{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T09:16:53Z","timestamp":1772529413390,"version":"3.50.1"},"reference-count":121,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Free-living amoebae of the <jats:italic>Naegleria<\/jats:italic> genus belong to the major protist clade Heterolobosea and are ubiquitously distributed in soil and freshwater habitats. Of the 47 <jats:italic>Naegleria<\/jats:italic> species described, <jats:italic>N. fowleri<\/jats:italic> is the only one being pathogenic to humans, causing a rare but fulminant primary amoebic meningoencephalitis. Some <jats:italic>Naegleria<\/jats:italic> genome sequences are publicly available, but the genetic basis for <jats:italic>Naegleria<\/jats:italic> diversity and ability to thrive in diverse environments (including human brain) remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Herein, we constructed a high-quality <jats:italic>Naegleria<\/jats:italic> genus pangenome to obtain a comprehensive catalog of genes encoded by these amoebae. For this, we first sequenced, assembled, and annotated six new <jats:italic>Naegleria<\/jats:italic> genomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and Discussion<\/jats:title><jats:p>Genome architecture analyses revealed that <jats:italic>Naegleria<\/jats:italic> may use genome plasticity features such as ploidy\/aneuploidy to modulate their behavior in different environments. When comparing 14 near-to-complete genome sequences, our results estimated the theoretical <jats:italic>Naegleria<\/jats:italic> pangenome as a closed genome, with 13,943 genes, including 3,563 core and 10,380 accessory genes. The functional annotations revealed that a large fraction of <jats:italic>Naegleria<\/jats:italic> genes show significant sequence similarity with those already described in other kingdoms, namely Animalia and Plantae. Comparative analyses highlighted a remarkable genomic heterogeneity, even for closely related strains and demonstrate that <jats:italic>Naegleria<\/jats:italic> harbors extensive genome variability, reflected in different metabolic repertoires. If <jats:italic>Naegleria<\/jats:italic> core genome was enriched in conserved genes essential for metabolic, regulatory and survival processes, the accessory genome revealed the presence of genes involved in stress response, macromolecule modifications, cell signaling and immune response. Commonly reported <jats:italic>N. fowleri<\/jats:italic> virulence-associated genes were present in both core and accessory genomes, suggesting that <jats:italic>N. fowleri<\/jats:italic>\u2019s ability to infect human brain could be related to its unique species-specific genes (mostly of unknown function) and\/or to differential gene expression. The construction of <jats:italic>Naegleria<\/jats:italic> first pangenome allowed us to move away from a single reference genome (that does not necessarily represent each species as a whole) and to identify essential and dispensable genes in <jats:italic>Naegleria<\/jats:italic> evolution, diversity and biology, paving the way for further genomic and post-genomic studies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2022.1056418","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T04:50:00Z","timestamp":1675227000000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Naegleria genus pangenome reveals new structural and functional insights into the versatility of these free-living amoebae"],"prefix":"10.3389","volume":"13","author":[{"given":"Alexis","family":"Dereeper","sequence":"first","affiliation":[]},{"given":"Nina","family":"Allouch","sequence":"additional","affiliation":[]},{"given":"Vincent","family":"Guerlais","sequence":"additional","affiliation":[]},{"given":"Ma\u00eblle","family":"Garnier","sequence":"additional","affiliation":[]},{"given":"Laurence","family":"Ma","sequence":"additional","affiliation":[]},{"given":"Johan F.","family":"De Jonckheere","sequence":"additional","affiliation":[]},{"given":"Sandeep J.","family":"Joseph","sequence":"additional","affiliation":[]},{"given":"Ibne Karim M.","family":"Ali","sequence":"additional","affiliation":[]},{"given":"Antoine","family":"Talarmin","sequence":"additional","affiliation":[]},{"given":"Isabel","family":"Marcelino","sequence":"additional","affiliation":[]}],"member":"1965","published-online":{"date-parts":[[2023,2,1]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/0304-4165(80)90096-3","article-title":"Adenylate cyclase activity during growth and encystment of Acanthamoeba castellanii","volume":"629","author":"Achar","year":"1980","journal-title":"Biochim. Biophys. Acta \u2013 Gen. Subj."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1486","DOI":"10.3389\/fmicb.2018.01486","article-title":"A large open pangenome and a small core genome for giant pandoraviruses","volume":"9","author":"Aherfi","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"e01034","DOI":"10.1128\/MRA.01034-20","article-title":"Draft chromosome sequences of a clinical isolate of the free-living ameba Naegleria fowleri","volume":"10","author":"Ali","year":"2021","journal-title":"Microbiol. Resour. Announc."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1186\/s13059-019-1829-6","article-title":"RaGOO: fast and accurate reference-guided scaffolding of draft genomes","volume":"20","author":"Alonge","year":"2019","journal-title":"Genome Biol."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"e0007759","DOI":"10.1371\/journal.pntd.0007759","article-title":"Adaptive iron utilization compensates for the lack of an inducible uptake system in Naegleria fowleri and represents a potential target for therapeutic intervention","volume":"14","author":"Arbon","year":"2020","journal-title":"PLoS Negl. Trop. Dis."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1128\/jb.128.1.56-68.1976","article-title":"Thermal adaptation in yeast: growth temperatures, membrane lipid, and cytochrome composition of psychrophilic, mesophilic, and thermophilic yeasts","volume":"128","author":"Arthur","year":"1976","journal-title":"J. Bacteriol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1021\/acschemneuro.6b00197","article-title":"Primary amoebic meningoencephalitis: Neurochemotaxis and neurotropic preferences of Naegleria fowleri","volume":"7","author":"Baig","year":"2016","journal-title":"ACS Chem. Neurosci."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1111\/j.1550-7408.1985.tb03063.x","article-title":"Chemotaxis by Entamoeba histolytica1","volume":"32","author":"Bailey","year":"1985","journal-title":"J. Protozool."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1038\/s41477-020-0733-0","article-title":"Plant pan-genomes are the new reference","volume":"6","author":"Bayer","year":"2020","journal-title":"Nat. Plants"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1002\/msb.201304521","article-title":"Evolution and functional cross-talk of protein post-translational modifications","volume":"9","author":"Beltrao","year":"2013","journal-title":"Mol. Syst. Biol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"a019604","DOI":"10.1101\/cshperspect.a019604","article-title":"Rapid mechanisms for generating genome diversity: whole ploidy shifts, aneuploidy, and loss of heterozygosity","volume":"4","author":"Bennett","year":"2014","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"4104","DOI":"10.1038\/s41467-022-31832-0","article-title":"A time-resolved multi-omics atlas of Acanthamoeba castellanii encystment","volume":"13","author":"Bernard","year":"2022","journal-title":"Nat. Commun."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"110","DOI":"10.3389\/fcimb.2012.00110","article-title":"Lateral gene exchanges shape the genomes of amoeba-resisting microorganisms","volume":"2","author":"Bertelli","year":"2012","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1016\/j.celrep.2018.09.055","article-title":"Lipids are the preferred substrate of the Protist Naegleria gruberi, relative of a human brain pathogen","volume":"25","author":"Bexkens","year":"2018","journal-title":"Cell Rep."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"e04940","DOI":"10.7554\/eLife.04940","article-title":"Neurofibromin controls macropinocytosis and phagocytosis in Dictyostelium","volume":"4","author":"Bloomfield","year":"2015","journal-title":"eLife"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"e4958","DOI":"10.7717\/peerj.4958","article-title":"D-GENIES: dot plot large genomes in an interactive, efficient and simple way","volume":"6","author":"Cabanettes","year":"2018","journal-title":"PeerJ"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1093\/genetics\/115.2.265","article-title":"First evidence for Diploidy and genetic recombination in free-living amoebae of the genus Naegleria on the basis of electrophoretic variation","volume":"115","author":"Cariou","year":"1987","journal-title":"Genetics"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"41724","DOI":"10.1074\/jbc.M110.156380","article-title":"Functional dissection of adenylate cyclase R, an inducer of spore encapsulation","volume":"285","author":"Chen","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1126\/science.1143991","article-title":"Immune-like phagocyte activity in the social amoeba","volume":"317","author":"Chen","year":"2007","journal-title":"Science"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"R11","DOI":"10.1186\/gb-2013-14-2-r11","article-title":"Genome of Acanthamoeba castellanii highlights extensive lateral gene transfer and early evolution of tyrosine kinase signaling","volume":"14","author":"Clarke","year":"2013","journal-title":"Genome Biol."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1111\/j.1550-7408.1986.tb05547.x","article-title":"Movement of Naegleria fowleri stimulated by mammalian cells in vitro 1","volume":"33","author":"Cline","year":"1986","journal-title":"J. Protozool."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1111\/j.1550-7408.1983.tb02936.x","article-title":"Comparison of Naegleria fowleri and Naegleria gruberi cultivated in the same nutrient medium","volume":"30","author":"Cline","year":"1983","journal-title":"J. Protozool."},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1093\/bioadv\/vbac010","article-title":"KaruBioNet: a network and discussion group for a better collaboration and structuring of bioinformatics in Guadeloupe (French West Indies)","volume":"2","author":"Couvin","year":"2022","journal-title":"Bioinforma. Adv."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"giab008","DOI":"10.1093\/gigascience\/giab008","article-title":"Twelve years of SAMtools and BCFtools","volume":"10","author":"Danecek","year":"2021","journal-title":"Gigascience"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1128\/aem.33.4.751-757.1977","article-title":"Use of an axenic medium for differentiation between pathogenic and nonpathogenic Naegleria fowleri isolates","volume":"33","author":"De Jonckheere","year":"1977","journal-title":"Appl. Environ. Microbiol."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1007\/BF00931073","article-title":"Variation of electrophoretic karyotypes among Naegleria spp","volume":"76","author":"De Jonckheere","year":"1989","journal-title":"Parasitol. Res."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/S1434-4610(98)70030-6","article-title":"Sequence variation in the ribosomal internal transcribed spacers, including the 5.8S rDNA, of Naegleria spp","volume":"149","author":"De Jonckheere","year":"1998","journal-title":"Protist"},{"key":"ref28","first-page":"309","article-title":"A century of research on the amoeboflagellate genus Naegleria","volume":"41","author":"De Jonckheere","year":"2002","journal-title":"Acta Protozool."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1520","DOI":"10.1016\/j.meegid.2011.07.023","article-title":"Origin and evolution of the worldwide distributed pathogenic amoeboflagellate Naegleria fowleri","volume":"11","author":"De Jonckheere","year":"2011","journal-title":"Infect. Genet. Evol."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"S2","DOI":"10.1016\/j.exppara.2014.07.011","article-title":"What do we know by now about the genus Naegleria?","volume":"145","author":"De Jonckheere","year":"2014","journal-title":"Exp. Parasitol."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1080\/14787210.2021.1882302","article-title":"Drug discovery for primary amebic meningoencephalitis: from screen to identification of leads","volume":"19","author":"Debnath","year":"2021","journal-title":"Expert Rev. Anti-Infect. Ther."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"W295","DOI":"10.1093\/nar\/gkv351","article-title":"SNiPlay3: a web-based application for exploration and large scale analyses of genomic variations","volume":"43","author":"Dereeper","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1021\/acs.jproteome.8b00702","article-title":"Cytoscape StringApp: network analysis and visualization of proteomics data","volume":"18","author":"Doncheva","year":"2019","journal-title":"J. Proteome Res."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"1906","DOI":"10.3389\/fimmu.2017.01906","article-title":"Eat prey, live: Dictyostelium discoideum as a model for cell-autonomous defenses","volume":"8","author":"Dunn","year":"2018","journal-title":"Front. Immunol."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1186\/gb-2008-9-6-225","article-title":"What makes pathogens pathogenic","volume":"9","author":"Ehrlich","year":"2008","journal-title":"Genome Biol."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1038\/nature03481","article-title":"The genome of the social amoeba Dictyostelium discoideum","volume":"435","author":"Eichinger","year":"2005","journal-title":"Nature"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1186\/s13059-019-1832-y","article-title":"OrthoFinder: phylogenetic orthology inference for comparative genomics","volume":"20","author":"Emms","year":"2019","journal-title":"Genome Biol."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"9451","DOI":"10.1073\/pnas.1921046117","article-title":"RepeatModeler2 for automated genomic discovery of transposable element families","volume":"117","author":"Flynn","year":"2020","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1016\/j.resmic.2011.03.003","article-title":"The Naegleria genome: a free-living microbial eukaryote lends unique insights into core eukaryotic cell biology","volume":"162","author":"Fritz-Laylin","year":"2011","journal-title":"Res. Microbiol."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1016\/j.cell.2010.01.032","article-title":"The genome of Naegleria gruberi illuminates early eukaryotic versatility","volume":"140","author":"Fritz-Laylin","year":"2010","journal-title":"Cells"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1111\/evo.13205","article-title":"Ploidy tug-of-war: evolutionary and genetic environments influence the rate of ploidy drive in a human fungal pathogen","volume":"71","author":"Gerstein","year":"2017","journal-title":"Evolution"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1083\/jcb.200109001","article-title":"Phosphoinositides and phagocytosis","volume":"155","author":"Gillooly","year":"2001","journal-title":"J. Cell Biol."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.tig.2019.11.006","article-title":"Pangenomics comes of age: from bacteria to plant and animal applications","volume":"36","author":"Golicz","year":"2020","journal-title":"Trends Genet."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1038\/nbt.1883","article-title":"Full-length transcriptome assembly from RNA-Seq data without a reference genome","volume":"29","author":"Grabherr","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.ijpddr.2020.10.001","article-title":"Copper detoxification machinery of the brain-eating amoeba Naegleria fowleri involves copper-translocating ATPase and the antioxidant system","volume":"14","author":"Grechnikova","year":"2020","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"759532","DOI":"10.3389\/fncel.2021.759532","article-title":"Dictyostelium discoideum as a model for investigating neurodegenerative diseases","volume":"15","author":"Haver","year":"2021","journal-title":"Front. Cell. Neurosci."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1186\/s12915-021-01078-1","article-title":"Genomics and transcriptomics yields a system-level view of the biology of the pathogen Naegleria fowleri","volume":"19","author":"Herman","year":"2021","journal-title":"BMC Biol."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"W123","DOI":"10.1093\/nar\/gkt418","article-title":"WebAUGUSTUS\u2013a web service for training AUGUSTUS and predicting genes in eukaryotes","volume":"41","author":"Hoff","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"3118","DOI":"10.1093\/gbe\/evy241","article-title":"Comparative genomics supports sex and meiosis in diverse Amoebozoa","volume":"10","author":"Hofstatter","year":"2018","journal-title":"Genome Biol. Evol."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1186\/1471-2105-12-491","article-title":"MAKER2: an annotation pipeline and genome-database management tool for second-generation genome projects","volume":"12","author":"Holt","year":"2011","journal-title":"BMC Bioinformatics"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1111\/1440-1681.13192","article-title":"Naegleria fowleri: sources of infection, pathophysiology, diagnosis, and management; a review","volume":"47","author":"Jahangeer","year":"2020","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1099\/mic.0.055020-0","article-title":"Pathogenic Naegleria fowleri and non-pathogenic Naegleria lovaniensis exhibit differential adhesion to, and invasion of, extracellular matrix proteins","volume":"158","author":"Jamerson","year":"2012","journal-title":"Microbiology"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1093\/bioinformatics\/btu031","article-title":"InterProScan 5: genome-scale protein function classification","volume":"30","author":"Jones","year":"2014","journal-title":"Bioinformatics"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"e00637","DOI":"10.1128\/mSphere.00637-21","article-title":"Comparative genomic and transcriptomic analysis of naegleria fowleri clinical and environmental isolates","volume":"6","author":"Joseph","year":"2021","journal-title":"mSphere"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1016\/s0168-9525(00)02093-x","article-title":"Repbase update: a database and an electronic journal of repetitive elements","volume":"16","author":"Jurka","year":"2000","journal-title":"Trends Genet."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1186\/s12864-020-07167-9","article-title":"Near-chromosome level genome assembly reveals ploidy diversity and plasticity in the intestinal protozoan parasite Entamoeba histolytica","volume":"21","author":"Kawano-Sugaya","year":"2020","journal-title":"BMC Genomics"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1038\/nrg2386","article-title":"Horizontal gene transfer in eukaryotic evolution","volume":"9","author":"Keeling","year":"2008","journal-title":"Nat. Rev. Genet."},{"key":"ref001","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1093\/cid\/cir961","article-title":"Fatal Naegleria fowleri infection acquired in minnesota: Possible expanded range of a deadly thermophilic organism","volume":"54","author":"Kemble","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/14787210.2021.1927712","article-title":"Brain-eating amoebae: is killing the parasite our only option to prevent death?","volume":"20","author":"Khan","year":"2021","journal-title":"Expert Rev. Anti-Infect. Ther."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"1733","DOI":"10.4103\/1673-5374.217353","article-title":"Brain-derived neurotropic factor and GABAergic transmission in neurodegeneration and neuroregeneration","volume":"12","author":"Kim","year":"2017","journal-title":"Neural Regen. Res."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"827435","DOI":"10.3389\/fphys.2022.827435","article-title":"The cellular and developmental roles of Cullins, Neddylation, and the COP9 signalosome in Dictyostelium discoideum","volume":"13","author":"Kim","year":"2022","journal-title":"Front. Physiol."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1101\/gr.129684.111","article-title":"VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing","volume":"22","author":"Koboldt","year":"2012","journal-title":"Genome Res."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/1471-2105-5-59","article-title":"Gene finding in novel genomes","volume":"5","author":"Korf","year":"2004","journal-title":"BMC Bioinformatics"},{"key":"ref63","doi-asserted-by":"publisher","first-page":"1639","DOI":"10.1101\/gr.092759.109","article-title":"Circos: an information aesthetic for comparative genomics","volume":"19","author":"Krzywinski","year":"2009","journal-title":"Genome Res."},{"key":"ref64","doi-asserted-by":"publisher","first-page":"388","DOI":"10.3390\/pathogens10040388","article-title":"A novel cysteine protease inhibitor of Naegleria fowleri that is specifically expressed during encystation and at mature cysts","volume":"10","author":"L\u00ea","year":"2021","journal-title":"Pathogens"},{"key":"ref65","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1128\/EC.05238-11","article-title":"Posttranslational modifications of proteins in the pathobiology of medically relevant fungi","volume":"11","author":"Leach","year":"2012","journal-title":"Eukaryot. Cell"},{"key":"ref66","doi-asserted-by":"publisher","first-page":"W293","DOI":"10.1093\/nar\/gkab301","article-title":"Interactive tree of life (iTOL) v5: an online tool for phylogenetic tree display and annotation","volume":"49","author":"Letunic","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref67","author":"Li","year":"2013"},{"key":"ref68","doi-asserted-by":"publisher","first-page":"3094","DOI":"10.1093\/bioinformatics\/bty191","article-title":"Minimap2: pairwise alignment for nucleotide sequences","volume":"34","author":"Li","year":"2018","journal-title":"Bioinformatics"},{"key":"ref69","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1186\/s12864-018-4994-1","article-title":"The genome of Naegleria lovaniensis, the basis for a comparative approach to unravel pathogenicity factors of the human pathogenic amoeba N. fowleri","volume":"19","author":"Liechti","year":"2018","journal-title":"BMC Genomics"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"16040","DOI":"10.1038\/s41598-019-52572-0","article-title":"Nanopore sequencing improves the draft genome of the human pathogenic amoeba Naegleria fowleri","volume":"9","author":"Liechti","year":"2019","journal-title":"Sci. Rep."},{"key":"ref71","doi-asserted-by":"publisher","first-page":"419","DOI":"10.3389\/fmicb.2015.00419","article-title":"Whole-genome comparative analysis of virulence genes unveils similarities and differences between endophytes and other symbiotic bacteria","volume":"6","author":"L\u00f2pez-Fern\u00e0ndez","year":"2015","journal-title":"Front. Microbiol."},{"key":"ref002","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.pt.2019.10.008","article-title":"Is Naegleria fowleri an Emerging Parasite","volume":"36","author":"Maciver","year":"2020","journal-title":"Trends Parasitol."},{"key":"ref72","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1128\/MMBR.64.3.461-488.2000","article-title":"Thermophilic fungi: their physiology and enzymes","volume":"64","author":"Maheshwari","year":"2000","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref73","doi-asserted-by":"publisher","first-page":"2492","DOI":"10.1093\/gbe\/evz171","article-title":"Intraspecific variation in Protists: clues for microevolution from Poteriospumella lacustris (Chrysophyceae)","volume":"11","author":"Majda","year":"2019","journal-title":"Genome Biol. Evol."},{"key":"ref74","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1111\/j.1550-7408.1987.tb03147.x","article-title":"Chemotaxis by Naegleria fowleri for bacteria","volume":"34","author":"Marciano-Cabral","year":"1987","journal-title":"J. Protozool."},{"key":"ref75","doi-asserted-by":"crossref","DOI":"10.14806\/ej.17.1.200","article-title":"Cutadapt removes adapter sequences from high-throughput sequencing reads","volume":"17","author":"Martin","year":"2011","journal-title":"EMBnet. J."},{"key":"ref76","doi-asserted-by":"publisher","first-page":"781","DOI":"10.2217\/fmb-2016-0230","article-title":"Nf-GH, a glycosidase secreted by Naegleria fowleri, causes mucin degradation: an in vitro and in vivo study","volume":"12","author":"Mart\u00ednez-Castillo","year":"2017","journal-title":"Future Microbiol."},{"key":"ref77","doi-asserted-by":"publisher","first-page":"e000243","DOI":"10.1099\/mgen.0.000243","article-title":"Pan-genome analyses of model fungal species","volume":"5","author":"McCarthy","year":"2019","journal-title":"Microb. Genomics"},{"key":"ref78","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1080\/15548627.2016.1226737","article-title":"Autophagy in Dictyostelium: mechanisms, regulation and disease in a simple biomedical model","volume":"13","author":"Mesquita","year":"2017","journal-title":"Autophagy"},{"key":"ref79","doi-asserted-by":"publisher","first-page":"1302","DOI":"10.1093\/molbev\/mst029","article-title":"Expression divergence between Escherichia coli and salmonella enterica serovar typhimurium reflects their lifestyles","volume":"30","author":"Meysman","year":"2013","journal-title":"Mol. Biol. Evol."},{"key":"ref80","doi-asserted-by":"publisher","first-page":"e02410","DOI":"10.1128\/AAC.02410-18","article-title":"Enzymatic and structural characterization of the Naegleria fowleri Glucokinase","volume":"63","author":"Milanes","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref81","doi-asserted-by":"publisher","first-page":"e1003854","DOI":"10.1371\/journal.pgen.1003854","article-title":"Xbp1 directs global repression of budding yeast transcription during the transition to quiescence and is important for the longevity and reversibility of the quiescent state","volume":"9","author":"Miles","year":"2013","journal-title":"PLoS Genet."},{"key":"ref82","doi-asserted-by":"publisher","first-page":"e1008406","DOI":"10.1371\/journal.ppat.1008406","article-title":"Battling brain-eating amoeba: enigmas surrounding immunity to Naegleria fowleri","volume":"16","author":"Moseman","year":"2020","journal-title":"PLoS Pathog."},{"key":"ref83","doi-asserted-by":"publisher","first-page":"e54414","DOI":"10.1371\/journal.pone.0054414","article-title":"Survey of Naegleria fowleri in geothermal recreational waters of Guadeloupe (French West Indies)","volume":"8","author":"Moussa","year":"2013","journal-title":"PLoS One"},{"key":"ref84","doi-asserted-by":"publisher","first-page":"409","DOI":"10.3390\/pathogens9050409","article-title":"An optimized Most probable number (MPN) Method to assess the number of thermophilic free-living amoebae (FLA) in water samples","volume":"9","author":"Moussa","year":"2020","journal-title":"Pathogens"},{"key":"ref85","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1007\/s00425-021-03567-7","article-title":"Detection of ploidy and chromosomal aberrations in commercial oil palm using high-throughput SNP markers","volume":"253","author":"Ngoot-Chin","year":"2021","journal-title":"Planta"},{"key":"ref86","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1007\/s13149-009-0028-1","article-title":"Diagnostic mol\u00e9culaire d\u2019une m\u00e9ningoenc\u00e9phalite amibienne primitive \u00e0 l\u2019occasion d\u2019un cas fatal en Guadeloupe","volume":"103","author":"Nicolas","year":"2010","journal-title":"Bull. la Soci\u00e9t\u00e9 Pathol. Exot."},{"key":"ref87","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1039\/b502002f","article-title":"Photoactivated adenylyl cyclase (PAC) genes in the flagellate Euglena gracilis mutant strains","volume":"4","author":"Ntefidou","year":"2005","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref88","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1016\/j.ijpara.2011.04.004","article-title":"Naegleria gruberi metabolism","volume":"41","author":"Opperdoes","year":"2011","journal-title":"Int. J. Parasitol."},{"key":"ref89","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1111\/j.1550-7408.2000.tb00020.x","article-title":"Analysis of the 5.8S rRNA gene and the internal transcribed spacers in Naegleria spp. and in N. fowleri","volume":"47","author":"Pelandakis","year":"2000","journal-title":"J. Eukaryot. Microbiol."},{"key":"ref90","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1038\/hdy.1992.26","article-title":"Genetic structure of natural populations of the free-living amoeba, Naegleria lovaniensis. Evidence for sexual reproduction","volume":"68","author":"Pernin","year":"1992","journal-title":"Heredity (Edinb)."},{"key":"ref91","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1038\/s41586-018-0030-5","article-title":"Genome evolution across 1,011 Saccharomyces cerevisiae isolates","volume":"556","author":"Peter","year":"2018","journal-title":"Nature"},{"key":"ref92","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1002\/wsbm.1185","article-title":"Post-translational modification: nature\u2019s escape from genetic imprisonment and the basis for dynamic information encoding","volume":"4","author":"Prabakaran","year":"2012","journal-title":"WIREs Syst. Biol. Med."},{"key":"ref93","doi-asserted-by":"publisher","first-page":"e102","DOI":"10.1002\/cpbi.102","article-title":"Using SPAdes De Novo Assembler","volume":"70","author":"Prjibelski","year":"2020","journal-title":"Curr. Protoc. Bioinforma."},{"key":"ref94","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1051\/parasite\/2021033","article-title":"Application of the omics sciences to the study of Naegleria fowleri, Acanthamoeba spp., and Balamuthia mandrillaris: current status and future projections","volume":"28","author":"Rodriguez-Anaya","year":"2021","journal-title":"Parasite"},{"key":"ref95","doi-asserted-by":"publisher","first-page":"321","DOI":"10.3390\/pathogens9050321","article-title":"Encystment induces Down-regulation of an acetyltransferase-like gene in Acanthamoeba castellanii","volume":"9","author":"Rolland","year":"2020","journal-title":"Pathogens"},{"key":"ref96","doi-asserted-by":"publisher","first-page":"936","DOI":"10.2174\/138945011795677845","article-title":"Acanthamoeba-bacteria: a model to study host interaction with human pathogens","volume":"12","author":"Sandstr\u00f6m","year":"2011","journal-title":"Curr. Drug Targets"},{"key":"ref97","doi-asserted-by":"publisher","first-page":"1479","DOI":"10.1091\/mbc.e03-08-0622","article-title":"Adenylyl cyclase G is activated by an intramolecular Osmosensor","volume":"15","author":"Saran","year":"2004","journal-title":"Mol. Biol. Cell"},{"key":"ref98","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1016\/j.pt.2021.10.004","article-title":"Three encephalitis-causing amoebae and their distinct interactions with the host","volume":"38","author":"Sarink","year":"2022","journal-title":"Trends Parasitol."},{"key":"ref99","doi-asserted-by":"publisher","first-page":"9792","DOI":"10.1038\/s41598-020-66429-4","article-title":"Sex in Symbiodiniaceae dinoflagellates: genomic evidence for independent loss of the canonical synaptonemal complex","volume":"10","author":"Shah","year":"2020","journal-title":"Sci. Rep."},{"key":"ref100","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1016\/j.pt.2020.07.014","article-title":"Lateral gene transfer mechanisms and Pan-genomes in eukaryotes","volume":"36","author":"Sibbald","year":"2020","journal-title":"Trends Parasitol."},{"key":"ref101","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/j.actatropica.2016.09.009","article-title":"Biology and pathogenesis of Naegleria fowleri","volume":"164","author":"Siddiqui","year":"2016","journal-title":"Acta Trop."},{"key":"ref102","doi-asserted-by":"publisher","first-page":"3210","DOI":"10.1093\/bioinformatics\/btv351","article-title":"BUSCO: assessing genome assembly and annotation completeness with single-copy orthologs","volume":"31","author":"Sim\u00e3o","year":"2015","journal-title":"Bioinformatics"},{"key":"ref103","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/s12859-015-0517-0","article-title":"Micropan: an R-package for microbial pan-genomics","volume":"16","author":"Snipen","year":"2015","journal-title":"BMC Bioinformatics"},{"key":"ref104","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1007\/s00436-010-1760-y","article-title":"The Nf-actin gene is an important factor for food-cup formation and cytotoxicity of pathogenic Naegleria fowleri","volume":"106","author":"Sohn","year":"2010","journal-title":"Parasitol. Res."},{"key":"ref105","doi-asserted-by":"publisher","first-page":"8.13.1","DOI":"10.1002\/0471250953.bi0813s47","article-title":"Biological network exploration with Cytoscape 3","volume":"47","author":"Su","year":"2014","journal-title":"Curr. Protoc. Bioinforma."},{"key":"ref106","doi-asserted-by":"publisher","first-page":"61","DOI":"10.3389\/fcimb.2018.00061","article-title":"Acanthamoeba and Dictyostelium as cellular models for legionella infection","volume":"8","author":"Swart","year":"2018","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref107","doi-asserted-by":"publisher","first-page":"D607","DOI":"10.1093\/nar\/gky1131","article-title":"STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets","volume":"47","author":"Szklarczyk","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref108","doi-asserted-by":"publisher","first-page":"4.10.1-4.10.14","DOI":"10.1002\/0471250953.bi0410s25","article-title":"Using RepeatMasker to identify repetitive elements in genomic sequences","volume":"25","author":"Tarailo-Graovac","year":"2009","journal-title":"Curr. Protoc. Bioinforma"},{"key":"ref109","doi-asserted-by":"publisher","first-page":"9841","DOI":"10.1038\/s41598-022-14131-y","article-title":"The draft genome of Cochliopodium minus reveals a complete meiosis toolkit and provides insight into the evolution of sexual mechanisms in Amoebozoa","volume":"12","author":"Tekle","year":"2022","journal-title":"Sci. Rep."},{"key":"ref110","doi-asserted-by":"publisher","first-page":"evx002","DOI":"10.1093\/gbe\/evx002","article-title":"Amoebozoans are secretly but ancestrally sexual: evidence for sex genes and potential novel crossover pathways in diverse groups of amoebae","volume":"9","author":"Tekle","year":"2017","journal-title":"Genome Biol. Evol."},{"key":"ref111","doi-asserted-by":"publisher","first-page":"13950","DOI":"10.1073\/pnas.0506758102","article-title":"Genome analysis of multiple pathogenic isolates of Streptococcus agalactiae: implications for the microbial pan-genome","volume":"102","author":"Tettelin","year":"2005","journal-title":"Proc. Natl. Acad. Sci."},{"key":"ref112","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/j.patbio.2012.03.002","article-title":"Pathogenic free-living amoebae: epidemiology and clinical review","volume":"60","author":"Trabelsi","year":"2012","journal-title":"Pathol. Biol."},{"key":"ref113","doi-asserted-by":"publisher","first-page":"5606","DOI":"10.1038\/s41467-019-13568-6","article-title":"Responses of unicellular predators to cope with the phototoxicity of photosynthetic prey","volume":"10","author":"Uzuka","year":"2019","journal-title":"Nat. Commun."},{"key":"ref114","doi-asserted-by":"publisher","first-page":"e202007158","DOI":"10.1083\/jcb.202007158","article-title":"Conserved actin machinery drives microtubule-independent motility and phagocytosis in Naegleria","volume":"219","author":"Velle","year":"2020","journal-title":"J. Cell Biol."},{"key":"ref115","doi-asserted-by":"publisher","first-page":"e178","DOI":"10.1093\/nar\/gkq622","article-title":"MapSplice: accurate mapping of RNA-seq reads for splice junction discovery","volume":"38","author":"Wang","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref116","doi-asserted-by":"publisher","first-page":"724940","DOI":"10.3389\/fcell.2021.724940","article-title":"How phagocytes acquired the capability of hunting and removing pathogens from a human body: lessons learned from chemotaxis and phagocytosis of Dictyostelium discoideum (review)","volume":"9","author":"Xu","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref117","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1016\/j.bbrc.2015.10.090","article-title":"UDP-glucose pyrophosphorylase Ugp1 is involved in oxidative stress response and long-term survival during stationary phase in Saccharomyces cerevisiae","volume":"467","author":"Yi","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref118","doi-asserted-by":"publisher","first-page":"2240","DOI":"10.1093\/molbev\/msab020","article-title":"The Mastigamoeba balamuthi genome and the nature of the free-living ancestor of Entamoeba","volume":"38","author":"\u017d\u00e1rsk\u00fd","year":"2021","journal-title":"Mol. Biol. Evol."},{"key":"ref119","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1186\/1471-2164-15-496","article-title":"Genome-wide identification of pathogenicity factors of the free-living amoeba Naegleria fowleri","volume":"15","author":"Zysset-Burri","year":"2014","journal-title":"BMC Genomics"}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2022.1056418\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T04:50:06Z","timestamp":1675227006000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2022.1056418\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,1]]},"references-count":121,"alternative-id":["10.3389\/fmicb.2022.1056418"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2022.1056418","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,1]]},"article-number":"1056418"}}