Targeted gene deletion in Leishmania major identifies leishmanolysin (GP63) as a virulence factor
Leishmanolysin, the Leishmania surface metalloproteinase of 63 kDa (GP63) has been described as a parasite virulence factor and is involved in the direct interaction of promastigotes and host macrophage receptors and interaction with the complement cascade. To study the role of leishmanolysin in the...
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| Veröffentlicht in: | Molecular and biochemical parasitology 2002-03, Vol.120 (1), p.33-40 |
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| creator | Joshi, Phalgun B. Kelly, Ben L. Kamhawi, Shaden Sacks, David L. McMaster, W.Robert |
| description | Leishmanolysin, the
Leishmania surface metalloproteinase of 63 kDa (GP63) has been described as a parasite virulence factor and is involved in the direct interaction of promastigotes and host macrophage receptors and interaction with the complement cascade. To study the role of leishmanolysin in the pathogenesis and virulence of
Leishmania major, targeted gene replacement was used to delete the entire 20 kb region containing all seven leishmanolysin genes (
gp63 genes 1–7). The resulting
L. major leishmanolysin deficient mutants showed normal development inside the sand fly vector, however, promastigotes recovered from sand flies or from culture showed an increase in sensitivity to complement-mediated lysis and a delay in lesion formation in BALB/c animals. The phenotypic differences could be significantly improved by expression of a cloned leishmanolysin gene. These results demonstrate that leishmanolysin is a vital virulence factor in
Leishmania pathogenesis. |
| doi_str_mv | 10.1016/S0166-6851(01)00432-7 |
| format | Article |
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Leishmania surface metalloproteinase of 63 kDa (GP63) has been described as a parasite virulence factor and is involved in the direct interaction of promastigotes and host macrophage receptors and interaction with the complement cascade. To study the role of leishmanolysin in the pathogenesis and virulence of
Leishmania major, targeted gene replacement was used to delete the entire 20 kb region containing all seven leishmanolysin genes (
gp63 genes 1–7). The resulting
L. major leishmanolysin deficient mutants showed normal development inside the sand fly vector, however, promastigotes recovered from sand flies or from culture showed an increase in sensitivity to complement-mediated lysis and a delay in lesion formation in BALB/c animals. The phenotypic differences could be significantly improved by expression of a cloned leishmanolysin gene. These results demonstrate that leishmanolysin is a vital virulence factor in
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Leishmania surface metalloproteinase of 63 kDa (GP63) has been described as a parasite virulence factor and is involved in the direct interaction of promastigotes and host macrophage receptors and interaction with the complement cascade. To study the role of leishmanolysin in the pathogenesis and virulence of
Leishmania major, targeted gene replacement was used to delete the entire 20 kb region containing all seven leishmanolysin genes (
gp63 genes 1–7). The resulting
L. major leishmanolysin deficient mutants showed normal development inside the sand fly vector, however, promastigotes recovered from sand flies or from culture showed an increase in sensitivity to complement-mediated lysis and a delay in lesion formation in BALB/c animals. The phenotypic differences could be significantly improved by expression of a cloned leishmanolysin gene. These results demonstrate that leishmanolysin is a vital virulence factor in
Leishmania pathogenesis.</description><subject>Animals</subject><subject>Complement</subject><subject>Complement System Proteins - immunology</subject><subject>Gene Deletion</subject><subject>Gene Targeting</subject><subject>Leishmania major - genetics</subject><subject>Leishmania major - growth & development</subject><subject>Leishmania major - pathogenicity</subject><subject>Leishmaniasis, Cutaneous - parasitology</subject><subject>Leishmaniasis, Cutaneous - physiopathology</subject><subject>Leishmanolysin</subject><subject>Metalloendopeptidases - genetics</subject><subject>Metalloendopeptidases - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Parasitic–protozoan</subject><subject>Phlebotomus - parasitology</subject><subject>Transgenic/knockout</subject><subject>Virulence</subject><issn>0166-6851</issn><issn>1872-9428</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1rGzEQhkVJSVwnP6FFp-AcNhmtVivtqQTTpgFDA_FdzEqjVGE_UmkdyL_vujbtMSBGh3lmBp6Xsc8CrgWI-uZxLnVRGyVWIK4AKlkW-gNbCKPLoqlKc8IW_5Az9innZwBQuq5P2ZkQpmo0yAXDLaYnmsjzJxqIe-poiuPA48A3FPOvHoeIvMfnMfHoaZhiiJR5d-yN3Vue0dXdQy2vOGaO_DWmXUeDIx7QTWM6Zx8Ddpkujv-Sbb9_265_FJufd_fr203hZFNOhQ7BV9IZrFtqG4lVCZVGFKbF0lXkJSmBAC4YCRpCi40K3imhZe1AGrlkl4e1L2n8vaM82T5mR12HA427bLWolJZKvQvOaqQwqplBdQBdGnNOFOxLij2mNyvA7jOwfzOwe8EW5rfPwOp57svxwK7tyf-fOkqfga8HgGYdr5GSzS7ujfmYyE3Wj_GdE38AASaWfw</recordid><startdate>20020301</startdate><enddate>20020301</enddate><creator>Joshi, Phalgun B.</creator><creator>Kelly, Ben L.</creator><creator>Kamhawi, Shaden</creator><creator>Sacks, David L.</creator><creator>McMaster, W.Robert</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20020301</creationdate><title>Targeted gene deletion in Leishmania major identifies leishmanolysin (GP63) as a virulence factor</title><author>Joshi, Phalgun B. ; Kelly, Ben L. ; Kamhawi, Shaden ; Sacks, David L. ; McMaster, W.Robert</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c392t-7ffd43c8a6beb93a42047aa18ba2c4ed3e51a00cf83070fba95fdc51736c0383</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Animals</topic><topic>Complement</topic><topic>Complement System Proteins - immunology</topic><topic>Gene Deletion</topic><topic>Gene Targeting</topic><topic>Leishmania major - genetics</topic><topic>Leishmania major - growth & development</topic><topic>Leishmania major - pathogenicity</topic><topic>Leishmaniasis, Cutaneous - parasitology</topic><topic>Leishmaniasis, Cutaneous - physiopathology</topic><topic>Leishmanolysin</topic><topic>Metalloendopeptidases - genetics</topic><topic>Metalloendopeptidases - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Parasitic–protozoan</topic><topic>Phlebotomus - parasitology</topic><topic>Transgenic/knockout</topic><topic>Virulence</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Joshi, Phalgun B.</creatorcontrib><creatorcontrib>Kelly, Ben L.</creatorcontrib><creatorcontrib>Kamhawi, Shaden</creatorcontrib><creatorcontrib>Sacks, David L.</creatorcontrib><creatorcontrib>McMaster, W.Robert</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular and biochemical parasitology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Joshi, Phalgun B.</au><au>Kelly, Ben L.</au><au>Kamhawi, Shaden</au><au>Sacks, David L.</au><au>McMaster, W.Robert</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Targeted gene deletion in Leishmania major identifies leishmanolysin (GP63) as a virulence factor</atitle><jtitle>Molecular and biochemical parasitology</jtitle><addtitle>Mol Biochem Parasitol</addtitle><date>2002-03-01</date><risdate>2002</risdate><volume>120</volume><issue>1</issue><spage>33</spage><epage>40</epage><pages>33-40</pages><issn>0166-6851</issn><eissn>1872-9428</eissn><abstract>Leishmanolysin, the
Leishmania surface metalloproteinase of 63 kDa (GP63) has been described as a parasite virulence factor and is involved in the direct interaction of promastigotes and host macrophage receptors and interaction with the complement cascade. To study the role of leishmanolysin in the pathogenesis and virulence of
Leishmania major, targeted gene replacement was used to delete the entire 20 kb region containing all seven leishmanolysin genes (
gp63 genes 1–7). The resulting
L. major leishmanolysin deficient mutants showed normal development inside the sand fly vector, however, promastigotes recovered from sand flies or from culture showed an increase in sensitivity to complement-mediated lysis and a delay in lesion formation in BALB/c animals. The phenotypic differences could be significantly improved by expression of a cloned leishmanolysin gene. These results demonstrate that leishmanolysin is a vital virulence factor in
Leishmania pathogenesis.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>11849703</pmid><doi>10.1016/S0166-6851(01)00432-7</doi><tpages>8</tpages></addata></record> |
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| ispartof | Molecular and biochemical parasitology, 2002-03, Vol.120 (1), p.33-40 |
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| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animals Complement Complement System Proteins - immunology Gene Deletion Gene Targeting Leishmania major - genetics Leishmania major - growth & development Leishmania major - pathogenicity Leishmaniasis, Cutaneous - parasitology Leishmaniasis, Cutaneous - physiopathology Leishmanolysin Metalloendopeptidases - genetics Metalloendopeptidases - metabolism Mice Mice, Inbred BALB C Parasitic–protozoan Phlebotomus - parasitology Transgenic/knockout Virulence |
| title | Targeted gene deletion in Leishmania major identifies leishmanolysin (GP63) as a virulence factor |
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