Abstract
inhibits autophagy to promote its survival in host cells. However, the molecular mechanisms by which
inhibits autophagy are poorly understood. Here, we report a previously unknown mechanism in which
phosphoribosyltransferase (
PRT) inhibits autophagy in an mTOR, negative regulator of autophagy, independent manner by inducing histone hypermethylation (H3K9me2/3) at the
and
promoters by activating p38-MAPK- and EHMT2 methyltransferase-dependent signaling pathways. Additionally, we find that
PRT induces EZH2 methyltransferase-dependent H3K27me3 hypermethylation and reduces histone acetylation modifications (H3K9ac and H3K27ac) by upregulating histone deacetylase 3 to inhibit autophagy. In summary, this is the first demonstration that
inhibits autophagy by inducing histone hypermethylation in autophagy-related genes to promote intracellular bacterial survival.