{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T02:03:34Z","timestamp":1776909814236,"version":"3.51.2"},"reference-count":56,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,7,16]],"date-time":"2014-07-16T00:00:00Z","timestamp":1405468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI096836"],"award-info":[{"award-number":["AI096836"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI063263"],"award-info":[{"award-number":["AI063263"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The vacuolar proton pyrophosphatase (<jats:styled-content style=\"fixed-case\">H<\/jats:styled-content><jats:sup>+<\/jats:sup>\u2010<jats:styled-content style=\"fixed-case\">PP<\/jats:styled-content>ase) of <jats:styled-content style=\"fixed-case\"><jats:italic>T<\/jats:italic><\/jats:styled-content><jats:italic>oxoplasma gondii<\/jats:italic> (<jats:styled-content style=\"fixed-case\">TgVP<\/jats:styled-content>1), a membrane proton pump, localizes to acidocalcisomes and a novel lysosome\u2010like compartment termed plant\u2010like vacuole (<jats:styled-content style=\"fixed-case\">PLV<\/jats:styled-content>) or vacuolar compartment (<jats:styled-content style=\"fixed-case\">VAC<\/jats:styled-content>). We report the characterization of a <jats:styled-content style=\"fixed-case\"><jats:italic>T<\/jats:italic><\/jats:styled-content><jats:italic>. gondii null<\/jats:italic> mutant for the <jats:styled-content style=\"fixed-case\"><jats:italic>TgVP1<\/jats:italic><\/jats:styled-content> gene. Propagation of these mutants decreased significantly because of deficient attachment and invasion of host cells, which correlated with deficient microneme secretion. Processing of cathepsin <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">CPL<\/jats:styled-content>) in these mutants was deficient only when the parasites were incubated in the presence of low concentrations of the vacuolar <jats:styled-content style=\"fixed-case\">H<\/jats:styled-content><jats:sup>+<\/jats:sup>\u2010<jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>ase (<jats:styled-content style=\"fixed-case\">V<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">H<\/jats:styled-content><jats:sup>+<\/jats:sup>\u2010<jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>ase) inhibitor bafilomycin <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content><jats:sub>1<\/jats:sub>, suggesting that either <jats:styled-content style=\"fixed-case\">TgVP<\/jats:styled-content>1 or the <jats:styled-content style=\"fixed-case\"><jats:italic>T<\/jats:italic><\/jats:styled-content><jats:italic>. gondii<\/jats:italic>\u2005<jats:styled-content style=\"fixed-case\">V<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">H<\/jats:styled-content><jats:sup>+<\/jats:sup>\u2010<jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>ase (<jats:styled-content style=\"fixed-case\">TgVATP<\/jats:styled-content>ase) are sufficient to support <jats:styled-content style=\"fixed-case\">CPL<\/jats:styled-content> processing. The lack of <jats:styled-content style=\"fixed-case\">TgVP<\/jats:styled-content>1 did not affect processing of micronemal proteins, indicating that it does not contribute to pro<jats:styled-content style=\"fixed-case\">MIC<\/jats:styled-content> maturations. The <jats:styled-content style=\"fixed-case\"><jats:italic>TgVP1<\/jats:italic><\/jats:styled-content>\u2005<jats:italic>null<\/jats:italic> mutants were more sensitive to extracellular conditions and were less virulent in mice. We demonstrate that <jats:styled-content style=\"fixed-case\"><jats:italic>T<\/jats:italic><\/jats:styled-content><jats:italic>. gondii<\/jats:italic> tachyzoites possess regulatory volume decrease capability during hypo\u2010osmotic stress and this ability is impaired in <jats:styled-content style=\"fixed-case\"><jats:italic>TgVP1<\/jats:italic><\/jats:styled-content>\u2005<jats:italic>null<\/jats:italic> mutants implicating <jats:styled-content style=\"fixed-case\">TgVP<\/jats:styled-content>1 in osmoregulation. We hypothesize that osmoregulation is needed for host cell invasion and that <jats:styled-content style=\"fixed-case\">TgVP<\/jats:styled-content>1 plays a role during the normal lytic cycle of <jats:styled-content style=\"fixed-case\"><jats:italic>T<\/jats:italic><\/jats:styled-content><jats:italic>. gondii<\/jats:italic>.<\/jats:p>","DOI":"10.1111\/mmi.12685","type":"journal-article","created":{"date-parts":[[2014,6,26]],"date-time":"2014-06-26T15:53:00Z","timestamp":1403797980000},"page":"698-712","source":"Crossref","is-referenced-by-count":67,"title":["A vacuolar\u2010<scp>H<\/scp><sup>+<\/sup>\u2010pyrophosphatase (<scp>TgVP<\/scp>1) is required for microneme secretion, host cell invasion, and extracellular survival of <scp><i>T<\/i><\/scp><i>oxoplasma gondii<\/i>"],"prefix":"10.1111","volume":"93","author":[{"given":"Jing","family":"Liu","sequence":"first","affiliation":[{"name":"Center for Tropical and Emerging Global Diseases and Department of Cellular Biology University of Georgia  GA 30602\u20107400 USA"},{"name":"College of Veterinary Medicine China Agricultural University  Beijing 100193 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas","family":"Pace","sequence":"additional","affiliation":[{"name":"Center for Tropical and Emerging Global Diseases and Department of Cellular Biology University of Georgia  GA 30602\u20107400 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhicheng","family":"Dou","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology University of Michigan Medical School  Ann Arbor MI 48109\u20105620 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thayer P.","family":"King","sequence":"additional","affiliation":[{"name":"Center for Tropical and Emerging Global Diseases and Department of Cellular Biology University of Georgia  GA 30602\u20107400 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Guidot","sequence":"additional","affiliation":[{"name":"Center for Tropical and Emerging Global Diseases and Department of Cellular Biology University of Georgia  GA 30602\u20107400 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhu\u2010Hong","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Tropical and Emerging Global Diseases and Department of Cellular Biology University of Georgia  GA 30602\u20107400 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vern B.","family":"Carruthers","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology University of Michigan Medical School  Ann Arbor MI 48109\u20105620 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia N. J.","family":"Moreno","sequence":"additional","affiliation":[{"name":"Center for Tropical and Emerging Global Diseases and Department of Cellular Biology University of Georgia  GA 30602\u20107400 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,7,16]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.153.3740.1120"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(99)90617-8"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.arplant.47.1.159"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1993.tb18303.x"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M210341200"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2011.01597.x"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.21.7972"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2009.12.002"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1462-5822.1999.00023.x"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.115.3.599"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2011.05.012"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1360-1385(01)01923-9"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209436200"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1550-7408.1990.tb05883.x"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.4161\/psb.7.1.18573"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00357-08"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2011.03.020"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.186.19.6651-6655.2004"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.191389398"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0403139101"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)83641-4"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0143-4160(96)90084-6"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00037.2007"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00358-08"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.120212"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2004.04.004"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2010.01509.x"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1080\/07315724.2007.10719667"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204744200"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1115711"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10963"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1876"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.186.16.5418-5426.2004"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.1.55"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2004.04464.x"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/pcp\/pcn090"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(01)00251-1"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2736(00)00130-9"},{"key":"e_1_2_6_40_1","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1042\/bj3470243","article-title":"Acidocalcisomes and a vacuolar H+\u2010pyrophosphatase in malaria parasites","volume":"347","author":"Marchesini N.","year":"2000","journal-title":"Biochem J"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2010.07165.x"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3130655"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3300853"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20110641"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0509512102"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2010.07181.x"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2010.02.003"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1095-6433(01)00429-9"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3490737"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(02)00277-3"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0018390"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.34.22151"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1080\/15216540701258132"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M304548200"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M406099200"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.01495"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plaphy.2010.09.014"}],"container-title":["Molecular Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fmmi.12685","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/mmi.12685","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T11:07:31Z","timestamp":1696244851000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/mmi.12685"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,7,16]]},"references-count":56,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2014,8]]}},"alternative-id":["10.1111\/mmi.12685"],"URL":"https:\/\/doi.org\/10.1111\/mmi.12685","archive":["Portico"],"relation":{},"ISSN":["0950-382X","1365-2958"],"issn-type":[{"value":"0950-382X","type":"print"},{"value":"1365-2958","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,7,16]]}}}