reduce catalytic turnover, raise ubiquinol Km, and weaken ISP retention, closing the loop from genetics to enzymology.

    Evidence Enzyme kinetics, Western blotting and expression analysis on a Y268S field isolate; DHO-cytochrome c reductase IC50 assays on isolated P. berghei mitochondria

    PMID:22282497 PMID:25264100

    Open questions at the time
    • No high-resolution structure of the resistant Plasmodium complex
    • Compensatory upregulation inferred from expression correlation
  9. 2014 Medium

    Identification of a Qi-site inhibitor established that CYTB's quinone-reduction site is a second druggable pocket that synergizes with Qo-site inhibition.

    Evidence Whole-cell screening, resistance selection with whole-genome sequencing, and drug combination synergy assays

    PMID:25336726

    Open questions at the time
    • Qi-site binding inferred from resistance mapping, not structural data
    • Synergy mechanism not resolved
  10. 2025 Medium

    A succession of new chemotypes confirmed CYTB as a recurrently exploited antimalarial target across life-cycle stages, distinguished by variant Qo binding poses and validated by ETC-dependence rescue.

    Evidence Resistance selection, whole-genome sequencing, mitochondrial biosensor/complex III assays, yeast-DHODH complementation, and transmission-blocking/in vivo models for WJM228, PyAz90, and gamhepathiopine

    PMID:29844160 PMID:36853190 PMID:39483245 PMID:40460517

    Open questions at the time
    • Binding poses inferred from docking and cross-resistance rather than co-crystal structures
    • Full mutation-selectivity landscape across chemotypes incomplete

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution experimental structure of the Plasmodium CYTB-containing bc1 complex bound to inhibitors, and the in vivo mechanism enforcing maternal inheritance of its mitochondrial genome, remain unresolved.
  • No atomic-resolution structure of the parasite complex
  • Inheritance mechanism uncharacterized
  • Interplay between resistance mutations and stage-specific fitness incompletely mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
IRON-SULFUR PROTEIN (ISP/RIESKE) SUBUNIT OF COMPLEX III [#8, #12]UBIQUINOL/UBIQUINONE (SUBSTRATE AT QO AND QI SITES) [#7, #12, #14]
Complex memberships
Mitochondrial cytochrome bc1 complex (complex III), catalytic cytochrome b subunit [#8, #12, #13]

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 The cytochrome b gene (CYTB) in Plasmodium gallinaceum was identified on a 6.2-kb multimeric extrachromosomal element. The amino acid translation showed significant similarity to cytochrome b sequences from yeast, mammal, and fungus. The CYTB transcript is part of a larger primary transcript that is subsequently processed, producing a 1.2-kb message. This was the first identification of a mitochondrial nucleic acid sequence in malaria-causing organisms, suggesting a functional cytochrome system exists in these parasites. Gene sequencing, Southern blotting, RNA analysis of extrachromosomal element Molecular and cellular biology Medium 2779560
1993 Sequencing the P. falciparum 6-kb mitochondrial element revealed that CYTB encodes one of only three proteins in the minimal mt genome. Structural analysis of the predicted CYTB protein showed that the critical quinone binding sites (Qo and Qi) are divergent from those of other species, consistent with resistance to antimycin and related inhibitors, and with increased affinity for 8-aminoquinolines and hydroxynaphthoquinones. DNA sequencing, comparative structural analysis, molecular modeling Molecular and biochemical parasitology Medium 8459834
1993 Inheritance of the CYTB gene from the mitochondrial 6-kb element is uniparental in P. falciparum. Analysis of 59 individual hybrid oocysts from a cross in the mosquito demonstrated that inheritance of CYTB was not biparental. Single base-pair polymorphism marker in CYTB used to track inheritance in 59 oocysts from a mosquito-stage cross Current genetics High 8467535
1994 The uniparental inheritance of CYTB (mitochondrial 6-kb element) in malaria parasites is maternal. Purified male gametes of P. gallinaceum lacked hybridization signal for the 6-kb element probe, while female gametes were positive, demonstrating maternal transmission of the mitochondrial genome encoding CYTB. DNA hybridization of purified male and female gamete preparations with probes for 6-kb and 35-kb extrachromosomal DNAs Molecular and biochemical parasitology High 7935632
1999 Mutations in P. berghei CYTB confer resistance to atovaquone. Three mutations were detected: M133I or L144S at the Qo1 site (extramembranous amphipathic helix) and V284F in the sixth transmembrane helix. V284F was present in all resistant clones; additional Qo1 mutations significantly increased resistance. These results establish that atovaquone targets the ubiquinol oxidase activity of the cytochrome bc1 complex through interaction with CYTB. In vivo selection of resistant clones by escalating atovaquone doses; cytochrome b gene sequencing of resistant clones Molecular and biochemical parasitology High 10593174
2000 Point mutations in P. falciparum CYTB are associated with atovaquone resistance. Single or double amino acid mutations (including M133I, G280D) were detected in parasites surviving atovaquone in vitro and in a patient with treatment failure. These mutations confer a 25- to 9,354-fold reduction in susceptibility. Molecular modeling showed resistance-associated mutations cluster around the putative atovaquone-binding site of CYTB, consistent with reduced binding affinity. In vitro selection at increasing atovaquone concentrations; gene sequencing; molecular modeling of atovaquone-CYTB interaction Antimicrobial agents and chemotherapy High 10898682
2001 A point mutation in the P. falciparum CYTB gene associated with atovaquone resistance results in altered respiratory function: atovaquone inhibited total oxygen consumption by up to 66% in sensitive parasites but only up to 28% in resistant parasites. The resistant isolate showed no change in sensitivity to the alternative pathway inhibitor salicylhydroxamic acid, indicating CYTB mutation specifically alters cytochrome pathway sensitivity without affecting the alternative respiratory pathway. Oxygen consumption measurements in isogenic sensitive and resistant P. falciparum clinical isolate pair; pharmacological dissection with atovaquone and salicylhydroxamic acid Experimental parasitology Medium 11560411
2002 The double amino acid mutation M133I + G280D in P. falciparum CYTB, but not the single M133I mutation, is associated with a 5–9% loss of parasite fitness during erythrocytic stages in the absence of drug pressure. Molecular modeling predicted that G280D weakens the CYTB-ubiquinone complex due to proximity to the putative ubiquinone-binding site, reducing electron transport chain efficiency. Competitive growth fitness assay of atovaquone-resistant K1 clones with single vs. double CYTB mutations; molecular modeling of CYTB-ubiquinone interaction Antimicrobial agents and chemotherapy Medium 12121915
2005 Atovaquone blocks the large-scale domain movement of the iron-sulfur protein (ISP) subunit required for electron transfer in the cytochrome bc1 complex by locking ISP in its CYTB-binding conformation. Site-directed mutagenesis of bacterial cytochrome b at its ef loop to more closely resemble Plasmodium CYTB increased sensitivity to atovaquone. A mutation within the ef loop corresponding to a malaria atovaquone-resistance mutation rendered the bacterial complex resistant to atovaquone and caused a 10-fold reduction in in vitro complex activity, providing direct proof that the ef loop mutation causes atovaquone resistance. Site-directed mutagenesis of bacterial (Rhodobacter capsulatus) cytochrome b; biophysical and biochemical measurements of ISP domain movement; in vitro cytochrome bc1 complex activity assays The Journal of biological chemistry High 15917236
2007 Mutations at the Qo2 domain of P. berghei CYTB (Y268N, Y268C, L271V, K272R) confer atovaquone resistance. These extend previously identified Qo1 mutations and converge on codon 268, mirroring the most common resistance mutations in P. falciparum CYTB, confirming Qo2 as a key atovaquone interaction site in CYTB. In vivo selection of P. berghei resistant strains; cytochrome b gene sequencing Parasitology international Medium 18248769
2011 In vitro evolution of decoquinate-resistant P. falciparum parasites revealed two nonsynonymous mutations (A122T and Y126C) in CYTB within helix C of the ubiquinol-binding pocket. Transgenic parasites expressing yeast dihydroorotate dehydrogenase were >200-fold less sensitive to decoquinate, confirming CYTB/mitochondrial electron transport chain as decoquinate's target. Molecular docking showed decoquinate and atovaquone have distinctly different binding modes within the ubiquinol-binding site of CYTB. In vitro resistance evolution; comparative genomic analysis; transgenic parasite complementation with yeast DHODH; molecular docking ACS chemical biology High 21866942
2011 The Y268C mutation in CYTB (equivalent to the atovaquone-resistance mutation) causes the conserved tyrosine residue to be replaced by cysteine, leading to cross-linking between cytochrome b and iron-sulfur subunits, increased ROS production, and oxidative disruption of the catalytic [2Fe-2S] cluster. This tyrosine residue is essential for controlling unproductive encounters between O2 and catalytic intermediates at the quinol oxidation site to prevent ROS generation. Site-directed mutagenesis of bacterial cytochrome b; biochemical assays of ROS production and enzyme activity; structural analysis The Journal of biological chemistry High 21454570
2012 The Y268S mutation in P. falciparum CYTB (field isolate TM902CB) confers a 270-fold shift in atovaquone inhibitory constant (Ki), a ~40% reduction in Vmax of the bc1 complex, and a 3-fold increase in Km for decylubiquinol. Western blot analysis revealed reduced iron-sulfur protein (ISP) content in Y268S bc1, indicating weakened ISP-CYTB interaction. Gene expression analysis showed higher expression of bc1 and cytochrome c oxidase genes in the resistant strain, interpreted as compensation for reduced bc1 activity. Biochemical characterization of bc1 complex from atovaquone-resistant field isolate TM902CB; enzyme kinetics (Ki, Vmax, Km); Western blotting; gene expression analysis The Journal of biological chemistry High 22282497
2014 Direct biochemical evidence that atovaquone inhibits the cytochrome bc1 complex through CYTB mutations in P. berghei. Using isolated mitochondria from P. berghei atovaquone-resistant clones, dihydroorotate-cytochrome c reductase activity was tested across atovaquone concentrations. Resistant clones carrying Y268C or Y268N CYTB mutations showed ~100-fold higher IC50 compared to sensitive clones (1.5–40 nM vs. 0.132–0.465 nM), providing the first direct biochemical evidence linking specific CYTB mutations to atovaquone resistance in the intact parasite. Mitochondrial isolation from P. berghei; DHO-cytochrome c reductase activity assay across atovaquone concentration range; comparison of IC50 between resistant clones and sensitive controls Parasitology international High 25264100
2014 The reduction site (Qi site) of P. falciparum CYTB is a druggable antimalarial target. A novel macrocyclic inhibitor identified by diversity-oriented synthesis screening was shown by resistance selection and whole-genome sequencing to target the Qi site of CYTB. Combination of Qi site and Qo site inhibitors showed synergistic inhibition of P. falciparum. Whole-cell phenotypic screening; in vitro resistance selection; whole-genome sequencing; drug combination synergy assays The Journal of infectious diseases Medium 25336726
2018 Compounds CK-2-68 and RYL-552, reported as PfNDH2 inhibitors, unexpectedly selected mutations at the Qo pocket of P. falciparum CYTB (including Y268S, M133I, K272R) in resistance selection experiments, not in PfNDH2. Molecular docking showed all three ETC inhibitors (including atovaquone) bind to the Qo pocket of CYTB, with Y268 forming strong van der Waals interactions with atovaquone's hydroxynaphthoquinone ring but not with the quinolone rings of the other compounds. In vitro resistance selection; whole-genome sequencing; molecular docking to CYTB Qo pocket Proceedings of the National Academy of Sciences of the United States of America Medium 29844160
2023 WJM228, a 7-N-substituted-3-oxadiazole quinolone, targets the Qo site of P. falciparum CYTB. Forward genetic resistance studies revealed Qo site CYTB mutations confer resistance. In a biosensor assay, WJM228 was shown to impact the electron transport chain via inhibition of CYTB. The compound prevented pre-erythrocytic parasite and male gamete development and reduced asexual parasitemia in a P. berghei mouse model. Forward genetic resistance selection; whole-genome sequencing; mitochondrial biosensor assay; in vivo P. berghei mouse model ACS infectious diseases Medium 36853190
2024 PyAz90, a pyrimidine azepine compound, targets P. falciparum cytochrome b (CYTB) as a molecular target. P. falciparum-resistant parasites generated in vitro carried mutations in CYTB, and in vitro assays of mitochondrial activity confirmed inhibition of the bc1 complex. PyAz90 blocked parasite transmission to mosquitoes at nanomolar concentrations and inhibited asexual parasite multiplication. In vitro resistance selection; gene sequencing; mitochondrial activity assays; transmission-blocking assays JACS Au Medium 39483245
2025 Gamhépathiopine, a thienopyrimidinone, inhibits the Qo site of P. falciparum CYTB (complex III of the electron transport chain). In vitro evolution of resistance and whole genome analysis identified mutations within the Qo site of CYTB. Biochemical assays confirmed direct inhibition of complex III activity. Exogenous expression of S. cerevisiae DHODH (rendering the ETC dispensable) completely abrogated gamhépathiopine activity, confirming CYTB/ETC dependence. Cross-resistance profiling and docking studies indicated a similar but not identical binding pose to atovaquone. In vitro resistance evolution; whole genome sequencing; biochemical complex III assay; transgenic Plasmodium with yeast DHODH; cross-resistance profiling; molecular docking ACS infectious diseases High 40460517

Source papers

Stage 0 corpus · 79 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Mutations in Plasmodium falciparum cytochrome b that are associated with atovaquone resistance are located at a putative drug-binding site. Antimicrobial agents and chemotherapy 299 10898682
1997 Extrachromosomal DNA in the Apicomplexa. Microbiology and molecular biology reviews : MMBR 167 9106361
2010 African apes as reservoirs of Plasmodium falciparum and the origin and diversification of the Laverania subgenus. Proceedings of the National Academy of Sciences of the United States of America 117 20498054
2019 Exposing Anopheles mosquitoes to antimalarials blocks Plasmodium parasite transmission. Nature 109 30814727
2010 A molecular clock for malaria parasites. Science (New York, N.Y.) 102 20616281
2009 Towards high-throughput molecular detection of Plasmodium: new approaches and molecular markers. Malaria journal 100 19402894
1993 Structural features of Plasmodium cytochrome b that may underlie susceptibility to 8-aminoquinolines and hydroxynaphthoquinones. Molecular and biochemical parasitology 93 8459834
2007 Molecular basis of resistance to cytochrome bc1 inhibitors. FEMS yeast research 92 18093133
2003 Different mutation patterns of atovaquone resistance to Plasmodium falciparum in vitro and in vivo: rapid detection of codon 268 polymorphisms in the cytochrome b as potential in vivo resistance marker. Malaria journal 90 12665429
2006 Clinical atovaquone-proguanil resistance of Plasmodium falciparum associated with cytochrome b codon 268 mutations. Microbes and infection 84 16962361
1999 Mutations in the cytochrome b gene of Plasmodium berghei conferring resistance to atovaquone. Molecular and biochemical parasitology 82 10593174
2011 A chemical genomic analysis of decoquinate, a Plasmodium falciparum cytochrome b inhibitor. ACS chemical biology 76 21866942
2005 Uncovering the molecular mode of action of the antimalarial drug atovaquone using a bacterial system. The Journal of biological chemistry 76 15917236
2014 Direct evidence for the atovaquone action on the Plasmodium cytochrome bc1 complex. Parasitology international 74 25264100
2012 Cytochrome b mutation Y268S conferring atovaquone resistance phenotype in malaria parasite results in reduced parasite bc1 catalytic turnover and protein expression. The Journal of biological chemistry 74 22282497
2011 Improved performance with saliva and urine as alternative DNA sources for malaria diagnosis by mitochondrial DNA-based PCR assays. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 74 21595789
2006 The phylogeny of rodent malaria parasites: simultaneous analysis across three genomes. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 65 16765106
1989 Sequence identification of cytochrome b in Plasmodium gallinaceum. Molecular and cellular biology 57 2779560
2002 Mutations in cytochrome b resulting in atovaquone resistance are associated with loss of fitness in Plasmodium falciparum. Antimicrobial agents and chemotherapy 55 12121915
2009 Chimpanzee malaria parasites related to Plasmodium ovale in Africa. PloS one 52 19436742
2007 Modeling the molecular basis of atovaquone resistance in parasites and pathogenic fungi. Trends in parasitology 52 17826334
1993 Uniparental inheritance of the mitochondrial gene cytochrome b in Plasmodium falciparum. Current genetics 51 8467535
1994 Maternal inheritance of extrachromosomal DNA in malaria parasites. Molecular and biochemical parasitology 48 7935632
2018 Investigation of the seasonal microbiome of Anopheles coluzzii mosquitoes in Mali. PloS one 46 29596468
2008 Mutations in the Plasmodium falciparum cytochrome b gene are associated with delayed parasite recrudescence in malaria patients treated with atovaquone-proguanil. Malaria journal 44 19021900
2018 Targeted Structure-Activity Analysis of Endochin-like Quinolones Reveals Potent Qi and Qo Site Inhibitors of Toxoplasma gondii and Plasmodium falciparum Cytochrome bc1 and Identifies ELQ-400 as a Remarkably Effective Compound against Acute Experimental Toxoplasmosis. ACS infectious diseases 40 30117728
2003 Detection of atovaquone and Malarone resistance conferring mutations in Plasmodium falciparum cytochrome b gene (cytb). Molecular and cellular probes 40 12788029
2015 SYBR Green real-time PCR-RFLP assay targeting the plasmodium cytochrome B gene--a highly sensitive molecular tool for malaria parasite detection and species determination. PloS one 39 25774805
2015 Diversity of malaria parasites in great apes in Gabon. Malaria journal 38 25889049
2012 The evolutionary host switches of Polychromophilus: a multi-gene phylogeny of the bat malaria genus suggests a second invasion of mammals by a haemosporidian parasite. Malaria journal 38 22356874
2007 Parallel evolution of adaptive mutations in Plasmodium falciparum mitochondrial DNA during atovaquone-proguanil treatment. Molecular biology and evolution 35 17488741
2018 Clinical implications of Plasmodium resistance to atovaquone/proguanil: a systematic review and meta-analysis. The Journal of antimicrobial chemotherapy 34 29237012
2018 Selection of Plasmodium falciparum cytochrome B mutants by putative PfNDH2 inhibitors. Proceedings of the National Academy of Sciences of the United States of America 34 29844160
2011 Loss of a conserved tyrosine residue of cytochrome b induces reactive oxygen species production by cytochrome bc1. The Journal of biological chemistry 34 21454570
2005 Apparent absence of atovaquone/proguanil resistance in 477 Plasmodium falciparum isolates from untreated French travellers. The Journal of antimicrobial chemotherapy 34 16319183
2019 Assessment of malaria real-time PCR methods and application with focus on low-level parasitaemia. PloS one 33 31276473
2015 Molecular characterization of misidentified Plasmodium ovale imported cases in Singapore. Malaria journal 33 26577930
2018 Laboratory challenges of Plasmodium species identification in Aceh Province, Indonesia, a malaria elimination setting with newly discovered P. knowlesi. PLoS neglected tropical diseases 32 30500828
2014 The diminishing returns of atovaquone-proguanil for elimination of Plasmodium falciparum malaria: modelling mass drug administration and treatment. Malaria journal 32 25249272
2020 3D-QSAR, docking and ADMET properties of aurone analogues as antimalarial agents. Heliyon 31 32322700
2011 Design of anti-parasitic and anti-fungal hydroxy-naphthoquinones that are less susceptible to drug resistance. Molecular and biochemical parasitology 31 21251932
2014 Diversity-oriented synthesis probe targets Plasmodium falciparum cytochrome b ubiquinone reduction site and synergizes with oxidation site inhibitors. The Journal of infectious diseases 29 25336726
2011 Cytochrome b gene quantitative PCR for diagnosing Plasmodium falciparum infection in travelers. Journal of clinical microbiology 29 21508150
2007 Mutation underlying resistance of Plasmodium berghei to atovaquone in the quinone binding domain 2 (Qo(2)) of the cytochrome b gene. Parasitology international 29 18248769
2014 Novel Mutation in Cytochrome B of Plasmodium falciparum in One of Two Atovaquone-Proguanil Treatment Failures in Travelers Returning From Same Site in Nigeria. Open forum infectious diseases 28 25734129
2007 Molecular surveillance of drug-resistance associated mutations of Plasmodium falciparum in south-west Tanzania. Malaria journal 28 17224049
2020 Potent Tetrahydroquinolone Eliminates Apicomplexan Parasites. Frontiers in cellular and infection microbiology 27 32626661
2023 7-N-Substituted-3-oxadiazole Quinolones with Potent Antimalarial Activity Target the Cytochrome bc1 Complex. ACS infectious diseases 26 36853190
2022 Using an antimalarial in mosquitoes overcomes Anopheles and Plasmodium resistance to malaria control strategies. PLoS pathogens 26 35687594
2021 A citizen science-based survey of avian mortality focusing on haemosporidian infections in wild passerine birds. Malaria journal 26 34688278
2017 Avian malaria, ecological host traits and mosquito abundance in southeastern Amazonia. Parasitology 26 28345500
2013 Plasmodium (Novyella) nucleophilum from an Egyptian Goose in São Paulo Zoo, Brazil: microscopic confirmation and molecular characterization. International journal for parasitology. Parasites and wildlife 26 24533348
2001 Plasmodium falciparum: the effects of atovaquone resistance on respiration. Experimental parasitology 26 11560411
2014 Understanding the mechanism of atovaquone drug resistance in Plasmodium falciparum cytochrome b mutation Y268S using computational methods. PloS one 25 25334024
2009 Comparative gene evolution in haemosporidian (apicomplexa) parasites of birds and mammals. Molecular biology and evolution 25 19933837
2006 Prevalence of Plasmodium falciparum cytochrome b gene mutations in isolates imported from Africa, and implications for atovaquone resistance. Transactions of the Royal Society of Tropical Medicine and Hygiene 25 16690094
2006 [Antimalarial drug resistance]. Medecine et maladies infectieuses 25 16854546
2005 In vitro recrudescence of Plasmodium falciparum parasites suppressed to dormant state by atovaquone alone and in combination with proguanil. Transactions of the Royal Society of Tropical Medicine and Hygiene 24 15550263
2021 Chemoprotective antimalarials identified through quantitative high-throughput screening of Plasmodium blood and liver stage parasites. Scientific reports 22 33483532
2021 Targeted deep amplicon sequencing of antimalarial resistance markers in Plasmodium falciparum isolates from Cameroon. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases 22 33940188
2016 Plasmodium delichoni n. sp.: description, molecular characterisation and remarks on the exoerythrocytic merogony, persistence, vectors and transmission. Parasitology research 22 27000087
2025 In vivo screen of Plasmodium targets for mosquito-based malaria control. Nature 20 40399670
2024 Molecular prevalence, phylogeny and hematological impact of Toxoplasma gondii and Plasmodium spp. in common quails from Punjab, Pakistan. PloS one 12 38820542
2024 Pyrimidine Azepine Targets the Plasmodium bc 1 Complex and Displays Multistage Antimalarial Activity. JACS Au 9 39483245
2025 Hidden in plain sight: Morphological and molecular description of Plasmodium aramidis n. sp. in blood and tissues from Brazilian Wood Rails. Acta tropica 2 41072598
2025 A review on molecular markers of Plasmodium falciparum. Journal of parasitic diseases : official organ of the Indian Society for Parasitology 2 41230275
2026 Single-Cell Transcriptomics and Development of Gametocyte-Specific Molecular Markers for Avian Malaria Parasites. Molecular ecology resources 1 42409029
2025 Unraveling the host range of Plasmodium huffi: morphological, histopathological and molecular characterization in red-legged seriemas from Brazil. Parasitology 1 39865892
2025 Phylogenetic assessment of Plasmodium (Saurocytozoon) tupinambi comb. nov. (Haemosporida, Plasmodiidae) in golden tegu lizards: shedding light on a long-standing Haemosporida taxonomic puzzle. Parasitology 1 40152306
2025 Plasmodium species infecting lizards in the Brazilian Cerrado: Identification and description of a novel species, Plasmodium brasiliensis n. sp. PloS one 1 40173100
2025 The Prevalence and Genetic Diversity of Avian Malaria in Wild Birds in the Republic of Korea. Animals : an open access journal from MDPI 1 40218350
2025 The Thienopyrimidinone Gamhépathiopine Targets the QO Site of Plasmodium falciparum Cytochrome b. ACS infectious diseases 1 40460517
2025 Hidden Plasmodium diversity revealed in southeastern Asian passerines using next-generation amplicon sequencing. Current research in parasitology & vector-borne diseases 1 41049327
2026 Malaria outbreaks in Humboldt penguins and haemosporidian infections in avian hosts in zoos across Thailand. Current research in parasitology & vector-borne diseases 0 41626102
2026 Zoonotic and Anthroponotic Plasmodium spp. Circulation between Wild Primates and Indigenous Community, Peruvian Amazon, 2007-2020. Emerging infectious diseases 0 42116265
2026 A new Plasmodium Marchiafava & Celli, 1885 (Apicomplexa: Haemosporida) species in Cory's Shearwater (Calonectris borealis) [Cory]) (Aves: Procellariiformes) stranded in a coastal area in Brazil. Systematic parasitology 0 42142167
2025 Molecular Screening of Plasmodium spp. in Free-Living Ring-Tailed Coatis (Nasua nasua) and Nine-Banded Armadillos (Dasypus novemcinctus) in the Peruvian Amazon. Animals : an open access journal from MDPI 0 40867741
2025 Molecular detection of avian parasites in Australian mosquitoes (Culicidae). Journal of medical entomology 0 41055323
2025 Feeding Preferences of Mosquitoes (Culicidae) from the Eastern Balkans and Their Role in Transmission of Avian Malaria. Integrative zoology 0 41216928