Leishmania tropica: cysteine proteases are essential for growth and pathogenicity
Leishmania parasites are responsible for a diverse collection of diseases of humans and other animals. Cysteine proteases are putative virulence factors of leishmania parasites. There are differences in the susceptibility of specific stages in different Leishmania species to cysteine protease inhibi...
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| Veröffentlicht in: | Experimental parasitology 2004-03, Vol.106 (3), p.158-163 |
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| creator | Mahmoudzadeh-Niknam, H. McKerrow, J.H. |
| description | Leishmania parasites are responsible for a diverse collection of diseases of humans and other animals. Cysteine proteases are putative virulence factors of leishmania parasites. There are differences in the susceptibility of specific stages in different Leishmania species to cysteine protease inhibitors. Here, we establish a key role of cysteine proteases in growth, viability, and pathogenicity of
Leishmania tropica by using a specific cysteine protease inhibitor (
N-Pip-F-hF-VS Phenyl). Reduction or arrest of promastigote growth occurred at inhibitor concentration of 5 and 100
μM, respectively. This shows an essential role for cysteine proteases in viability and growth of
L. tropica promastigotes. It confirms that the promastigote stage of
L. tropica more closely resembles that of
Leishmania major than that of
Leishmania mexicana, which is refractory to this inhibitor. Pathogenicity of
L. tropica amastigotes in mice, as assessed by footpad swelling, was also reduced by treatment with the cysteine protease inhibitor. This suggests that cysteine proteases are essential for pathogenicity of
L. tropica amastigote in mammalian host, similar to both
L. major and
L. mexicana. |
| doi_str_mv | 10.1016/j.exppara.2004.03.005 |
| format | Article |
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Leishmania tropica by using a specific cysteine protease inhibitor (
N-Pip-F-hF-VS Phenyl). Reduction or arrest of promastigote growth occurred at inhibitor concentration of 5 and 100
μM, respectively. This shows an essential role for cysteine proteases in viability and growth of
L. tropica promastigotes. It confirms that the promastigote stage of
L. tropica more closely resembles that of
Leishmania major than that of
Leishmania mexicana, which is refractory to this inhibitor. Pathogenicity of
L. tropica amastigotes in mice, as assessed by footpad swelling, was also reduced by treatment with the cysteine protease inhibitor. This suggests that cysteine proteases are essential for pathogenicity of
L. tropica amastigote in mammalian host, similar to both
L. major and
L. mexicana.</description><identifier>ISSN: 0014-4894</identifier><identifier>EISSN: 1090-2449</identifier><identifier>DOI: 10.1016/j.exppara.2004.03.005</identifier><identifier>PMID: 15172223</identifier><identifier>CODEN: EXPAAA</identifier><language>eng</language><publisher>San Diego, CA: Elsevier Inc</publisher><subject>Animals ; Biological and medical sciences ; Cysteine Endopeptidases - physiology ; Cysteine protease ; Cysteine Proteinase Inhibitors - pharmacology ; Dipeptides - pharmacology ; Dose-Response Relationship, Drug ; Female ; Fundamental and applied biological sciences. Psychology ; Humans ; Leishmania major ; Leishmania major - enzymology ; Leishmania major - growth & development ; Leishmania major - pathogenicity ; Leishmania mexicana ; Leishmania tropica ; Leishmania tropica - enzymology ; Leishmania tropica - growth & development ; Leishmania tropica - pathogenicity ; Leishmaniasis ; Leishmaniasis, Cutaneous - enzymology ; Leishmaniasis, Cutaneous - parasitology ; Life cycle. Host-agent relationship. Pathogenesis ; Mice ; Protease inhibitor ; Protozoa ; Vinyl Compounds - pharmacology ; Virulence - physiology</subject><ispartof>Experimental parasitology, 2004-03, Vol.106 (3), p.158-163</ispartof><rights>2004 Elsevier Inc.</rights><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c422t-1051e5956d7507e55bd88d5a43a3d269a15ed29937aceff1702008a75e3e2aed3</citedby><cites>FETCH-LOGICAL-c422t-1051e5956d7507e55bd88d5a43a3d269a15ed29937aceff1702008a75e3e2aed3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0014489404000529$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15838897$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15172223$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mahmoudzadeh-Niknam, H.</creatorcontrib><creatorcontrib>McKerrow, J.H.</creatorcontrib><title>Leishmania tropica: cysteine proteases are essential for growth and pathogenicity</title><title>Experimental parasitology</title><addtitle>Exp Parasitol</addtitle><description>Leishmania parasites are responsible for a diverse collection of diseases of humans and other animals. Cysteine proteases are putative virulence factors of leishmania parasites. There are differences in the susceptibility of specific stages in different Leishmania species to cysteine protease inhibitors. Here, we establish a key role of cysteine proteases in growth, viability, and pathogenicity of
Leishmania tropica by using a specific cysteine protease inhibitor (
N-Pip-F-hF-VS Phenyl). Reduction or arrest of promastigote growth occurred at inhibitor concentration of 5 and 100
μM, respectively. This shows an essential role for cysteine proteases in viability and growth of
L. tropica promastigotes. It confirms that the promastigote stage of
L. tropica more closely resembles that of
Leishmania major than that of
Leishmania mexicana, which is refractory to this inhibitor. Pathogenicity of
L. tropica amastigotes in mice, as assessed by footpad swelling, was also reduced by treatment with the cysteine protease inhibitor. This suggests that cysteine proteases are essential for pathogenicity of
L. tropica amastigote in mammalian host, similar to both
L. major and
L. mexicana.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cysteine Endopeptidases - physiology</subject><subject>Cysteine protease</subject><subject>Cysteine Proteinase Inhibitors - pharmacology</subject><subject>Dipeptides - pharmacology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Leishmania major</subject><subject>Leishmania major - enzymology</subject><subject>Leishmania major - growth & development</subject><subject>Leishmania major - pathogenicity</subject><subject>Leishmania mexicana</subject><subject>Leishmania tropica</subject><subject>Leishmania tropica - enzymology</subject><subject>Leishmania tropica - growth & development</subject><subject>Leishmania tropica - pathogenicity</subject><subject>Leishmaniasis</subject><subject>Leishmaniasis, Cutaneous - enzymology</subject><subject>Leishmaniasis, Cutaneous - parasitology</subject><subject>Life cycle. Host-agent relationship. Pathogenesis</subject><subject>Mice</subject><subject>Protease inhibitor</subject><subject>Protozoa</subject><subject>Vinyl Compounds - pharmacology</subject><subject>Virulence - physiology</subject><issn>0014-4894</issn><issn>1090-2449</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1v1DAQhi1ERZfCTwD5AreE8VeccEGo4ktaqUKCszW1J12vskmwvZT996TaSHDraS7PO_POw9grAbUA0bzb1_RnnjFhLQF0DaoGME_YRkAHldS6e8o2AEJXuu30JXue8x4AWiH1M3YpjLBSSrVh37cU8-6AY0Re0jRHj--5P-VCcSQ-p6kQZsocE3HKmcYSceD9lPhdmu7LjuMY-IxlN93RGH0spxfsosch08t1XrGfnz_9uP5abW--fLv-uK28lrJUAowg05kmWAOWjLkNbRsMaoUqyKZDYSjIrlMWPfW9sLD82aI1pEgiBXXF3p73LiV_HSkXd4jZ0zDgSNMxO2FtI5VoFtCcQZ-mnBP1bk7xgOnkBLgHl27vVpfuwaUD5RaXS-71euB4e6DwL7XKW4A3K4DZ49AnHH3M_3GtatvOLtyHM0eLjt-Rkss-0ugpxES-uDDFR6r8BaS1lZs</recordid><startdate>20040301</startdate><enddate>20040301</enddate><creator>Mahmoudzadeh-Niknam, H.</creator><creator>McKerrow, J.H.</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><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>M7N</scope></search><sort><creationdate>20040301</creationdate><title>Leishmania tropica: cysteine proteases are essential for growth and pathogenicity</title><author>Mahmoudzadeh-Niknam, H. ; McKerrow, J.H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c422t-1051e5956d7507e55bd88d5a43a3d269a15ed29937aceff1702008a75e3e2aed3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cysteine Endopeptidases - physiology</topic><topic>Cysteine protease</topic><topic>Cysteine Proteinase Inhibitors - pharmacology</topic><topic>Dipeptides - pharmacology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Leishmania major</topic><topic>Leishmania major - enzymology</topic><topic>Leishmania major - growth & development</topic><topic>Leishmania major - pathogenicity</topic><topic>Leishmania mexicana</topic><topic>Leishmania tropica</topic><topic>Leishmania tropica - enzymology</topic><topic>Leishmania tropica - growth & development</topic><topic>Leishmania tropica - pathogenicity</topic><topic>Leishmaniasis</topic><topic>Leishmaniasis, Cutaneous - enzymology</topic><topic>Leishmaniasis, Cutaneous - parasitology</topic><topic>Life cycle. Host-agent relationship. Pathogenesis</topic><topic>Mice</topic><topic>Protease inhibitor</topic><topic>Protozoa</topic><topic>Vinyl Compounds - pharmacology</topic><topic>Virulence - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mahmoudzadeh-Niknam, H.</creatorcontrib><creatorcontrib>McKerrow, J.H.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><jtitle>Experimental parasitology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mahmoudzadeh-Niknam, H.</au><au>McKerrow, J.H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Leishmania tropica: cysteine proteases are essential for growth and pathogenicity</atitle><jtitle>Experimental parasitology</jtitle><addtitle>Exp Parasitol</addtitle><date>2004-03-01</date><risdate>2004</risdate><volume>106</volume><issue>3</issue><spage>158</spage><epage>163</epage><pages>158-163</pages><issn>0014-4894</issn><eissn>1090-2449</eissn><coden>EXPAAA</coden><abstract>Leishmania parasites are responsible for a diverse collection of diseases of humans and other animals. Cysteine proteases are putative virulence factors of leishmania parasites. There are differences in the susceptibility of specific stages in different Leishmania species to cysteine protease inhibitors. Here, we establish a key role of cysteine proteases in growth, viability, and pathogenicity of
Leishmania tropica by using a specific cysteine protease inhibitor (
N-Pip-F-hF-VS Phenyl). Reduction or arrest of promastigote growth occurred at inhibitor concentration of 5 and 100
μM, respectively. This shows an essential role for cysteine proteases in viability and growth of
L. tropica promastigotes. It confirms that the promastigote stage of
L. tropica more closely resembles that of
Leishmania major than that of
Leishmania mexicana, which is refractory to this inhibitor. Pathogenicity of
L. tropica amastigotes in mice, as assessed by footpad swelling, was also reduced by treatment with the cysteine protease inhibitor. This suggests that cysteine proteases are essential for pathogenicity of
L. tropica amastigote in mammalian host, similar to both
L. major and
L. mexicana.</abstract><cop>San Diego, CA</cop><pub>Elsevier Inc</pub><pmid>15172223</pmid><doi>10.1016/j.exppara.2004.03.005</doi><tpages>6</tpages></addata></record> |
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| subjects | Animals Biological and medical sciences Cysteine Endopeptidases - physiology Cysteine protease Cysteine Proteinase Inhibitors - pharmacology Dipeptides - pharmacology Dose-Response Relationship, Drug Female Fundamental and applied biological sciences. Psychology Humans Leishmania major Leishmania major - enzymology Leishmania major - growth & development Leishmania major - pathogenicity Leishmania mexicana Leishmania tropica Leishmania tropica - enzymology Leishmania tropica - growth & development Leishmania tropica - pathogenicity Leishmaniasis Leishmaniasis, Cutaneous - enzymology Leishmaniasis, Cutaneous - parasitology Life cycle. Host-agent relationship. Pathogenesis Mice Protease inhibitor Protozoa Vinyl Compounds - pharmacology Virulence - physiology |
| title | Leishmania tropica: cysteine proteases are essential for growth and pathogenicity |
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