Mitochondrial genes for heme-dependent respiratory chain complexes are up-regulated after depletion of Wolbachia from filarial nematodes
The filarial nematodes Brugia malayi, Wuchereria bancrofti and Onchocerca volvulus cause elephantiasis or dermatitis and blindness resulting in severe morbidity. Annually, 1.3 billion people are at risk of infection. Targeting the essential Wolbachia endobacteria of filarial nematodes with doxycycli...
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| Veröffentlicht in: | International journal for parasitology 2010-08, Vol.40 (10), p.1193-1202 |
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| creator | Strübing, Uta Lucius, Richard Hoerauf, Achim Pfarr, Kenneth M. |
| description | The filarial nematodes
Brugia malayi,
Wuchereria bancrofti and
Onchocerca volvulus cause elephantiasis or dermatitis and blindness resulting in severe morbidity. Annually, 1.3 billion people are at risk of infection. Targeting the essential
Wolbachia endobacteria of filarial nematodes with doxycycline has proven to be an effective therapy resulting in a block in embryogenesis, worm development and macrofilaricidal effects. However, doxycycline is contraindicated for a large portion of the at risk population. To identify new targets for anti-wolbachial therapy, understanding the molecular basis of the
Wolbachia–filaria symbiosis is required. Using the
B. malayi microarray we identified differentially expressed genes in the rodent filaria
Litomosoides sigmodontis after depletion of
Wolbachia which might have a role in symbiosis. The microarray data were filtered for regulated genes with a false discovery rate |
| doi_str_mv | 10.1016/j.ijpara.2010.03.004 |
| format | Article |
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Brugia malayi,
Wuchereria bancrofti and
Onchocerca volvulus cause elephantiasis or dermatitis and blindness resulting in severe morbidity. Annually, 1.3 billion people are at risk of infection. Targeting the essential
Wolbachia endobacteria of filarial nematodes with doxycycline has proven to be an effective therapy resulting in a block in embryogenesis, worm development and macrofilaricidal effects. However, doxycycline is contraindicated for a large portion of the at risk population. To identify new targets for anti-wolbachial therapy, understanding the molecular basis of the
Wolbachia–filaria symbiosis is required. Using the
B. malayi microarray we identified differentially expressed genes in the rodent filaria
Litomosoides sigmodontis after depletion of
Wolbachia which might have a role in symbiosis. The microarray data were filtered for regulated genes with a false discovery rate <5% and a ⩾2-fold-change. Most of the genes were differentially expressed at day 36 of tetracycline treatment, when 99.8% of
Wolbachia were depleted. Several classes of genes were affected, including genes for translation, transcription, folding/sorting of proteins, motility, structure and metabolic and signalling pathways. Quantitative PCR validated 60% of the genes found to be regulated in the microarray. A nuclear encoded heme-binding protein of the globin family was up-regulated upon loss of
Wolbachia. Interestingly, mitochondrial encoded subunits of respiratory chain complexes containing heme and riboflavin were also up-regulated. No change in the expression of these genes was seen in tetracycline treated
Wolbachia-free
Acanthocheilonema viteae. As
Wolbachia synthesise heme and filaria do not, we hypothesise that without the endosymbionts no functional heme-containing enzymes can be formed, leading to loss of energy metabolism which then results in up-regulation of the mitochondrial encoded subunits in an attempt to correct the deviation from homeostasis. Our results support targeting the
Wolbachia heme synthesis pathway for the discovery of new anti-filarial drugs.</description><identifier>ISSN: 0020-7519</identifier><identifier>EISSN: 1879-0135</identifier><identifier>DOI: 10.1016/j.ijpara.2010.03.004</identifier><identifier>PMID: 20362581</identifier><identifier>CODEN: IJPYBT</identifier><language>eng</language><publisher>Kidlington: Elsevier Ltd</publisher><subject>Animals ; Anti-Bacterial Agents - pharmacology ; Biological and medical sciences ; Brugia malayi ; DNA, Complementary - genetics ; DNA, Complementary - metabolism ; Doxycycline - pharmacology ; Electron Transport - genetics ; Electron Transport - physiology ; Filariasis ; Filarioidea - genetics ; Filarioidea - metabolism ; Fundamental and applied biological sciences. Psychology ; Genes, Mitochondrial - genetics ; Genes, Mitochondrial - physiology ; Heme ; Invertebrates ; Life cycle. Host-agent relationship. Pathogenesis ; Litomosoides sigmodontis ; Microarray ; Mitochondria ; Molecular Sequence Data ; Nemathelminthia. Plathelmintha ; Nematoda ; Oligonucleotide Array Sequence Analysis ; Onchocerca volvulus ; Protozoa ; Symbiosis ; Tetracycline ; Up-Regulation ; Wolbachia ; Wolbachia - drug effects ; Wolbachia - physiology ; Wuchereria bancrofti</subject><ispartof>International journal for parasitology, 2010-08, Vol.40 (10), p.1193-1202</ispartof><rights>2010 Australian Society for Parasitology Inc.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright 2010 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c447t-e83320ba24e18bc4e69a1136bb4b702df108dd878957a131118796a4545e3b383</citedby><cites>FETCH-LOGICAL-c447t-e83320ba24e18bc4e69a1136bb4b702df108dd878957a131118796a4545e3b383</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ijpara.2010.03.004$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>309,310,314,780,784,789,790,3550,23930,23931,25140,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23005487$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20362581$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Strübing, Uta</creatorcontrib><creatorcontrib>Lucius, Richard</creatorcontrib><creatorcontrib>Hoerauf, Achim</creatorcontrib><creatorcontrib>Pfarr, Kenneth M.</creatorcontrib><title>Mitochondrial genes for heme-dependent respiratory chain complexes are up-regulated after depletion of Wolbachia from filarial nematodes</title><title>International journal for parasitology</title><addtitle>Int J Parasitol</addtitle><description>The filarial nematodes
Brugia malayi,
Wuchereria bancrofti and
Onchocerca volvulus cause elephantiasis or dermatitis and blindness resulting in severe morbidity. Annually, 1.3 billion people are at risk of infection. Targeting the essential
Wolbachia endobacteria of filarial nematodes with doxycycline has proven to be an effective therapy resulting in a block in embryogenesis, worm development and macrofilaricidal effects. However, doxycycline is contraindicated for a large portion of the at risk population. To identify new targets for anti-wolbachial therapy, understanding the molecular basis of the
Wolbachia–filaria symbiosis is required. Using the
B. malayi microarray we identified differentially expressed genes in the rodent filaria
Litomosoides sigmodontis after depletion of
Wolbachia which might have a role in symbiosis. The microarray data were filtered for regulated genes with a false discovery rate <5% and a ⩾2-fold-change. Most of the genes were differentially expressed at day 36 of tetracycline treatment, when 99.8% of
Wolbachia were depleted. Several classes of genes were affected, including genes for translation, transcription, folding/sorting of proteins, motility, structure and metabolic and signalling pathways. Quantitative PCR validated 60% of the genes found to be regulated in the microarray. A nuclear encoded heme-binding protein of the globin family was up-regulated upon loss of
Wolbachia. Interestingly, mitochondrial encoded subunits of respiratory chain complexes containing heme and riboflavin were also up-regulated. No change in the expression of these genes was seen in tetracycline treated
Wolbachia-free
Acanthocheilonema viteae. As
Wolbachia synthesise heme and filaria do not, we hypothesise that without the endosymbionts no functional heme-containing enzymes can be formed, leading to loss of energy metabolism which then results in up-regulation of the mitochondrial encoded subunits in an attempt to correct the deviation from homeostasis. Our results support targeting the
Wolbachia heme synthesis pathway for the discovery of new anti-filarial drugs.</description><subject>Animals</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Brugia malayi</subject><subject>DNA, Complementary - genetics</subject><subject>DNA, Complementary - metabolism</subject><subject>Doxycycline - pharmacology</subject><subject>Electron Transport - genetics</subject><subject>Electron Transport - physiology</subject><subject>Filariasis</subject><subject>Filarioidea - genetics</subject><subject>Filarioidea - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genes, Mitochondrial - genetics</subject><subject>Genes, Mitochondrial - physiology</subject><subject>Heme</subject><subject>Invertebrates</subject><subject>Life cycle. Host-agent relationship. Pathogenesis</subject><subject>Litomosoides sigmodontis</subject><subject>Microarray</subject><subject>Mitochondria</subject><subject>Molecular Sequence Data</subject><subject>Nemathelminthia. Plathelmintha</subject><subject>Nematoda</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Onchocerca volvulus</subject><subject>Protozoa</subject><subject>Symbiosis</subject><subject>Tetracycline</subject><subject>Up-Regulation</subject><subject>Wolbachia</subject><subject>Wolbachia - drug effects</subject><subject>Wolbachia - physiology</subject><subject>Wuchereria bancrofti</subject><issn>0020-7519</issn><issn>1879-0135</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU2LFDEQhoMo7uzoPxDNRTz1WOmkvy6CLLoKKx508Riqk-qZDN2dNukW9x_4s83Yo97EU6B43npDPYw9EbATIMqXx507Thhwl0MagdwBqHtsI-qqyUDI4j7bAOSQVYVoLthljEcAUUilHrKLHGSZF7XYsB8f3OzNwY82OOz5nkaKvPOBH2igzNJEo6Vx5oHi5ALOPtxxc0A3cuOHqafvCcdAfJmyQPulx5ksx26mwFO4p9n5kfuOf_F9i-bgkHfBD7xzPf4qHGlISy3FR-xBh32kx-d3y27fvvl89S67-Xj9_ur1TWaUquaMailzaDFXJOrWKCobFEKWbavaCnLbCaitrau6KSoUUojTPUpUhSpItrKWW_Zi3TsF_3WhOOvBRUN9jyP5JeoqkaVo1H-QUjaVLMsmkWolTfAxBur0FNyA4U4L0CdZ-qhXWfokS4PUSVaKPT0XLO1A9k_ot50EPD8DGA32XcDRuPiXkwCFqqvEPVu5Dr3GfUjM7afUJEHUpcqT9S17tRKUTvvNUdDROBoNWRfIzNp69--__gRi0r7s</recordid><startdate>20100815</startdate><enddate>20100815</enddate><creator>Strübing, Uta</creator><creator>Lucius, Richard</creator><creator>Hoerauf, Achim</creator><creator>Pfarr, Kenneth M.</creator><general>Elsevier Ltd</general><general>[Oxford; New York]: Elsevier Science</general><general>Elsevier</general><scope>FBQ</scope><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>7X8</scope><scope>7QL</scope><scope>C1K</scope><scope>M7N</scope></search><sort><creationdate>20100815</creationdate><title>Mitochondrial genes for heme-dependent respiratory chain complexes are up-regulated after depletion of Wolbachia from filarial nematodes</title><author>Strübing, Uta ; Lucius, Richard ; Hoerauf, Achim ; Pfarr, Kenneth M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c447t-e83320ba24e18bc4e69a1136bb4b702df108dd878957a131118796a4545e3b383</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Anti-Bacterial Agents - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Brugia malayi</topic><topic>DNA, Complementary - genetics</topic><topic>DNA, Complementary - metabolism</topic><topic>Doxycycline - pharmacology</topic><topic>Electron Transport - genetics</topic><topic>Electron Transport - physiology</topic><topic>Filariasis</topic><topic>Filarioidea - genetics</topic><topic>Filarioidea - metabolism</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genes, Mitochondrial - genetics</topic><topic>Genes, Mitochondrial - physiology</topic><topic>Heme</topic><topic>Invertebrates</topic><topic>Life cycle. Host-agent relationship. Pathogenesis</topic><topic>Litomosoides sigmodontis</topic><topic>Microarray</topic><topic>Mitochondria</topic><topic>Molecular Sequence Data</topic><topic>Nemathelminthia. Plathelmintha</topic><topic>Nematoda</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Onchocerca volvulus</topic><topic>Protozoa</topic><topic>Symbiosis</topic><topic>Tetracycline</topic><topic>Up-Regulation</topic><topic>Wolbachia</topic><topic>Wolbachia - drug effects</topic><topic>Wolbachia - physiology</topic><topic>Wuchereria bancrofti</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Strübing, Uta</creatorcontrib><creatorcontrib>Lucius, Richard</creatorcontrib><creatorcontrib>Hoerauf, Achim</creatorcontrib><creatorcontrib>Pfarr, Kenneth M.</creatorcontrib><collection>AGRIS</collection><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>MEDLINE - Academic</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><jtitle>International journal for parasitology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Strübing, Uta</au><au>Lucius, Richard</au><au>Hoerauf, Achim</au><au>Pfarr, Kenneth M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mitochondrial genes for heme-dependent respiratory chain complexes are up-regulated after depletion of Wolbachia from filarial nematodes</atitle><jtitle>International journal for parasitology</jtitle><addtitle>Int J Parasitol</addtitle><date>2010-08-15</date><risdate>2010</risdate><volume>40</volume><issue>10</issue><spage>1193</spage><epage>1202</epage><pages>1193-1202</pages><issn>0020-7519</issn><eissn>1879-0135</eissn><coden>IJPYBT</coden><abstract>The filarial nematodes
Brugia malayi,
Wuchereria bancrofti and
Onchocerca volvulus cause elephantiasis or dermatitis and blindness resulting in severe morbidity. Annually, 1.3 billion people are at risk of infection. Targeting the essential
Wolbachia endobacteria of filarial nematodes with doxycycline has proven to be an effective therapy resulting in a block in embryogenesis, worm development and macrofilaricidal effects. However, doxycycline is contraindicated for a large portion of the at risk population. To identify new targets for anti-wolbachial therapy, understanding the molecular basis of the
Wolbachia–filaria symbiosis is required. Using the
B. malayi microarray we identified differentially expressed genes in the rodent filaria
Litomosoides sigmodontis after depletion of
Wolbachia which might have a role in symbiosis. The microarray data were filtered for regulated genes with a false discovery rate <5% and a ⩾2-fold-change. Most of the genes were differentially expressed at day 36 of tetracycline treatment, when 99.8% of
Wolbachia were depleted. Several classes of genes were affected, including genes for translation, transcription, folding/sorting of proteins, motility, structure and metabolic and signalling pathways. Quantitative PCR validated 60% of the genes found to be regulated in the microarray. A nuclear encoded heme-binding protein of the globin family was up-regulated upon loss of
Wolbachia. Interestingly, mitochondrial encoded subunits of respiratory chain complexes containing heme and riboflavin were also up-regulated. No change in the expression of these genes was seen in tetracycline treated
Wolbachia-free
Acanthocheilonema viteae. As
Wolbachia synthesise heme and filaria do not, we hypothesise that without the endosymbionts no functional heme-containing enzymes can be formed, leading to loss of energy metabolism which then results in up-regulation of the mitochondrial encoded subunits in an attempt to correct the deviation from homeostasis. Our results support targeting the
Wolbachia heme synthesis pathway for the discovery of new anti-filarial drugs.</abstract><cop>Kidlington</cop><pub>Elsevier Ltd</pub><pmid>20362581</pmid><doi>10.1016/j.ijpara.2010.03.004</doi><tpages>10</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | International journal for parasitology, 2010-08, Vol.40 (10), p.1193-1202 |
| issn | 0020-7519 1879-0135 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_754561948 |
| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Animals Anti-Bacterial Agents - pharmacology Biological and medical sciences Brugia malayi DNA, Complementary - genetics DNA, Complementary - metabolism Doxycycline - pharmacology Electron Transport - genetics Electron Transport - physiology Filariasis Filarioidea - genetics Filarioidea - metabolism Fundamental and applied biological sciences. Psychology Genes, Mitochondrial - genetics Genes, Mitochondrial - physiology Heme Invertebrates Life cycle. Host-agent relationship. Pathogenesis Litomosoides sigmodontis Microarray Mitochondria Molecular Sequence Data Nemathelminthia. Plathelmintha Nematoda Oligonucleotide Array Sequence Analysis Onchocerca volvulus Protozoa Symbiosis Tetracycline Up-Regulation Wolbachia Wolbachia - drug effects Wolbachia - physiology Wuchereria bancrofti |
| title | Mitochondrial genes for heme-dependent respiratory chain complexes are up-regulated after depletion of Wolbachia from filarial nematodes |
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