{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:59:32Z","timestamp":1791331172397,"version":"4.3.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013851","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000}}],"reference-count":73,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100023448","name":"Robert Koch-Institute","doi-asserted-by":"crossref","award":["internal grants"],"award-info":[{"award-number":["internal grants"]}],"id":[{"id":"10.13039\/501100023448","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["GRK2046 Research Training Programme"],"award-info":[{"award-number":["GRK2046 Research Training Programme"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["Priority Programme SPP 2332"],"award-info":[{"award-number":["Priority Programme SPP 2332"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["549511580"],"award-info":[{"award-number":["549511580"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH\/NIAID","award":["R21AI178544"],"award-info":[{"award-number":["R21AI178544"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Arginine metabolism plays a key role in the energy metabolism of the intestinal parasite\n                    <jats:italic>Giardia duodenalis<\/jats:italic>\n                    , an amitochondrial protozoan that infects humans and animals and causes significant morbidity. Despite that an arginine deiminase (ADI) has been implicated in virulence\n                    <jats:italic>,<\/jats:italic>\n                    it remains unknown if ADI allele variants from the different genetic\n                    <jats:italic>G. duodenalis<\/jats:italic>\n                    subgroups (assemblages) differ in function. Here, the hypothesis was tested that sequence variation detected between\n                    <jats:italic>G. duodenalis<\/jats:italic>\n                    ADI alleles from the two\n                    <jats:italic>G. duodenalis<\/jats:italic>\n                    assemblage types found in humans affects functional parameters of the enzyme with potential consequences in life cycle progression. The ADI enzyme\u2019s affinity for arginine was\u2009~\u20095fold reduced in sub-assemblage AII isolates, a human specific assemblage, in comparison to zoonotic sub-assemblage AI and B isolates. We identified the two amino acid residues responsible for the lower substrate affinity of ADI\n                    <jats:sub>AII<\/jats:sub>\n                    variant. By combining genetic ADI-knockout mutants, biochemical assays of substrate affinity, and cellular analyses of life-cycle progression, we demonstrate that ADI is required for efficient parasite encystation and that the lower substrate affinity in ADI\n                    <jats:sub>AII<\/jats:sub>\n                    correlates with reduced encystation efficiency. We further demonstrate that arginine is required for efficient encystation, and use an ADI knockout strain to confirm that ADI mediates this arginine dependence. Thus, we suggest that ADI is a quantitative trait that affects life cycle progression of\n                    <jats:italic>G. duodenalis<\/jats:italic>\n                    with putative clinical and epidemiological relevance.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013851","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T18:38:44Z","timestamp":1767897524000},"page":"e1013851","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Arginine metabolism has a pivotal function for the encystation of Giardia duodenalis"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2609-9654","authenticated-orcid":true,"given":"Christian","family":"Klotz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricarda","family":"Leisering","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kari D.","family":"Hagen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah N.","family":"Starcevich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Ewald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"T\u00fcrken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malte","family":"Marquardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia","family":"Schramm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Totta","family":"Ehret Kasemo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Marek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Seeber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Ignatius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott C.","family":"Dawson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toni","family":"Aebischer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"key":"ppat.1013851.ref001","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.meegid.2017.12.001","article-title":"Host specificity in the Giardia duodenalis 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