Uropathogenic E. coli mediated ACLY dependent acetyl-CoA change control IL 8 expression

The virulence factor HlyA of Uropathogenic Escherichia coli (UPEC) could modulate host cell metabolism and inhibits NF-κB signaling pathway. However, whether there is a link between these two processes remains elusive. Here, we demonstrated UPEC could suppress metabolic enzyme ATP citrate lyase (ACLY) that resulted into histone deacetylation by decreasing the levels of acetyl-CoA. The level of histone acetylation was rescued supplementation of acetate. Furthermore, using H3 Lysine9 acetylation (H3K9ac) immunoprecipitation coupled next generation sequencing (ChIP-seq), we found that UPEC cause site specific regulation of H3K9ac which correlates with the expression of pro-inflammatory cytokines and chemokines. To be more specific, the expression of pro-inflammatory cytokines and chemokines like IL 8, CXCL2, and IL-1α are suppressed by UPEC mediated decreasing of H3K9ac at TSS-promoter region. Thus, this study established that UPEC manipulate host cell metabolism to impact histone acetylation at specific loci, correlating with cytokines and chemokines expression, as a means to inhibit NF-κB signaling. 15 samples: 3 replicates CTRL, 3 replicates HDM 2h, 3 replicates HDM 4h, replicates UPEC 2h, 3 replicates UPEC 4h