Abstract

BackgroundAs an obligate intracellular parasite, Apicomplexa interacts with the host in the special living environment, competing for energy and nutrients from the host cells by manipulating the host metabolism. Previous studies of host-parasite interaction mainly focused on using cellular and biochemical methods to investigate molecular functions in metabolic pathways of parasite infected hosts. Computational approaches taking advantage of high-throughput biological data and topology of metabolic pathways have a great potential in revealing the details and mechanism of parasites-to-host interactions. A new analytical method was designed in this work to study host-parasite interactions in human cells infected with Plasmodium falciparum and Cryptosporidium parvum.ResultsWe introduced a new method that analyzes the host metabolic pathways in divided parts: host specific subpathways and host-parasite common subpathways. Upon analysis on gene expression data from cells infected by Plasmodium falciparum or Cryptosporidium parvum, we found: (i) six host-parasite common subpathways and four host specific subpathways were significantly altered in plasmodium infected human cells; (ii) plasmodium utilized fatty acid biosynthesis and elongation, and Pantothenate and CoA biosynthesis to obtain nutrients from host environment; (iii) in Cryptosporidium parvum infected cells, most of the host-parasite common enzymes were down-regulated, whereas the host specific enzymes up-regulated; (iv) the down-regulation of common subpathways in host cells might be caused by competition for the substrates and up-regulation of host specific subpathways may be stimulated by parasite infection.ConclusionResults demonstrated a significantly coordinated expression pattern between the two groups of subpathways. The method helped expose the impact of parasite infection on host cell metabolism, which was previously concealed in the pathway enrichment analysis. Our approach revealed detailed subpathways and metabolic information are important to the symbiosis in two kinds of the apicomplex parasites, and highlighted its significance in research and understanding of parasite-host interactions.

Highlights

  • As an obligate intracellular parasite, Apicomplexa interacts with the host in the special living environment, competing for energy and nutrients from the host cells by manipulating the host metabolism

  • Using false discovery rate (FDR) less than 0.01, we found a group of genes whose expressions were significantly altered when comparing the epithelial blood expression profile from acutely infected patient with from uninfected people

  • The result indicates two pathways (KEGG ID hsa00062: Fatty acid elongation in mitochondria, hsa00410: beta-Alanine metabolism) were significantly altered (FDR

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Summary

Introduction

As an obligate intracellular parasite, Apicomplexa interacts with the host in the special living environment, competing for energy and nutrients from the host cells by manipulating the host metabolism. Previous studies of host-parasite interaction mainly focused on using cellular and biochemical methods to investigate molecular functions in metabolic pathways of parasite infected hosts. Our study is focused on a type of special protozoan, apicomplexa, which interacts with its host via its unique apical organelles, apicolast This kind of parasite has a complex life cycle. After attachment and orientation on the erythrocyte surface, apicomplexa produce the small endocytic vacuole which accommodates the parasite in the feeding stage [9] This organelle is vital for the nutrient obtaining, reproducing, and other aspects of the parasite. The biological pathways that were involved in the nourishing relationship between host and parasite were analyzed to reveal the parasite-host interactions in greater details

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