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Background  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.    Methods and Findings  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.    Conclusions  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.

Microarray-Based Analysis of Differential Gene Expression between Infective and Noninfective Larvae of Strongyloides stercoralis