{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T07:29:40Z","timestamp":1775978980915,"version":"3.50.1"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Molecular Biol"],"published-print":{"date-parts":[[2006,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Visceral leishmaniasis caused by members of the<jats:italic>Leishmania donovani<\/jats:italic>complex is often fatal in the absence of treatment. Research has been hampered by the lack of good laboratory models and tools for genetic manipulation. In this study, we have characterised a<jats:italic>L. infantum<\/jats:italic>line (JPCM5) that was isolated from a naturally infected dog and then cloned. We found that JPCM5 has attributes that make it an excellent laboratory model; different stages of the parasite life cycle can be studied<jats:italic>in vitro<\/jats:italic>, it is accessible to genetic manipulation and it has retained its virulence. Furthermore, the<jats:italic>L. infantum<\/jats:italic>JPCM5 genome has now been fully sequenced.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We have further focused our studies on<jats:italic>LiCPA<\/jats:italic>, the<jats:italic>L. infantum<\/jats:italic>homologue to<jats:italic>L. mexicana<\/jats:italic>cysteine peptidase CPA. LiCPA was found to share a high percentage of amino acid identity with CPA proteins of other<jats:italic>Leishmania<\/jats:italic>species. Two independent<jats:italic>LiCPA<\/jats:italic>-deficient promastigote clones (\u0394<jats:italic>Licpa<\/jats:italic>) were generated and their phenotype characterised. In contrast to<jats:italic>L. mexicana CPA<\/jats:italic>-deficient mutants, both clones of \u0394<jats:italic>Licpa<\/jats:italic>were found to have significantly reduced virulence<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>. Re-expression of just one<jats:italic>LiCPA<\/jats:italic>allele (giving \u0394<jats:italic>Licpa<\/jats:italic>::CPA) was sufficient to complement the reduced infectivity of both \u0394<jats:italic>Licpa<\/jats:italic>mutants for human macrophages, which confirms the importance of LiCPA for<jats:italic>L. infantum<\/jats:italic>virulence. In contrast,<jats:italic>in vivo<\/jats:italic>experiments did not show any virulence recovery of the re-expressor clone \u0394<jats:italic>Licpa<\/jats:italic>C1::CPA compared with the CPA-deficient mutant \u0394<jats:italic>Licpa<\/jats:italic>C1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The data suggest that CPA is not essential for replication of<jats:italic>L. infantum<\/jats:italic>promastigotes, but is important for the host-parasite interaction. Further studies will be necessary to elucidate the precise roles that LiCPA plays and why the re-expression of LiCPA in the \u0394<jats:italic>Licpa<\/jats:italic>mutants complemented the gene deletion phenotype only in<jats:italic>in vitro<\/jats:italic>and not in<jats:italic>in vivo<\/jats:italic>infection of hamsters.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1471-2199-7-42","type":"journal-article","created":{"date-parts":[[2006,11,14]],"date-time":"2006-11-14T07:18:21Z","timestamp":1163488701000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Studies on the CPA cysteine peptidase in the Leishmania infantum genome strain JPCM5"],"prefix":"10.1186","volume":"7","author":[{"given":"Hubert","family":"Denise","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacqueline","family":"Poot","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maribel","family":"Jim\u00e9nez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Audrey","family":"Ambit","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daland C","family":"Herrmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arno N","family":"Vermeulen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graham H","family":"Coombs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremy C","family":"Mottram","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2006,11,13]]},"reference":[{"key":"131_CR1","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1128\/CMR.10.2.298","volume":"10","author":"J Alvar","year":"1997","unstructured":"Alvar J, Ca\u00f1avate C, Guti\u00e9rrez-Solar B, Jim\u00e9nez M, Laguna F, L\u00f3pez-V\u00e9lez R, Molina R, Moreno J: Leishmania and human immunodeficiency virus coinfection: The first 10 years. 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