Regulation of Differentiation to the Infective Stage of the Protozoan Parasite Leishmania major by Tetrahydrobiopterin
A critical step in the infectious cycle of Leishmania is the differentiation of parasites within the sand fly vector to the highly infective metacyclic promastigote stage. Here, we establish tetrahydrobiopterin (H4B) levels as an important factor controlling the extent of metacyclogenesis. H4Blevels...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2001-04, Vol.292 (5515), p.285-287 |
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| creator | Cunningham, Mark L. Titus, Richard G. Turco, Salvatore J. Beverley, Stephen M. |
| description | A critical step in the infectious cycle of Leishmania is the differentiation of parasites within the sand fly vector to the highly infective metacyclic promastigote stage. Here, we establish tetrahydrobiopterin (H4B) levels as an important factor controlling the extent of metacyclogenesis. H4Blevels decline substantially during normal development, and genetic or nutritional manipulations showed that low H4Bcaused elevated metacyclogenesis. Mutants lacking pteridine reductase 1 (PTR1) had low levels of H4B, remained infectious to mice, and induced larger cutaneous lesions (hypervirulence). Thus, the control of pteridine metabolism has relevance to the mechanism of Leishmania differentiation and the limitation of virulence during evolution. |
| doi_str_mv | 10.1126/science.1057740 |
| format | Article |
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Here, we establish tetrahydrobiopterin (H4B) levels as an important factor controlling the extent of metacyclogenesis. H4Blevels decline substantially during normal development, and genetic or nutritional manipulations showed that low H4Bcaused elevated metacyclogenesis. Mutants lacking pteridine reductase 1 (PTR1) had low levels of H4B, remained infectious to mice, and induced larger cutaneous lesions (hypervirulence). Thus, the control of pteridine metabolism has relevance to the mechanism of Leishmania differentiation and the limitation of virulence during evolution.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.1057740</identifier><identifier>PMID: 11303103</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>Washington, DC: American Society for the Advancement of Science</publisher><subject>Animals ; Biochemistry ; Biological and medical sciences ; Biopterins - analogs & derivatives ; Biopterins - metabolism ; Biopterins - pharmacology ; Carrier Proteins - genetics ; Carrier Proteins - metabolism ; Chromatography, High Pressure Liquid ; Evolution ; Folic Acid - metabolism ; Fundamental and applied biological sciences. Psychology ; Genes, Protozoan ; Genetics ; Glycosphingolipids - analysis ; Human protozoal diseases ; Individualized Instruction ; Infectious diseases ; Leishmania major ; Leishmania major - genetics ; Leishmania major - growth & development ; Leishmania major - metabolism ; Leishmania major - pathogenicity ; Leishmaniasis ; Leishmaniasis, Cutaneous - parasitology ; Leshmaniasis ; Lesions ; Life cycle. Host-agent relationship. Pathogenesis ; Medical sciences ; Membrane Transport Proteins ; Metabolism ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data ; Mutation ; Nutrition ; Oxidoreductases - genetics ; Oxidoreductases - metabolism ; Parasite hosts ; Parasites ; Parasitic diseases ; Parasitism ; Promastigotes ; Protozoa ; Protozoal diseases ; Protozoan Proteins ; pteridine ; pteridine reductase 1 ; Pteridines ; Signal Transduction ; Steepest descent method ; tetrahydrobiopterin ; Virulence</subject><ispartof>Science (American Association for the Advancement of Science), 2001-04, Vol.292 (5515), p.285-287</ispartof><rights>Copyright 2001 American Association for the Advancement of Science</rights><rights>2001 INIST-CNRS</rights><rights>COPYRIGHT 2001 American Association for the Advancement of Science</rights><rights>COPYRIGHT 2001 American Association for the Advancement of Science</rights><rights>Copyright American Association for the Advancement of Science Apr 13, 2001</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c737t-9ba706e14ad033772d828f0ddaf74052715dca4a5f759fbeb92ea1ea668300183</citedby><cites>FETCH-LOGICAL-c737t-9ba706e14ad033772d828f0ddaf74052715dca4a5f759fbeb92ea1ea668300183</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/3082736$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/3082736$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,776,780,799,2871,2872,27901,27902,57992,58225</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=954350$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11303103$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cunningham, Mark L.</creatorcontrib><creatorcontrib>Titus, Richard G.</creatorcontrib><creatorcontrib>Turco, Salvatore J.</creatorcontrib><creatorcontrib>Beverley, Stephen M.</creatorcontrib><title>Regulation of Differentiation to the Infective Stage of the Protozoan Parasite Leishmania major by Tetrahydrobiopterin</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>A critical step in the infectious cycle of Leishmania is the differentiation of parasites within the sand fly vector to the highly infective metacyclic promastigote stage. Here, we establish tetrahydrobiopterin (H4B) levels as an important factor controlling the extent of metacyclogenesis. H4Blevels decline substantially during normal development, and genetic or nutritional manipulations showed that low H4Bcaused elevated metacyclogenesis. Mutants lacking pteridine reductase 1 (PTR1) had low levels of H4B, remained infectious to mice, and induced larger cutaneous lesions (hypervirulence). Thus, the control of pteridine metabolism has relevance to the mechanism of Leishmania differentiation and the limitation of virulence during evolution.</description><subject>Animals</subject><subject>Biochemistry</subject><subject>Biological and medical sciences</subject><subject>Biopterins - analogs & derivatives</subject><subject>Biopterins - metabolism</subject><subject>Biopterins - pharmacology</subject><subject>Carrier Proteins - genetics</subject><subject>Carrier Proteins - metabolism</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Evolution</subject><subject>Folic Acid - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genes, Protozoan</subject><subject>Genetics</subject><subject>Glycosphingolipids - analysis</subject><subject>Human protozoal diseases</subject><subject>Individualized Instruction</subject><subject>Infectious diseases</subject><subject>Leishmania major</subject><subject>Leishmania major - genetics</subject><subject>Leishmania major - growth & development</subject><subject>Leishmania major - metabolism</subject><subject>Leishmania major - pathogenicity</subject><subject>Leishmaniasis</subject><subject>Leishmaniasis, Cutaneous - parasitology</subject><subject>Leshmaniasis</subject><subject>Lesions</subject><subject>Life cycle. Host-agent relationship. 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Titus, Richard G. ; Turco, Salvatore J. ; Beverley, Stephen M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c737t-9ba706e14ad033772d828f0ddaf74052715dca4a5f759fbeb92ea1ea668300183</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Animals</topic><topic>Biochemistry</topic><topic>Biological and medical sciences</topic><topic>Biopterins - analogs & derivatives</topic><topic>Biopterins - metabolism</topic><topic>Biopterins - pharmacology</topic><topic>Carrier Proteins - genetics</topic><topic>Carrier Proteins - metabolism</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Evolution</topic><topic>Folic Acid - metabolism</topic><topic>Fundamental and applied biological sciences. 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M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Regulation of Differentiation to the Infective Stage of the Protozoan Parasite Leishmania major by Tetrahydrobiopterin</atitle><jtitle>Science (American Association for the Advancement of Science)</jtitle><addtitle>Science</addtitle><date>2001-04-13</date><risdate>2001</risdate><volume>292</volume><issue>5515</issue><spage>285</spage><epage>287</epage><pages>285-287</pages><issn>0036-8075</issn><eissn>1095-9203</eissn><coden>SCIEAS</coden><abstract>A critical step in the infectious cycle of Leishmania is the differentiation of parasites within the sand fly vector to the highly infective metacyclic promastigote stage. Here, we establish tetrahydrobiopterin (H4B) levels as an important factor controlling the extent of metacyclogenesis. H4Blevels decline substantially during normal development, and genetic or nutritional manipulations showed that low H4Bcaused elevated metacyclogenesis. Mutants lacking pteridine reductase 1 (PTR1) had low levels of H4B, remained infectious to mice, and induced larger cutaneous lesions (hypervirulence). Thus, the control of pteridine metabolism has relevance to the mechanism of Leishmania differentiation and the limitation of virulence during evolution.</abstract><cop>Washington, DC</cop><pub>American Society for the Advancement of Science</pub><pmid>11303103</pmid><doi>10.1126/science.1057740</doi><tpages>3</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0036-8075 |
| ispartof | Science (American Association for the Advancement of Science), 2001-04, Vol.292 (5515), p.285-287 |
| issn | 0036-8075 1095-9203 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_77056317 |
| source | American Association for the Advancement of Science; Jstor Complete Legacy; MEDLINE |
| subjects | Animals Biochemistry Biological and medical sciences Biopterins - analogs & derivatives Biopterins - metabolism Biopterins - pharmacology Carrier Proteins - genetics Carrier Proteins - metabolism Chromatography, High Pressure Liquid Evolution Folic Acid - metabolism Fundamental and applied biological sciences. Psychology Genes, Protozoan Genetics Glycosphingolipids - analysis Human protozoal diseases Individualized Instruction Infectious diseases Leishmania major Leishmania major - genetics Leishmania major - growth & development Leishmania major - metabolism Leishmania major - pathogenicity Leishmaniasis Leishmaniasis, Cutaneous - parasitology Leshmaniasis Lesions Life cycle. Host-agent relationship. Pathogenesis Medical sciences Membrane Transport Proteins Metabolism Mice Mice, Inbred BALB C Molecular Sequence Data Mutation Nutrition Oxidoreductases - genetics Oxidoreductases - metabolism Parasite hosts Parasites Parasitic diseases Parasitism Promastigotes Protozoa Protozoal diseases Protozoan Proteins pteridine pteridine reductase 1 Pteridines Signal Transduction Steepest descent method tetrahydrobiopterin Virulence |
| title | Regulation of Differentiation to the Infective Stage of the Protozoan Parasite Leishmania major by Tetrahydrobiopterin |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T18%3A14%3A55IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Regulation%20of%20Differentiation%20to%20the%20Infective%20Stage%20of%20the%20Protozoan%20Parasite%20Leishmania%20major%20by%20Tetrahydrobiopterin&rft.jtitle=Science%20(American%20Association%20for%20the%20Advancement%20of%20Science)&rft.au=Cunningham,%20Mark%20L.&rft.date=2001-04-13&rft.volume=292&rft.issue=5515&rft.spage=285&rft.epage=287&rft.pages=285-287&rft.issn=0036-8075&rft.eissn=1095-9203&rft.coden=SCIEAS&rft_id=info:doi/10.1126/science.1057740&rft_dat=%3Cgale_proqu%3EA73828078%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=213584893&rft_id=info:pmid/11303103&rft_galeid=A73828078&rft_jstor_id=3082736&rfr_iscdi=true |