In vitro gene silencing of independent phosphoglycerate mutase (iPGM) in the filarial parasite Brugia malayi
Identifieur interne : 003982 ( Main/Exploration ); précédent : 003981; suivant : 003983In vitro gene silencing of independent phosphoglycerate mutase (iPGM) in the filarial parasite Brugia malayi
Auteurs : Prashant Kumar Singh [Inde] ; Susheela Kushwaha [Inde] ; Shahab Mohd [Inde] ; Manisha Pathak [Inde] ; Shailja Misra-Bhattacharya [Inde]Source :
- Infectious Diseases of Poverty [ 2049-9957 ] ; 2013.
Abstract
The phosphoglycerate mutase (PGM) enzyme catalyzes the interconversion of 2- and 3-phosphoglycerate in the glycolytic /gluconeogenic pathways that are present in the majority of cellular organisms. They can be classified as cofactor-dependent PGM (dPGM) or cofactor-independent PGM (iPGM). Vertebrates, yeasts, and many bacteria have only dPGM, while higher plants, nematodes, archaea, and many other bacteria have only iPGM. A small number of bacteria, including
The
The findings clearly suggest that iPGM is essential for both larval and adult stages of
Url:
DOI: 10.1186/2049-9957-2-5
PubMed: 23849829
PubMed Central: 3707094
Affiliations:
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gene silencing of independent phosphoglycerate mutase (iPGM) in the filarial parasite <italic>Brugia malayi</italic>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main"><italic>In vitro</italic>
gene silencing of independent phosphoglycerate mutase (iPGM) in the filarial parasite <italic>Brugia malayi</italic>
</title>
<author><name sortKey="Singh, Prashant Kumar" sort="Singh, Prashant Kumar" uniqKey="Singh P" first="Prashant Kumar" last="Singh">Prashant Kumar Singh</name>
<affiliation wicri:level="1"><nlm:aff id="I1">Division of Parasitology, CSIR-Central Drug Research Institute, B.S. 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, UP, 226021, India</nlm:aff>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Division of Parasitology, CSIR-Central Drug Research Institute, B.S. 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, UP, 226021</wicri:regionArea>
<wicri:noRegion>226021</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kushwaha, Susheela" sort="Kushwaha, Susheela" uniqKey="Kushwaha S" first="Susheela" last="Kushwaha">Susheela Kushwaha</name>
<affiliation wicri:level="1"><nlm:aff id="I1">Division of Parasitology, CSIR-Central Drug Research Institute, B.S. 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, UP, 226021, India</nlm:aff>
<country xml:lang="fr">Inde</country>
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<author><name sortKey="Mohd, Shahab" sort="Mohd, Shahab" uniqKey="Mohd S" first="Shahab" last="Mohd">Shahab Mohd</name>
<affiliation wicri:level="1"><nlm:aff id="I1">Division of Parasitology, CSIR-Central Drug Research Institute, B.S. 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, UP, 226021, India</nlm:aff>
<country xml:lang="fr">Inde</country>
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<author><name sortKey="Pathak, Manisha" sort="Pathak, Manisha" uniqKey="Pathak M" first="Manisha" last="Pathak">Manisha Pathak</name>
<affiliation wicri:level="1"><nlm:aff id="I1">Division of Parasitology, CSIR-Central Drug Research Institute, B.S. 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, UP, 226021, India</nlm:aff>
<country xml:lang="fr">Inde</country>
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<author><name sortKey="Misra Bhattacharya, Shailja" sort="Misra Bhattacharya, Shailja" uniqKey="Misra Bhattacharya S" first="Shailja" last="Misra-Bhattacharya">Shailja Misra-Bhattacharya</name>
<affiliation wicri:level="1"><nlm:aff id="I1">Division of Parasitology, CSIR-Central Drug Research Institute, B.S. 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, UP, 226021, India</nlm:aff>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Division of Parasitology, CSIR-Central Drug Research Institute, B.S. 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, UP, 226021</wicri:regionArea>
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<series><title level="j">Infectious Diseases of Poverty</title>
<idno type="eISSN">2049-9957</idno>
<imprint><date when="2013">2013</date>
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<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p>The phosphoglycerate mutase (PGM) enzyme catalyzes the interconversion of 2- and 3-phosphoglycerate in the glycolytic /gluconeogenic pathways that are present in the majority of cellular organisms. They can be classified as cofactor-dependent PGM (dPGM) or cofactor-independent PGM (iPGM). Vertebrates, yeasts, and many bacteria have only dPGM, while higher plants, nematodes, archaea, and many other bacteria have only iPGM. A small number of bacteria, including <italic>Escherichia coli</italic>
and certain archaea and protozoa, contain both forms. The silencing of <italic>ipgm</italic>
in <italic>Caenorhabditis elegans</italic>
(<italic>C. elegans</italic>
) has demonstrated the importance of this enzyme in parasite viability and, therefore, its potential as an anthelmintic drug target. In this study, the role of the <italic>Brugia malayi</italic>
(<italic>B. malayi</italic>
) ipgm in parasite viability, microfilaria release, embryogenesis, and <italic>in vivo</italic>
development of infective larvae post-gene silencing was explored by applying ribonucleic acid (RNA) interference studies.</p>
</sec>
<sec><title>Results</title>
<p>The <italic>in vitro ipgm</italic>
gene silencing by small interfering RNA (siRNA) leads to severe phenotypic deformities in the intrauterine developmental stages of female worms with a drastic reduction (~90%) in the motility of adult parasites and a significantly reduced (80%) release of microfilariae (mf) by female worms <italic>in vitro</italic>
. Almost half of the <italic>in vitro-</italic>
treated infective L3 displayed sluggish movement. The <italic>in vivo</italic>
survival and development of siRNA-treated infective larvae (L3) was investigated in the peritoneal cavity of jirds where a ~45% reduction in adult worm establishment was observed.</p>
</sec>
<sec><title>Conclusion</title>
<p>The findings clearly suggest that iPGM is essential for both larval and adult stages of <italic>B. malayi</italic>
parasite and that it plays a pivotal role in female worm embryogenesis. The results thus validate the Bm-iPGM as a putative anti-filarial drug target.</p>
</sec>
</div>
</front>
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<author><name sortKey="Assmann, Sm" uniqKey="Assmann S">SM Assmann</name>
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<author><name sortKey="Haanstra, Jr" uniqKey="Haanstra J">JR Haanstra</name>
</author>
<author><name sortKey="Hannaert, V" uniqKey="Hannaert V">V Hannaert</name>
</author>
<author><name sortKey="Van Roy, J" uniqKey="Van Roy J">J Van-Roy</name>
</author>
<author><name sortKey="Opperdoes, Fr" uniqKey="Opperdoes F">FR Opperdoes</name>
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<author><name sortKey="Bakker, Bm" uniqKey="Bakker B">BM Bakker</name>
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<author><name sortKey="Michels, Pa" uniqKey="Michels P">PA Michels</name>
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<biblStruct><analytic><author><name sortKey="Leyva Vazquez, Ma" uniqKey="Leyva Vazquez M">MA Leyva-Vazquez</name>
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<author><name sortKey="Setlow, P" uniqKey="Setlow P">P Setlow</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Morris, Vl" uniqKey="Morris V">VL Morris</name>
</author>
<author><name sortKey="Jackson, Dp" uniqKey="Jackson D">DP Jackson</name>
</author>
<author><name sortKey="Grattan, M" uniqKey="Grattan M">M Grattan</name>
</author>
<author><name sortKey="Ainsworth, T" uniqKey="Ainsworth T">T Ainsworth</name>
</author>
<author><name sortKey="Cuppels, Da" uniqKey="Cuppels D">DA Cuppels</name>
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<affiliations><list><country><li>Inde</li>
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</list>
<tree><country name="Inde"><noRegion><name sortKey="Singh, Prashant Kumar" sort="Singh, Prashant Kumar" uniqKey="Singh P" first="Prashant Kumar" last="Singh">Prashant Kumar Singh</name>
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<name sortKey="Kushwaha, Susheela" sort="Kushwaha, Susheela" uniqKey="Kushwaha S" first="Susheela" last="Kushwaha">Susheela Kushwaha</name>
<name sortKey="Misra Bhattacharya, Shailja" sort="Misra Bhattacharya, Shailja" uniqKey="Misra Bhattacharya S" first="Shailja" last="Misra-Bhattacharya">Shailja Misra-Bhattacharya</name>
<name sortKey="Mohd, Shahab" sort="Mohd, Shahab" uniqKey="Mohd S" first="Shahab" last="Mohd">Shahab Mohd</name>
<name sortKey="Pathak, Manisha" sort="Pathak, Manisha" uniqKey="Pathak M" first="Manisha" last="Pathak">Manisha Pathak</name>
</country>
</tree>
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</record>
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