Microarray-based analysis of differential gene expression between infective and noninfective larvae of Strongyloides stercoralis.

<h4>Background</h4>Differences between noninfective first-stage (L1) and infective third-stage (L3i) larvae of parasitic nematode Strongyloides stercoralis at the molecular level are relatively uncharacterized. DNA microarrays were developed and utilized for this purpose.<h4>Method...

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Autores principales: Roshan Ramanathan, Sudhir Varma, José M C Ribeiro, Timothy G Myers, Thomas J Nolan, David Abraham, James B Lok, Thomas B Nutman
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Publicado: Public Library of Science (PLoS) 2011
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spelling oai:doaj.org-article:967c5cdf2ecd4cdf916a973dd730db262021-11-18T09:13:24ZMicroarray-based analysis of differential gene expression between infective and noninfective larvae of Strongyloides stercoralis.1935-27271935-273510.1371/journal.pntd.0001039https://doaj.org/article/967c5cdf2ecd4cdf916a973dd730db262011-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21572524/?tool=EBIhttps://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735<h4>Background</h4>Differences between noninfective first-stage (L1) and infective third-stage (L3i) larvae of parasitic nematode Strongyloides stercoralis at the molecular level are relatively uncharacterized. DNA microarrays were developed and utilized for this purpose.<h4>Methods and findings</h4>Oligonucleotide hybridization probes for the array were designed to bind 3,571 putative mRNA transcripts predicted by analysis of 11,335 expressed sequence tags (ESTs) obtained as part of the Nematode EST project. RNA obtained from S. stercoralis L3i and L1 was co-hybridized to each array after labeling the individual samples with different fluorescent tags. Bioinformatic predictions of gene function were developed using a novel cDNA Annotation System software. We identified 935 differentially expressed genes (469 L3i-biased; 466 L1-biased) having two-fold expression differences or greater and microarray signals with a p value<0.01. Based on a functional analysis, L1 larvae have a larger number of genes putatively involved in transcription (p = 0.004), and L3i larvae have biased expression of putative heat shock proteins (such as hsp-90). Genes with products known to be immunoreactive in S. stercoralis-infected humans (such as SsIR and NIE) had L3i biased expression. Abundantly expressed L3i contigs of interest included S. stercoralis orthologs of cytochrome oxidase ucr 2.1 and hsp-90, which may be potential chemotherapeutic targets. The S. stercoralis ortholog of fatty acid and retinol binding protein-1, successfully used in a vaccine against Ancylostoma ceylanicum, was identified among the 25 most highly expressed L3i genes. The sperm-containing glycoprotein domain, utilized in a vaccine against the nematode Cooperia punctata, was exclusively found in L3i biased genes and may be a valuable S. stercoralis target of interest.<h4>Conclusions</h4>A new DNA microarray tool for the examination of S. stercoralis biology has been developed and provides new and valuable insights regarding differences between infective and noninfective S. stercoralis larvae. Potential therapeutic and vaccine targets were identified for further study.Roshan RamanathanSudhir VarmaJosé M C RibeiroTimothy G MyersThomas J NolanDavid AbrahamJames B LokThomas B NutmanPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 5, Iss 5, p e1039 (2011)
institution DOAJ
collection DOAJ
language EN
topic Arctic medicine. Tropical medicine
RC955-962
Public aspects of medicine
RA1-1270
spellingShingle Arctic medicine. Tropical medicine
RC955-962
Public aspects of medicine
RA1-1270
Roshan Ramanathan
Sudhir Varma
José M C Ribeiro
Timothy G Myers
Thomas J Nolan
David Abraham
James B Lok
Thomas B Nutman
Microarray-based analysis of differential gene expression between infective and noninfective larvae of Strongyloides stercoralis.
description <h4>Background</h4>Differences between noninfective first-stage (L1) and infective third-stage (L3i) larvae of parasitic nematode Strongyloides stercoralis at the molecular level are relatively uncharacterized. DNA microarrays were developed and utilized for this purpose.<h4>Methods and findings</h4>Oligonucleotide hybridization probes for the array were designed to bind 3,571 putative mRNA transcripts predicted by analysis of 11,335 expressed sequence tags (ESTs) obtained as part of the Nematode EST project. RNA obtained from S. stercoralis L3i and L1 was co-hybridized to each array after labeling the individual samples with different fluorescent tags. Bioinformatic predictions of gene function were developed using a novel cDNA Annotation System software. We identified 935 differentially expressed genes (469 L3i-biased; 466 L1-biased) having two-fold expression differences or greater and microarray signals with a p value<0.01. Based on a functional analysis, L1 larvae have a larger number of genes putatively involved in transcription (p = 0.004), and L3i larvae have biased expression of putative heat shock proteins (such as hsp-90). Genes with products known to be immunoreactive in S. stercoralis-infected humans (such as SsIR and NIE) had L3i biased expression. Abundantly expressed L3i contigs of interest included S. stercoralis orthologs of cytochrome oxidase ucr 2.1 and hsp-90, which may be potential chemotherapeutic targets. The S. stercoralis ortholog of fatty acid and retinol binding protein-1, successfully used in a vaccine against Ancylostoma ceylanicum, was identified among the 25 most highly expressed L3i genes. The sperm-containing glycoprotein domain, utilized in a vaccine against the nematode Cooperia punctata, was exclusively found in L3i biased genes and may be a valuable S. stercoralis target of interest.<h4>Conclusions</h4>A new DNA microarray tool for the examination of S. stercoralis biology has been developed and provides new and valuable insights regarding differences between infective and noninfective S. stercoralis larvae. Potential therapeutic and vaccine targets were identified for further study.
format article
author Roshan Ramanathan
Sudhir Varma
José M C Ribeiro
Timothy G Myers
Thomas J Nolan
David Abraham
James B Lok
Thomas B Nutman
author_facet Roshan Ramanathan
Sudhir Varma
José M C Ribeiro
Timothy G Myers
Thomas J Nolan
David Abraham
James B Lok
Thomas B Nutman
author_sort Roshan Ramanathan
title Microarray-based analysis of differential gene expression between infective and noninfective larvae of Strongyloides stercoralis.
title_short Microarray-based analysis of differential gene expression between infective and noninfective larvae of Strongyloides stercoralis.
title_full Microarray-based analysis of differential gene expression between infective and noninfective larvae of Strongyloides stercoralis.
title_fullStr Microarray-based analysis of differential gene expression between infective and noninfective larvae of Strongyloides stercoralis.
title_full_unstemmed Microarray-based analysis of differential gene expression between infective and noninfective larvae of Strongyloides stercoralis.
title_sort microarray-based analysis of differential gene expression between infective and noninfective larvae of strongyloides stercoralis.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/967c5cdf2ecd4cdf916a973dd730db26
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