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Enteric bacteria increase the defenses against oxidative stress in Entamoeba histolytica

ABSTRACT: Characterization of the human microbiota is providing new insightsinto the complexity of host–parasite–bacterium relationships. Amoebiasis (an intestinal infection affecting a large proportion of the population in many countries worldwide) is caused by the amoebic parasite Entamoeba histolytica. During amoebiasis, the parasite encounters several types of stress as a result of the host’s response to infection. Given that E. histolytica phagocytises bacteria in the intestinal lumen, we hypothesized that enteric bacteria can influence the course of an amoebic infection. Hence, we used live Escherichia coli O55 as a pertinent model of the bacterial community’s contribution to amoebic responses during host- induced stress. By measuring amoebic survival, we found that live E. coli protected E. histolytica against oxidative stress (OS) but not against nitrosative stress. E. coli– associated protection is correlated with massive transcriptionalchanges in amoebic genes acquired through lateral transfer from the bacterial kingdom, including genes coding for proteinscontaining leucine-rich repeat (LRR) motifs. The transcriptome profile triggered by OS and E. coli was also observed with other enteric bacteria, including pathogens and non-pathogens. In contrast, exposure to a probiotic resulted in a different transcriptome profile. The present study shows that OS and live bacteria together modulate 84 of E. histolytica’s 137 LRR protein genes. The LRR proteins are involvedin protein-ligand and protein-protein interactions – especially in proteins that interact with bacteria as part of the innate immune response in mammals and plants, such as Toll-like receptors. The structural and functional homology of LRRs and TLRs identified here suggest that despite its old age in evolutionary terms, the protozoan E. histolytica displays key characteristics of higher eukaryotes’ innate immune systems. We conclude that components of innate immunity existed in the common ancestor of plants and animals

ORGANISM(S): Entamoeba histolytica

PROVIDER: GSE104434 | GEO | 2018/06/08

REPOSITORIES: GEO

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Project description:Entamoeba histolytica is a human pathogen, responsible for amoebic dysentery and invasive extraintestinal disease. The parasite faces several types of stress within the host, and to establish a successful infection it must generate a robust adaptive response against host defense mechanisms. In order to obtain comprehensive information of gene expression changes in E. histolytica under growth stress, we have (1) optimized the proteomics protocol to increase the protein coverage in E. histolytica, and (2) integrated proteomic data with transcriptomic analysis under the same conditions. We have applied this approach to better understand the cellular response during serum-starvation. Label-free quantitative proteomics was performed, and compared with mRNA levels based on RNA-seq data to decipher regulation at translational and transcriptional levels. Across all samples, 2344 proteins were identified, which is an improvement over the maximum recorded number in E. histolytica proteomic studies so far. A total of 127 proteins were found to be differentially expressed and associated with functions including antioxidant activity, cytoskeleton, translation, catalysis, and transport, which revealed proteomic signatures to distinguish serum-starved from normal trophozoites. Gal/GalNAc-inhibitable lectin, Lgls, Hgl3 and Igl were repeatedly identified as significantly altered in serum-stress condition. Further, integration of transcriptomic and proteomic data revealed instances of post-transcriptional regulation. Six highly expressed transcripts had low corresponding protein expression, indicating translational repression. Conversely, eleven transcripts showed much greater downregulation compared with their corresponding proteins, indicating translational induction, or increased stability of these proteins during serum stress in E. histolytica. This multi-omics approach enables more refined gene expression analysis that would not be possible at the mRNA or protein levels alone. Our study provides important data to further understand the adaptive response of E. histolytica to growth stress.

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Enteric bacteria increase the defenses against oxidative stress in Entamoeba histolytica

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