{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T10:53:26Z","timestamp":1761216806004},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2004,10,6]],"date-time":"2004-10-06T00:00:00Z","timestamp":1097020800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2004,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Different species of <jats:italic>Leishmania<\/jats:italic> are responsible for the diverse pathologies associated with leishmaniasis including <jats:italic>Leishmania donovani<\/jats:italic> which results in fatal visceral infection and <jats:italic>Leishmania major<\/jats:italic> which causes non\u2010fatal cutaneous infection. In an attempt to identify genotypic differences between these related Old World <jats:italic>Leishmania<\/jats:italic> species which contribute to their distinct phenotypic characteristics, we have introduced a <jats:italic>L. donovani<\/jats:italic> cosmid library into <jats:italic>L. major<\/jats:italic> to select for <jats:italic>L. donovani<\/jats:italic> sequences which may increase <jats:italic>L. major<\/jats:italic> virulence in BALB\/c mice. Through this approach, we have identified a region of the <jats:italic>L. donovani<\/jats:italic> genome which increased virulence in both visceral and cutaneous sites and was divergent from the corresponding region of the <jats:italic>L. major<\/jats:italic> genome. When these <jats:italic>L. donovani<\/jats:italic> sequences were reintroduced into <jats:italic>L. major<\/jats:italic>, they enhanced the overall virulence of <jats:italic>L. major<\/jats:italic>, increasing its ability to survive in both visceral and cutaneous sites. The region responsible for increased infection levels was determined to be the miniexon gene array derived from chromosome 36 of <jats:italic>L. donovani.<\/jats:italic> Pulse field electrophoresis revealed that <jats:italic>L. donovani<\/jats:italic> contained miniexon gene sequences in several chromosome locations as opposed to <jats:italic>L. major<\/jats:italic> which contains miniexon gene sequences only in chromosome 2. Because of the requirement for miniexon\u2010derived transcripts in maturation of pre\u2010mRNAs in trypanosomatids, this observation suggests that the increased expression of miniexon genes is associated with increased virulence. As the genome sequence for <jats:italic>Leishmania<\/jats:italic> becomes available, the <jats:italic>in vivo<\/jats:italic> selection procedure described within will be useful to identify additional species\u2010specific sequences responsible for different pathogenic phenotypes associated with <jats:italic>Leishmania<\/jats:italic> infection.<\/jats:p>","DOI":"10.1111\/j.1365-2958.2004.04327.x","type":"journal-article","created":{"date-parts":[[2004,11,5]],"date-time":"2004-11-05T15:54:15Z","timestamp":1099670055000},"page":"1051-1062","source":"Crossref","is-referenced-by-count":14,"title":["<i>In vivo<\/i> selection for <i>Leishmania donovani<\/i> miniexon genes that increase virulence in <i>Leishmania major<\/i><sup>\u2020<\/sup>"],"prefix":"10.1111","volume":"54","author":[{"given":"Wen\u2010Wei","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Greg","family":"Matlashewski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,10,8]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/22.11.1959"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(99)00232-7"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/clind\/24.4.684"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2003.09.005"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.29.17081"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0035-9203(01)90223-8"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2003.11.012"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)10178-2"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-6851(89)90009-1"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-6851(94)90114-7"},{"key":"e_1_2_6_12_1","doi-asserted-by":"crossref","first-page":"2378","DOI":"10.1002\/j.1460-2075.1984.tb02144.x","article-title":"Discontinuous synthesis of mRNA in Trypanosomes","volume":"3","author":"Kooter J.M.","year":"1984","journal-title":"EMBO J"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/15.24.10087"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.10.6602"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(84)90552-X"},{"key":"e_1_2_6_16_1","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1128\/iai.38.3.1223-1230.1982","article-title":"Host\u2010parasite relationship in murine Leishmaniasis: pathophysiological and immunological changes","volume":"38","author":"Reiner N.E.","year":"1982","journal-title":"Infect Immun"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.6701528"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-6851(87)90092-2"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.30.18689"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(86)90617-3"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0020-7519(02)00131-5"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M304295200"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.16.8807"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02286.x"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/23.20.4073"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M305030200"}],"container-title":["Molecular Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2958.2004.04327.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-2958.2004.04327.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T02:47:35Z","timestamp":1695782855000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2958.2004.04327.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,10,8]]},"references-count":25,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2004,11]]}},"alternative-id":["10.1111\/j.1365-2958.2004.04327.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-2958.2004.04327.x","archive":["Portico"],"relation":{},"ISSN":["0950-382X","1365-2958"],"issn-type":[{"value":"0950-382X","type":"print"},{"value":"1365-2958","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,10,8]]}}}