Abstract
Enterotoxigenic Escherichia coli (ETEC) that express F4 (K88) fimbriae are the principal microorganisms responsible for bacterial diarrhea in neonatal and pre-weaning piglets. To better understand the molecular effects of ETEC F4ab/ac infection, we performed a genome-wide comparison of the changes in DNA methylation and gene expression in ETEC F4ab/ac infected porcine intestinal epithelial cells. We characterized the pattern of changes in methylation and found 3297 and 1593 differentially methylated regions in cells infected with F4ab and F4ac, respectively. Moreover, 606 and 780 differentially expressed genes (DEGs) in ETEC F4ab and F4ac infected cells were detected and these genes were highly enriched in immune/defense response related pathways. Integrative analysis identified 27 and 10 genes showing inverse correlations between promoter methylation and expression with ETEC F4ab/ac infection. Altered DNA methylation and expression of various genes suggested their roles and potential functional interactions upon ETEC F4ab/ac infection. Further functional analyses revealed that three DEGs (S100A9, SGO1, and ESPL1) in F4ab infected cells and three DEGs (MAP3K21, PAK6, and MPZL1) in F4ac infected cells are likely involved in the host cells response to ETEC infection. Our data provides further insight into the epigenetic and transcriptomic alterations of ETEC F4ab/ac infected porcine intestinal epithelial cells, and may advance the identification of biomarkers and drug targets for predicting susceptibility to and controlling ETEC F4ab/ac induced diarrhea.
Highlights
Enterotoxigenic Escherichia coli (ETEC) with F4 (K88) fimbriae is the leading cause of diarrhea in neonatal and pre-weaning piglets, resulting in levels of illness and mortality that have become a major economic burden to the pig farming industry worldwide (Wang W. et al, 2019)
Using a sliding-window peak-finding algorithm provided by NimbleScan v2.6 (Roche-NimbleGen), a total of 46,940 methylated enrichment peaks (EPs) were identified from the nine samples, of which 14,805 (31.54%) were in the ETEC F4ab infected samples, 16,336 (34.80%) in the ETEC F4ac infected samples, and 15,799 (33.66%) in the uninfected control samples (Table S1)
We found that compared to the uninfected cells, the ETEC F4ab infected cells had fewer methylated EPs in high CpG density promoter (HCP), while the ETEC F4ac infected cells had slightly more methylated EPs in HCPs, this held true for promoter CpG islands (CGIs) as well (Figures 2C,D)
Summary
Enterotoxigenic Escherichia coli (ETEC) with F4 (K88) fimbriae is the leading cause of diarrhea in neonatal and pre-weaning piglets, resulting in levels of illness and mortality that have become a major economic burden to the pig farming industry worldwide (Wang W. et al, 2019). The “a” is a common antigenic factor, whereas “b”, “c”, and “d” represent specific epitopes (Sinha et al, 2019) The fimbriae of these three variants share similarities in their structures including the major. Combined Analysis of DNA Methylome and Transcriptome subunit, FaeG, and several minor subunits (FaeF, FaeH, FaeC, probably FaeI, and FaeJ), all of which are controlled by a single gene cluster (Xia et al, 2015). Of these three variants, F4ab and F4ac are most commonly associated with ETEC-induced diarrhea (Nguyen et al, 2017). Identifying control strategies for ETEC F4ab/ac-induced piglet diarrhea is highly important for promoting the development of swine industry worldwide
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