{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T01:10:22Z","timestamp":1790298622884,"version":"4.1.0"},"reference-count":180,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T00:00:00Z","timestamp":1719187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["310030_214897"],"award-info":[{"award-number":["310030_214897"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Identification of drug targets and biochemical investigations on mechanisms of action are major issues in modern drug development. The present article is a critical review of the classical \u201cone drug\u201d\u2014\u201cone target\u201d paradigm. In fact, novel methods for target deconvolution and for investigation of resistant strains based on protein mass spectrometry have shown that multiple gene products and adaptation mechanisms are involved in the responses of pathogens to xenobiotics rather than one single gene or gene product. Resistance to drugs may be linked to differential expression of other proteins than those interacting with the drug in protein binding studies and result in complex cell physiological adaptation. Consequently, the unraveling of mechanisms of action needs approaches beyond proteomics. This review is focused on protozoan pathogens. The conclusions can, however, be extended to chemotherapies against other pathogens or cancer.<\/jats:p>","DOI":"10.3390\/ijms25136903","type":"journal-article","created":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T10:41:12Z","timestamp":1719225672000},"page":"6903","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Investigating Antiprotozoal Chemotherapies with Novel Proteomic Tools\u2014Chances and Limitations: A Critical Review"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8189-9270","authenticated-orcid":false,"given":"Joachim","family":"M\u00fcller","sequence":"first","affiliation":[{"name":"Institute of Parasitology, Vetsuisse Faculty, University of Bern, L\u00e4nggass-Strasse 122, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghalia","family":"Boubaker","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, Vetsuisse Faculty, University of Bern, L\u00e4nggass-Strasse 122, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, Vetsuisse Faculty, University of Bern, L\u00e4nggass-Strasse 122, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2820-0277","authenticated-orcid":false,"given":"Anne-Christine","family":"Uldry","sequence":"additional","affiliation":[{"name":"Proteomics and Mass Spectrometry Core Facility, Department for BioMedical Research (DBMR), University of Bern, L\u00e4nggass-Strasse 122, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Braga-Lagache","sequence":"additional","affiliation":[{"name":"Proteomics and Mass Spectrometry Core Facility, Department for BioMedical Research (DBMR), University of Bern, L\u00e4nggass-Strasse 122, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6364-7325","authenticated-orcid":false,"given":"Manfred","family":"Heller","sequence":"additional","affiliation":[{"name":"Proteomics and Mass Spectrometry Core Facility, Department for BioMedical Research (DBMR), University of Bern, L\u00e4nggass-Strasse 122, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0622-2128","authenticated-orcid":false,"given":"Andrew","family":"Hemphill","sequence":"additional","affiliation":[{"name":"Institute of Parasitology, Vetsuisse Faculty, University of Bern, L\u00e4nggass-Strasse 122, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1517\/14728222.6.4.517","article-title":"Target validation and drug discovery using genomic and protein-protein interaction technologies","volume":"6","author":"Pillutla","year":"2002","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ymben.2007.09.003","article-title":"A critique of the molecular target-based drug discovery paradigm based on principles of metabolic control: Advantages of pathway-based discovery","volume":"10","author":"Hellerstein","year":"2008","journal-title":"Metab. Eng."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1038\/nrd1202","article-title":"Target discovery","volume":"2","author":"Lindsay","year":"2003","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1093\/bib\/bbz122","article-title":"An omics perspective on drug target discovery platforms","volume":"21","author":"Paananen","year":"2020","journal-title":"Brief. Bioinform."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.cbpa.2019.10.008","article-title":"Targeted and proteome-wide analysis of metabolite-protein interactions","volume":"54","author":"Tsukidate","year":"2020","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.rvsc.2020.09.034","article-title":"Giardia duodenalis in humans and animals\u2014Transmission and disease","volume":"135","author":"Dixon","year":"2021","journal-title":"Res. Vet. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/s41579-021-00518-7","article-title":"Toxoplasma gondii infection and its implications within the central nervous system","volume":"19","author":"Matta","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1016\/j.ijpara.2021.08.007","article-title":"Taxonomy and molecular epidemiology of Cryptosporidium and Giardia\u2014A 50 year perspective (1971\u20132021)","volume":"51","author":"Ryan","year":"2021","journal-title":"Int. J. Parasitol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Marin-Garcia, P.J., Planas, N., and Llobat, L. (2022). Toxoplasma gondii in foods: Prevalence, control, and safety. Foods, 11.","DOI":"10.3390\/foods11162542"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Nayeri, T., Moosazadeh, M., Sarvi, S., and Daryani, A. (2022). Neospora caninum infection in aborting bovines and lost fetuses: A systematic review and meta-analysis. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0268903"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Reichel, M.P., Wahl, L.C., and Ellis, J.T. (2020). Research into Neospora caninum\u2014What Have We Learnt in the Last Thirty Years?. Pathogens, 9.","DOI":"10.3390\/pathogens9060505"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1016\/S0140-6736(05)66420-3","article-title":"Malaria","volume":"365","author":"Greenwood","year":"2005","journal-title":"Lancet"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1093\/bjps\/axy051","article-title":"Understanding the replication crisis as a base rate fallacy","volume":"72","author":"Bird","year":"2021","journal-title":"Br. J. Philos. Sci."},{"key":"ref_14","unstructured":"Edman, P. (1949). A method for the determination of amino acid sequence in peptides. Arch. Biochem., 22."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.jprot.2014.03.011","article-title":"Paleoproteomics explained to youngsters: How did the wedding of two-dimensional electrophoresis and protein sequencing spark proteomics on: Let there be light","volume":"107","author":"Rabilloud","year":"2014","journal-title":"J. Proteom."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2935","DOI":"10.1021\/ac00291a042","article-title":"Influence of the wavelength in high-irradiance ultraviolet-laser desorption mass-spectrometry of organic-molecules","volume":"57","author":"Karas","year":"1985","journal-title":"Anal. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3521","DOI":"10.1002\/rcm.5259","article-title":"Direct antigen detection from immunoprecipitated beads using matrix-assisted laser desorption\/ionization time-of-flight mass spectrometry; a new method for immunobeads-mass spectrometry (iMS)","volume":"25","author":"Shimada","year":"2011","journal-title":"Rapid Commun. Mass Spectrom."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"139155","DOI":"10.1016\/j.foodchem.2024.139155","article-title":"Discriminatory power of MALDI-TOF MS protein profiling analysis of pork meat and meat products","volume":"449","author":"Sedo","year":"2024","journal-title":"Food Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"120439","DOI":"10.1016\/j.talanta.2019.120439","article-title":"Protein profiling analysis based on matrix-assisted laser desorption\/ionization-Fourier transform ion cyclotron resonance mass spectrometry and its application in typing Streptomyces isolates","volume":"208","author":"Sun","year":"2020","journal-title":"Talanta"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Horisawa, S., and Iwamoto, K. (2022). Identification and typing of strains of wood-rotting basidiomycetes by protein profiling using MALDI-TOF MS. BioTech, 11.","DOI":"10.3390\/biotech11030030"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jmsacl.2021.09.001","article-title":"MALDI-ToF protein profiling as a potential rapid diagnostic platform for COVID-19","volume":"21","author":"Chivte","year":"2021","journal-title":"J. Mass Spectrom. Adv. Clin. Lab"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1021\/acs.analchem.3c03930","article-title":"Rapid profiling of the glycosylation effects on the binding of SARS-CoV-2 spike protein to angiotensin-converting enzyme 2 using MALDI-MS with high mass detection","volume":"96","author":"Zhou","year":"2024","journal-title":"Anal. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.cbpa.2018.10.023","article-title":"Protein identification strategies in MALDI imaging mass spectrometry: A brief review","volume":"48","author":"Ryan","year":"2019","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1006\/bbrc.1993.2009","article-title":"Protein identification by mass profile fingerprinting","volume":"195","author":"James","year":"1993","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1021\/pr101060v","article-title":"More than 100,000 detectable peptide species elute in single shotgun proteomics runs but the majority is inaccessible to data-dependent LC-MS\/MS","volume":"10","author":"Michalski","year":"2011","journal-title":"J. Proteome Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"O111.013698","DOI":"10.1074\/mcp.O111.013698","article-title":"Ultra high resolution linear ion trap Orbitrap mass spectrometer (Orbitrap Elite) facilitates top down LC MS\/MS and versatile peptide fragmentation modes","volume":"11","author":"Michalski","year":"2012","journal-title":"Mol. Cell Proteom."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.cels.2016.10.007","article-title":"Now, more than ever, proteomics needs better chromatography","volume":"3","author":"Shishkova","year":"2016","journal-title":"Cell Syst."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.copbio.2014.10.012","article-title":"Ion mobility-mass spectrometry strategies for untargeted systems, synthetic, and chemical biology","volume":"31","author":"May","year":"2015","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1021\/pr800538n","article-title":"Mass spectrometry based targeted protein quantification: Methods and applications","volume":"8","author":"Pan","year":"2009","journal-title":"J. Proteome Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1021\/acs.jproteome.2c00838","article-title":"An Introduction to mass spectrometry-based proteomics","volume":"22","author":"Shuken","year":"2023","journal-title":"J. Proteome Res."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Orsburn, B.C. (2024). Single cell proteomics by mass spectrometry reveals deep epigenetic insight and new targets of a class specific histone deacetylase inhibitor. bioRxiv.","DOI":"10.1101\/2024.01.05.574437"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1038\/s41592-021-01143-1","article-title":"The emerging landscape of single-molecule protein sequencing technologies","volume":"18","author":"Alfaro","year":"2021","journal-title":"Nat. Methods"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"eaax8978","DOI":"10.1126\/sciadv.aax8978","article-title":"Beyond mass spectrometry, the next step in proteomics","volume":"6","author":"Timp","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"16369","DOI":"10.1021\/acsnano.3c05628","article-title":"Engineering biological nanopore approaches toward protein sequencing","volume":"17","author":"Wei","year":"2023","journal-title":"ACS Nano"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2895","DOI":"10.1038\/s41467-023-38627-x","article-title":"MoS(2) nanopore identifies single amino acids with sub-1 Dalton resolution","volume":"14","author":"Wang","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1021\/cb5008794","article-title":"Quantitative proteomics of kinase inhibitor targets and mechanisms","volume":"10","author":"Daub","year":"2015","journal-title":"ACS Chem. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/978-1-4939-9744-2_10","article-title":"Phosphoproteomics profiling to identify altered signaling pathways and kinase-targeted cancer therapies","volume":"2051","author":"Deb","year":"2020","journal-title":"Methods Mol. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Hallal, M., Braga-Lagache, S., Jankovic, J., Simillion, C., Bruggmann, R., Uldry, A.C., Allam, R., Heller, M., and Bonadies, N. (2021). Inference of kinase-signaling networks in human myeloid cell line models by Phosphoproteomics using kinase activity enrichment analysis (KAEA). BMC Cancer, 21.","DOI":"10.1186\/s12885-021-08479-z"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1074\/mcp.TIR120.002048","article-title":"Fast quantitative analysis of timsTOF PASEF data with MSFragger and IonQuant","volume":"19","author":"Yu","year":"2020","journal-title":"Mol. Cell. Proteom."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1038\/nprot.2016.136","article-title":"The MaxQuant computational platform for mass spectrometry-based shotgun proteomics","volume":"11","author":"Tyanova","year":"2016","journal-title":"Nat. Protoc."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2394","DOI":"10.1074\/mcp.M114.046995","article-title":"A scalable approach for protein false discovery rate estimation in large proteomic data sets","volume":"14","author":"Savitski","year":"2015","journal-title":"Mol. Cell Proteom."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4539","DOI":"10.1038\/s41467-023-40129-9","article-title":"MSBooster: Improving peptide identification rates using deep learning-based features","volume":"14","author":"Yang","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3956","DOI":"10.1038\/s41467-024-48322-0","article-title":"Fragment ion intensity prediction improves the identification rate of non-tryptic peptides in timsTOF","volume":"15","author":"Adams","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3640","DOI":"10.1074\/mcp.M116.060491","article-title":"Robust label-free, quantitative profiling of circulating plasma microparticle (MP) associated proteins","volume":"15","author":"Buchs","year":"2016","journal-title":"Mol. Cell Proteom."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.euprot.2014.06.001","article-title":"Comparison of label-free quantification methods for the determination of protein complexes subunits stoichiometry","volume":"4","author":"Fabre","year":"2014","journal-title":"EuPA Open Proteom."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1021\/pr400897t","article-title":"A targeted in vivo SILAC approach for quantification of drug metabolism enzymes: Regulation by the constitutive androstane receptor","volume":"13","author":"Macleod","year":"2014","journal-title":"J. Proteome Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/978-1-61779-885-6_9","article-title":"Relative protein quantification by MS\/MS using the tandem mass tag technology","volume":"893","author":"Dayon","year":"2012","journal-title":"Methods Mol. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1021\/acs.jproteome.9b00701","article-title":"Systematic Comparison of Label-Free, SILAC, and TMT Techniques to Study Early Adaption toward Inhibition of EGFR Signaling in the Colorectal Cancer Cell Line DiFi","volume":"19","author":"Stepath","year":"2020","journal-title":"J. Proteome Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/nmeth.3901","article-title":"The Perseus computational platform for comprehensive analysis of (prote)omics data","volume":"13","author":"Tyanova","year":"2016","journal-title":"Nat. Methods"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Heller, M., Braga, S., M\u00fcller, N., and M\u00fcller, J. (2020). Transfection with plasmid causing stable expression of a foreign gene affects general proteome pattern in Giardia lamblia trophozoites. Front. Cell Infect. Microbiol., 10.","DOI":"10.3389\/fcimb.2020.602756"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Uldry, A.C., Maciel-Dominguez, A., Jornod, M., Buchs, N., Braga-Lagache, S., Brodard, J., Jankovic, J., Bonadies, N., and Heller, M. (2022). Effect of sample transportation on the proteome of human circulating blood extracellular vesicles. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23094515"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"103430","DOI":"10.1016\/j.drudis.2022.103430","article-title":"Profiling disease-selective drug targets: From proteomics to ligandomics","volume":"28","author":"Waduge","year":"2023","journal-title":"Drug Discov. Today"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/bs.mie.2020.06.002","article-title":"Ultrahigh throughput screening for enzyme function in droplets","volume":"643","author":"Neun","year":"2020","journal-title":"Methods Enzymol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e0065323","DOI":"10.1128\/jvi.00653-23","article-title":"A high-throughput screening assay for silencing established HIV-1 macrophage infection identifies nucleoside analogs that perturb H3K9me3 on proviral genomes","volume":"97","author":"Yi","year":"2023","journal-title":"J. Virol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1080\/13543776.2023.2178300","article-title":"New designs for HIV-1 integrase inhibitors: A patent review (2018-present)","volume":"33","author":"Taoda","year":"2023","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e20112","DOI":"10.1016\/j.heliyon.2023.e20112","article-title":"High throughput clone screening on overexpressed hERG1 and Kv1.3 potassium channels using ion channel reader (ICR) label free technology","volume":"9","author":"Montalbano","year":"2023","journal-title":"Heliyon"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.vascn.2004.04.001","article-title":"The [3H]dofetilide binding assay is a predictive screening tool for hERG blockade and proarrhythmia: Comparison of intact cell and membrane preparations and effects of altering [K+]o","volume":"50","author":"Diaz","year":"2004","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.toxlet.2024.02.004","article-title":"Screening for new ligands of the MB327-PAM-1 binding site of the nicotinic acetylcholine receptor","volume":"394","author":"Sichler","year":"2024","journal-title":"Toxicol. Lett."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.phrs.2016.11.012","article-title":"Artemisinin and its derivatives in treating protozoan infections beyond malaria","volume":"117","author":"Loo","year":"2017","journal-title":"Pharmacol. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1038\/nm.2471","article-title":"The discovery of artemisinin (qinghaosu) and gifts from Chinese medicine","volume":"17","author":"Tu","year":"2011","journal-title":"Nat. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1080\/14728222.2023.2217353","article-title":"Toxoplasma gondii infection: Novel emerging therapeutic targets","volume":"27","author":"Hemphill","year":"2023","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_62","first-page":"409","article-title":"Kinetics of protein aggregation. Quantitative estimation of the chaperone-like activity in test-systems based on suppression of protein aggregation","volume":"67","author":"Kurganov","year":"2002","journal-title":"Biochemistry"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"E31","DOI":"10.1208\/ps040431","article-title":"Quantitative comparison of functional screening by measuring intracellular Ca2+ with radioligand binding at recombinant human dopamine receptors","volume":"4","author":"Kassack","year":"2002","journal-title":"AAPS PharmSci"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0014-2999(02)02692-4","article-title":"Cloning, pharmacological characterization, and polymorphism screening of the guinea pig beta(2)-adrenoceptor","volume":"457","author":"Oostendorp","year":"2002","journal-title":"Eur. J. Pharmacol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e0023722","DOI":"10.1128\/aac.00237-22","article-title":"High-throughput screening platform to identify inhibitors of protein synthesis with potential for the treatment of malaria","volume":"66","author":"Tamaki","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1038\/nsmb.1818","article-title":"Toxoplasma gondii calcium-dependent protein kinase 1 is a target for selective kinase inhibitors","volume":"17","author":"Ojo","year":"2010","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2416","DOI":"10.1021\/jm201713h","article-title":"Development of Toxoplasma gondii calcium-dependent protein kinase 1 (TgCDPK1) inhibitors with potent anti-toxoplasma activity","volume":"55","author":"Johnson","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1021\/acschembio.1c00627","article-title":"Structural insight into effective inhibitors binding to Toxoplasma gondii dihydrofolate reductase thymidylate synthase","volume":"17","author":"Vanichtanankul","year":"2022","journal-title":"ACS Chem. Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.molbiopara.2007.07.009","article-title":"Antifolate screening using yeast expressing Plasmodium vivax dihydrofolate reductase and in vitro drug susceptibility assay for Plasmodium falciparum","volume":"156","author":"Djapa","year":"2007","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"23208","DOI":"10.1074\/jbc.M200455200","article-title":"The carboxyltransferase activity of the apicoplast acetyl-CoA carboxylase of Toxoplasma gondii is the target of aryloxyphenoxypropionate inhibitors","volume":"277","author":"Jelenska","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1186\/s13071-015-1268-5","article-title":"Characterization of Toxoplasma gondii glyoxalase 1 and evaluation of inhibitory effects of curcumin on the enzyme and parasite cultures","volume":"8","author":"Goo","year":"2015","journal-title":"Parasit. Vectors"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1016\/j.bbabio.2008.08.006","article-title":"The Toxoplasma gondii type-II NADH dehydrogenase TgNDH2-I is inhibited by 1-hydroxy-2-alkyl-4(1H)quinolones","volume":"1777","author":"Lin","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Harada, M., Nagai, J., Kurata, R., Shimizu, K., Cui, X., Isagawa, T., Semba, H., Ishihara, J., Yoshida, Y., and Takeda, N. (2020). Establishment of novel high-standard chemiluminescent assay for NTPase in two protozoans and its high-throughput screening. Mar. Drugs, 18.","DOI":"10.3390\/md18030161"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.exppara.2007.07.015","article-title":"Plasmodium falciparum: Functional mitochondrial ADP\/ATP transporter in Escherichia coli plasmic membrane as a tool for selective drug screening","volume":"118","author":"Razakantoanina","year":"2008","journal-title":"Exp. Parasitol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Walunj, S.B., Dias, M.M., Kaur, C., Wagstaff, K.M., Dey, V., Hick, C., Patankar, S., and Jans, D.A. (2022). High-throughput screening to identify inhibitors of Plasmodium falciparum importin alpha. Cells, 11.","DOI":"10.3390\/cells11071201"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1038\/s41467-022-28108-y","article-title":"Bicyclic azetidines target acute and chronic stages of Toxoplasma gondii by inhibiting parasite phenylalanyl t-RNA synthetase","volume":"13","author":"Radke","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1021\/acsinfecdis.9b00411","article-title":"Molecular target validation of aspartate transcarbamoylase from Plasmodium falciparum by Torin 2","volume":"6","author":"Bosch","year":"2020","journal-title":"ACS Infect. Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1080\/17460441.2020.1691996","article-title":"New directions in antimalarial target validation","volume":"15","author":"Batista","year":"2020","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/s41597-020-0377-y","article-title":"A chromosome-scale reference genome for Giardia intestinalis WB","volume":"7","author":"Xu","year":"2020","journal-title":"Sci. Data"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Kunz, S., Balmer, V., Sterk, G.J., Pollastri, M.P., Leurs, R., M\u00fcller, N., Hemphill, A., and Spycher, C. (2017). The single cyclic nucleotide-specific phosphodiesterase of the intestinal parasite Giardia lamblia represents a potential drug target. PLoS Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0005891"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1017\/S0031182020000657","article-title":"Comparative proteomics of three Giardia lamblia strains: Investigation of antigenic variation in the post-genomic era","volume":"147","author":"Braga","year":"2020","journal-title":"Parasitology"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.ijpddr.2022.05.004","article-title":"3-nitroimidazo [1,2-b]pyridazine as a novel scaffold for antiparasitics with sub-nanomolar anti-Giardia lamblia activity","volume":"19","author":"Zheng","year":"2022","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1017\/S0031182017002025","article-title":"A review on metronidazole: An old warhorse in antimicrobial chemotherapy","volume":"146","author":"Leitsch","year":"2017","journal-title":"Parasitology"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.1002\/med.21975","article-title":"Chemo-proteomics in antimalarial target identification and engagement","volume":"43","author":"Bailey","year":"2023","journal-title":"Med. Res. Rev."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Zhang, J., Li, M., Qiao, Y., Wang, W., Ma, L., and Liu, K. (2023). Target discovery of bioactive natural products with native-compound-coupled CNBr-activated Sepharose 4B beads (NCCB): Applications, mechanisms and outlooks. Bioorg. Med. Chem., 96.","DOI":"10.1016\/j.bmc.2023.117483"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1038\/s41589-022-01015-5","article-title":"Target deconvolution of HDAC pharmacopoeia reveals MBLAC2 as common off-target","volume":"18","author":"Lechner","year":"2022","journal-title":"Nat. Chem. Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/0014-5793(74)80993-2","article-title":"Spacer arms in affinity chromatography: Use of hydrophilic arms to control or eliminate nonbiospecific adsorption effects","volume":"43","author":"Barry","year":"1974","journal-title":"FEBS Lett."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1038\/254516a0","article-title":"Penicillin-binding proteins and cell shape in E","volume":"254","author":"Spratt","year":"1975","journal-title":"coli. Nature"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2999","DOI":"10.1073\/pnas.72.8.2999","article-title":"Distinct penicillin binding proteins involved in the division, elongation, and shape of Escherichia coli K12","volume":"72","author":"Spratt","year":"1975","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1128\/jb.145.1.398-403.1981","article-title":"Purification of penicillin-binding protein 2 of Escherichia coli","volume":"145","author":"Curtis","year":"1981","journal-title":"J. Bacteriol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/S1074-5521(00)00124-1","article-title":"Intracellular targets of cyclin-dependent kinase inhibitors: Identification by affinity chromatography using immobilised inhibitors","volume":"7","author":"Knockaert","year":"2000","journal-title":"Chem. Biol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1124\/mol.62.6.1364","article-title":"Discovery of novel targets of quinoline drugs in the human purine binding proteome","volume":"62","author":"Graves","year":"2002","journal-title":"Mol. Pharmacol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"5704","DOI":"10.1021\/pr3005315","article-title":"Plasmodium falciparum endoplasmic reticulum-resident calcium binding protein is a possible target of synthetic antimalarial endoperoxides, N-89 and N-251","volume":"11","author":"Morita","year":"2012","journal-title":"J. Proteome Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1979","DOI":"10.1128\/AAC.01548-06","article-title":"A novel Giardia lamblia nitroreductase, GlNR1, interacts with nitazoxanide and other thiazolides","volume":"51","author":"Wastling","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.ijpddr.2015.03.001","article-title":"Comparative characterisation of two nitroreductases from Giardia lamblia as potential activators of nitro compounds","volume":"5","author":"Rout","year":"2015","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"M\u00fcller, J., and M\u00fcller, N. (2019). Nitroreductases of bacterial origin in Giardia lamblia: Potential role in detoxification of xenobiotics. MicrobiologyOpen, 8.","DOI":"10.1002\/mbo3.904"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1002\/ijc.23755","article-title":"Thiazolides inhibit growth and induce glutathione-S-transferase Pi (GSTP1)-dependent cell death in human colon cancer cells","volume":"123","author":"Sidler","year":"2008","journal-title":"Int. J. Cancer"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"4095","DOI":"10.1038\/onc.2011.575","article-title":"Thiazolide-induced apoptosis in colorectal cancer cells is mediated via the Jun kinase-Bim axis and reveals glutathione-S-transferase P1 as Achilles\u2019 heel","volume":"31","author":"Sidler","year":"2012","journal-title":"Oncogene"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.exppara.2011.02.007","article-title":"Identification of a host cell target for the thiazolide class of broad-spectrum anti-parasitic drugs","volume":"128","author":"Hemphill","year":"2011","journal-title":"Exp. Parasitol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/AAC.01031-17","article-title":"Characterization of the activities of dinuclear thiolato-bridged arene ruthenium complexes against Toxoplasma gondii","volume":"61","author":"Basto","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Anghel, N., M\u00fcller, J., Serricchio, M., Jelk, J., Butikofer, P., Boubaker, G., Imhof, D., Ramseier, J., Desiatkina, O., and Paunescu, E. (2021). Cellular and molecular targets of nucleotide-tagged trithiolato-bridged arene ruthenium complexes in the protozoan parasites Toxoplasma gondii and Trypanosoma brucei. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910787"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"M\u00fcller, J., Boubaker, G., Imhof, D., Hanggeli, K., Haudenschild, N., Uldry, A.C., Braga-Lagache, S., Heller, M., Ortega-Mora, L.M., and Hemphill, A. (2022). Differential affinity chromatography coupled to mass spectrometry: A suitable tool to identify common binding proteins of a broad-range antimicrobial peptide derived from leucinostatin. Biomedicines, 10.","DOI":"10.3390\/biomedicines10112675"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"M\u00fcller, J., Anghel, N., Imhof, D., H\u00e4nggeli, K., Uldry, A.C., Braga-Lagache, S., Heller, M., Ojo, K.K., Ortega-Mora, L.M., and Van Voorhis, W.C. (2022). Common molecular targets of a quinoline based bumped kinase inhibitor in Neospora caninum and Danio rerio. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23042381"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Ajiboye, J., Uldry, A.C., Heller, M., Naguleswaran, A., Fan, E., Van Voorhis, W.C., Hemphill, A., and M\u00fcller, J. (2024). Molecular targets of the 5-amido-carboxamide bumped kinase inhibitor BKI-1748 in Cryptosporidium parvum and HCT-8 Host Cells. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25052707"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"10593","DOI":"10.1002\/anie.201304096","article-title":"Bioorthogonal approach to identify unsuspected drug targets in live cells","volume":"52","author":"Yang","year":"2013","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"14679","DOI":"10.1021\/acs.jafc.2c04972","article-title":"Activity-based proteomic identification of the S-thiolation targets of ajoene in MDA-MB-231 breast cancer cells","volume":"70","author":"Kusza","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"17187","DOI":"10.1021\/acs.analchem.3c01762","article-title":"Virus-like iron-gold heterogeneous nanoparticles for drug target screening","volume":"95","author":"Tang","year":"2023","journal-title":"Anal. Chem."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/bs.mie.2019.02.028","article-title":"Small molecule target identification using photo-affinity chromatography","volume":"622","author":"Seo","year":"2019","journal-title":"Methods Enzymol."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Penarete-Vargas, D.M., Boisson, A., Urbach, S., Chantelauze, H., Peyrottes, S., Fraisse, L., and Vial, H.J. (2014). A chemical proteomics approach for the search of pharmacological targets of the antimalarial clinical candidate albitiazolium in Plasmodium falciparum using photocrosslinking and click chemistry. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0113918"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.1073\/pnas.1600459113","article-title":"Artemisinin activity-based probes identify multiple molecular targets within the asexual stage of the malaria parasites Plasmodium falciparum 3D7","volume":"113","author":"Ismail","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1021\/acsinfecdis.7b00228","article-title":"Development of a photo-cross-linkable diaminoquinazoline inhibitor for target identification in Plasmodium falciparum","volume":"4","author":"Lubin","year":"2018","journal-title":"ACS Infect. Dis."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1039\/D3CB00109A","article-title":"Design, synthesis and modelling of photoreactive chemical probes for investigating target engagement of plasmepsin IX and X in Plasmodium falciparum","volume":"5","author":"Lisauskaite","year":"2024","journal-title":"RSC Chem. Biol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"e6","DOI":"10.1017\/erm.2024.6","article-title":"Stability-based approaches in chemoproteomics","volume":"26","author":"George","year":"2024","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.cell.2017.12.006","article-title":"A map of protein-metabolite interactions reveals principles of chemical communication","volume":"172","author":"Piazza","year":"2018","journal-title":"Cell"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"342755","DOI":"10.1016\/j.aca.2024.342755","article-title":"Thermostability-assisted limited proteolysis-coupled mass spectrometry for capturing drug target proteins and sites","volume":"1312","author":"Yang","year":"2024","journal-title":"Anal. Chim. Acta"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/978-1-4939-0354-2_20","article-title":"Ligand screening using fluorescence thermal shift analysis (FTS)","volume":"1140","author":"Luan","year":"2014","journal-title":"Struct. Genom. Drug Discov. Methods Protoc."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.1038\/nprot.2014.138","article-title":"The cellular thermal shift assay for evaluating drug target interactions in cells","volume":"9","author":"Jafari","year":"2014","journal-title":"Nat. Protoc."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1126\/science.1233606","article-title":"Monitoring drug target engagement in cells and tissues using the cellular thermal shift assay","volume":"341","author":"Molina","year":"2013","journal-title":"Science"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/bs.mie.2022.07.018","article-title":"Two-dimensional electrophoresis-cellular thermal shift assay (2DE-CETSA) for target identification of bioactive compounds","volume":"675","author":"Muroi","year":"2022","journal-title":"Methods Enzymol."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Friman, T. (2020). Mass spectrometry-based cellular thermal shift assay (CETSA(R)) for target deconvolution in phenotypic drug discovery. Bioorg. Med. Chem., 28.","DOI":"10.1016\/j.bmc.2019.115174"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/978-1-0716-3457-8_5","article-title":"Thermal proteome profiling for drug target identification and probing of protein states","volume":"2718","author":"Sauer","year":"2023","journal-title":"Methods Mol. Biol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"2629","DOI":"10.1021\/acs.jproteome.3c00111","article-title":"Comparison of quantitative mass spectrometric methods for drug target identification by thermal proteome profiling","volume":"22","author":"George","year":"2023","journal-title":"J. Proteome Res."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"e9673","DOI":"10.1002\/rcm.9673","article-title":"Identifying drug targets with thermal proteome profiling using IBT-16plex","volume":"38","author":"Shi","year":"2024","journal-title":"Rapid Commun. Mass Spectrom."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1255784","DOI":"10.1126\/science.1255784","article-title":"Tracking cancer drugs in living cells by thermal profiling of the proteome","volume":"346","author":"Savitski","year":"2014","journal-title":"Science"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Ball, K.A., Webb, K.J., Coleman, S.J., Cozzolino, K.A., Jacobsen, J., Jones, K.R., Stowell, M.H.B., and Old, W.M. (2020). An isothermal shift assay for proteome scale drug-target identification. Commun. Biol., 3.","DOI":"10.1038\/s42003-020-0795-6"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Zijlmans, D.W., Hernandez-Quiles, M., Jansen, P., Becher, I., Stein, F., Savitski, M.M., and Vermeulen, M. (2023). STPP-UP: An alternative method for drug target identification using protein thermal stability. J. Biol. Chem., 299.","DOI":"10.1016\/j.jbc.2023.105279"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1038\/s41592-020-01022-1","article-title":"Cell surface thermal proteome profiling tracks perturbations and drug targets on the plasma membrane","volume":"18","author":"Kalxdorf","year":"2021","journal-title":"Nat. Methods"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/978-1-0716-2624-5_4","article-title":"Solvent-induced protein precipitation for drug target discovery","volume":"2554","author":"Zhang","year":"2023","journal-title":"Methods Mol. Biol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/j.chembiol.2021.02.008","article-title":"Multiple unbiased approaches identify oxidosqualene cyclase as the molecular target of a promising anti-leishmanial","volume":"28","author":"Paradela","year":"2021","journal-title":"Cell Chem. Biol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"100704","DOI":"10.1016\/j.xpro.2021.100704","article-title":"Utilizing thermal proteome profiling to identify the molecular targets of anti-leishmanial compounds","volume":"2","author":"Wyllie","year":"2021","journal-title":"STAR Protoc."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Ibarra-Meneses, A.V., Corbeil, A., Wagner, V., Beaudry, F., do Monte-Neto, R.L., and Fernandez-Prada, C. (2022). Exploring direct and indirect targets of current antileishmanial drugs using a novel thermal proteomics profiling approach. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.954144"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1038\/s41596-020-0310-z","article-title":"Cellular thermal shift assay for the identification of drug-target interactions in the Plasmodium falciparum proteome","volume":"15","author":"Dziekan","year":"2020","journal-title":"Nat. Protoc."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1021\/acschembio.0c00369","article-title":"Identifying the target of an antiparasitic compound in Toxoplasma using thermal proteome profiling","volume":"15","author":"Herneisen","year":"2020","journal-title":"ACS Chem. Biol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1016\/j.cell.2018.03.053","article-title":"Pervasive protein thermal stability variation during the cell cycle","volume":"173","author":"Becher","year":"2018","journal-title":"Cell"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1080\/17460441.2023.2276349","article-title":"In vitro screening technologies for the discovery and development of novel drugs against Toxoplasma gondii","volume":"19","author":"Hemphill","year":"2024","journal-title":"Expert. Opin. Drug Discov."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Tjorve, K.M.C., and Tjorve, E. (2017). The use of Gompertz models in growth analyses, and new Gompertz-model approach: An addition to the Unified-Richards family. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0178691"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1038\/nrmicro.2016.34","article-title":"Distinguishing between resistance, tolerance and persistence to antibiotic treatment","volume":"14","author":"Brauner","year":"2016","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.ijpddr.2018.04.008","article-title":"Physiological aspects of nitro drug resistance in Giardia lamblia","volume":"8","author":"Hemphill","year":"2018","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_139","first-page":"1","article-title":"Proteomic characterization of Toxoplasma gondii ME49 derived strains resistant to the artemisinin derivatives artemiside and artemisone implies potential mode of action independent of ROS formation","volume":"21","author":"Schlange","year":"2022","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/j.pt.2020.05.013","article-title":"\u2018Artemisinin Resistance\u2019: Something New or Old? Something of a Misnomer?","volume":"36","author":"Wellems","year":"2020","journal-title":"Trends Parasitol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"105725","DOI":"10.1016\/j.isci.2022.105725","article-title":"Ring-stage growth arrest: Metabolic basis of artemisinin tolerance in Plasmodium falciparum","volume":"26","author":"Yu","year":"2023","journal-title":"iScience"},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Winzer, P., Anghel, N., Imhof, D., Balmer, V., Ortega-Mora, L.M., Ojo, K.K., Van Voorhis, W.C., M\u00fcller, J., and Hemphill, A. (2020). Neospora caninum: Structure and Fate of Multinucleated Complexes Induced by the Bumped Kinase Inhibitor BKI-1294. Pathogens, 9.","DOI":"10.3390\/pathogens9050382"},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Winzer, P., M\u00fcller, J., Imhof, D., Ritler, D., Uldry, A.C., Braga-Lagache, S., Heller, M., Ojo, K.K., Van Voorhis, W.C., and Ortega-Mora, L.M. (2020). Neospora caninum: Differential Proteome of Multinucleated Complexes Induced by the Bumped Kinase Inhibitor BKI-1294. Microorganisms, 8.","DOI":"10.3390\/microorganisms8060801"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1128\/EC.00092-12","article-title":"Plasmid vectors for proteomic analyses in Giardia: Purification of virulence factors and analysis of the proteasome","volume":"11","author":"Stadelmann","year":"2012","journal-title":"Eukaryot. Cell"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.mib.2007.07.006","article-title":"Molecular genetic tools in Toxoplasma and Plasmodium: Achievements and future needs","volume":"10","author":"Meissner","year":"2007","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1098\/rstb.2001.1009","article-title":"Technologies for the study of gene and protein expression in Plasmodium","volume":"357","author":"Carucci","year":"2002","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"11703","DOI":"10.1073\/pnas.90.24.11703","article-title":"Stable molecular transformation of Toxoplasma gondii: A selectable dihydrofolate reductase-thymidylate synthase marker based on drug-resistance mutations in malaria","volume":"90","author":"Donald","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1006\/meth.1997.0505","article-title":"Development of molecular genetics for Neospora caninum: A complementary system to Toxoplasma gondii","volume":"13","author":"Howe","year":"1997","journal-title":"Methods"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1111\/j.1462-5822.2004.00399.x","article-title":"RNA interference in protozoan parasites","volume":"6","author":"Ullu","year":"2004","journal-title":"Cell Microbiol."},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Sidik, S.M., Hackett, C.G., Tran, F., Westwood, N.J., and Lourido, S. (2014). Efficient genome engineering of Toxoplasma gondii using CRISPR\/Cas9. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0100450"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/mBio.01114-14","article-title":"Efficient gene disruption in diverse strains of Toxoplasma gondii using CRISPR\/CAS9","volume":"5","author":"Shen","year":"2014","journal-title":"MBio"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1016\/j.cell.2016.08.019","article-title":"A Genome-wide CRISPR screen in Toxoplasma Identifies essential apicomplexan genes","volume":"166","author":"Sidik","year":"2016","journal-title":"Cell"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/s41579-023-00926-x","article-title":"Plasmids, a molecular cornerstone of antimicrobial resistance in the One Health era","volume":"22","author":"Top","year":"2024","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.pt.2018.04.007","article-title":"Redox pathways as drug targets in microaerophilic parasites","volume":"34","author":"Leitsch","year":"2018","journal-title":"Trends Parasitol."},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"M\u00fcller, J., Heller, M., Uldry, A.C., Braga, S., and M\u00fcller, N. (2021). Nitroreductase activites in Giardia lamblia: ORF 17150 encodes a quinone reductase with nitroreductase activity. Pathogens, 10.","DOI":"10.3390\/pathogens10020129"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"4296","DOI":"10.1038\/ncomms5296","article-title":"Opposing effects of target overexpression reveal drug mechanisms","volume":"5","author":"Palmer","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Hanggeli, K.P.A., Hemphill, A., M\u00fcller, N., Heller, M., Uldry, A.C., Braga-Lagache, S., M\u00fcller, J., and Boubaker, G. (2023). Comparative proteomic analysis of Toxoplasma gondii RH wild-type and four SRS29B (SAG1) knock-out clones reveals significant differences between individual strains. Int. J. Mol. Sci., 24.","DOI":"10.20944\/preprints202305.1482.v1"},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Freisleben, F., Behrmann, L., Thaden, V., Muschhammer, J., Bokemeyer, C., Fiedler, W., and Wellbrock, J. (2020). Downregulation of GLI3 expression mediates chemotherapy resistance in acute myeloid leukemia. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21145084"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1042\/ETLS20170113","article-title":"Drug resistance in protozoan parasites","volume":"1","year":"2017","journal-title":"Emerg. Top. Life Sci."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/nature01097","article-title":"Genome sequence of the human malaria parasite Plasmodium falciparum","volume":"419","author":"Gardner","year":"2002","journal-title":"Nature"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"41","DOI":"10.2174\/1568005043480989","article-title":"Proteomic approaches to studying drug targets and resistance in Plasmodium","volume":"4","author":"Cooper","year":"2004","journal-title":"Curr. Drug Targets Infect. Disord."},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Wang, S., Huang, F., Yan, H., Yin, J., and Xia, Z. (2023). A review of malaria molecular markers for drug resistance in Plasmodium falciparum and Plasmodium vivax in China. Front. Cell Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1167220"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.pt.2023.09.011","article-title":"The many paths to artemisinin resistance in Plasmodium falciparum","volume":"39","author":"Pandit","year":"2023","journal-title":"Trends Parasitol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.pt.2023.11.007","article-title":"Plasmodium falciparum ring-stage plasticity and drug resistance","volume":"40","author":"Platon","year":"2024","journal-title":"Trends Parasitol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1093\/jac\/dkn142","article-title":"Identification of differentially expressed genes in a Giardia lamblia WB C6 clone resistant to nitazoxanide and metronidazole","volume":"62","author":"Ley","year":"2008","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/0035-9203(92)90095-T","article-title":"Induction of metronidazole and furazolidone resistance in Giardia","volume":"86","author":"Townson","year":"1992","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1093\/jac\/dkm205","article-title":"Characterization of Giardia lamblia WB C6 clones resistant to nitazoxanide and to metronidazole","volume":"60","author":"Sterk","year":"2007","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S0020-7519(97)00172-0","article-title":"Anaerobic bacterial metabolism in the ancient eukaryote Giardia duodenalis","volume":"28","author":"Brown","year":"1998","journal-title":"Int. J. Parasitol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.ijpddr.2019.03.002","article-title":"Resistance formation to nitro drugs in Giardia lamblia: No common markers identified by comparative proteomics","volume":"9","author":"Braga","year":"2019","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"Ansell, B.R., Baker, L., Emery, S.J., McConville, M.J., Svard, S.G., Gasser, R.B., and Jex, A.R. (2017). Transcriptomics indicates active and passive metronidazole resistance mechanisms in three seminal Giardia lines. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.00398"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"giy024","DOI":"10.1093\/gigascience\/giy024","article-title":"Differential protein expression and post-translational modifications in metronidazole-resistant Giardia duodenalis","volume":"7","author":"Emery","year":"2018","journal-title":"Gigascience"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1002\/pmic.200600552","article-title":"SELDI-TOF-MS analysis of chloroquine resistant and sensitive Plasmodium falciparum strains","volume":"7","author":"Koncarevic","year":"2007","journal-title":"Proteomics"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.ijpddr.2012.12.002","article-title":"Identification of differentially expressed proteins in sulfadiazine resistant and sensitive strains of Toxoplasma gondii using difference-gel electrophoresis (DIGE)","volume":"3","author":"Doliwa","year":"2013","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/AAC.00051-18","article-title":"Toxoplasma calcium-dependent protein kinase 1 inhibitors: Probing activity and resistance using cellular thermal shift assays","volume":"62","author":"Scheele","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_175","doi-asserted-by":"crossref","unstructured":"Burata, O.E., Yeh, T.J., Macdonald, C.B., and Stockbridge, R.B. (2022). Still rocking in the structural era: A molecular overview of the small multidrug resistance (SMR) transporter family. J. Biol. Chem., 298.","DOI":"10.1016\/j.jbc.2022.102482"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"230","DOI":"10.15698\/mic2016.05.503","article-title":"Chemical proteomics approach reveals the direct targets and the heme-dependent activation mechanism of artemisinin in Plasmodium falciparum using an artemisinin-based activity probe","volume":"3","author":"Wang","year":"2016","journal-title":"Microb. Cell"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.molimm.2022.05.118","article-title":"How to get away with murder: The multiple strategies employed by pathogenic protozoa to avoid complement killing","volume":"149","author":"Horta","year":"2022","journal-title":"Mol. Immunol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1111\/j.1462-5822.2009.01367.x","article-title":"Antigenic variation in Giardia lamblia","volume":"11","author":"Prucca","year":"2009","journal-title":"Cell Microbiol."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1016\/S0020-7519(98)00137-4","article-title":"Antigenic variation and the murine immune response to Giardia lamblia","volume":"28","author":"Gottstein","year":"1998","journal-title":"Int. J. Parasitol."},{"key":"ref_180","doi-asserted-by":"crossref","unstructured":"M\u00fcller, J., Vermathen, M., Leitsch, D., Vermathen, P., and M\u00fcller, N. (2020). Metabolomic profiling of wildtype and transgenic Giardia lamblia Strains by (1)H HR-MAS NMR Spectroscopy. Metabolites, 10.","DOI":"10.3390\/metabo10020053"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/13\/6903\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:03:27Z","timestamp":1760108607000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/13\/6903"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,24]]},"references-count":180,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["ijms25136903"],"URL":"https:\/\/doi.org\/10.3390\/ijms25136903","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,24]]}}}