RRC ID 71540
Author Mishra P, Beura S, Sikder S, Dhal AK, Vasudevan M, Roy M, Rakshit J, Budhwar R, Kundu TK, Modak R.
Title vp1524, a Vibrio parahaemolyticus NAD +-dependent deacetylase, regulates host response during infection by induction of host histone deacetylation.
Journal J Biochem
Abstract Gram-negative intracellular pathogen Vibrio parahaemolyticus manifests its infection through a series of effector proteins released into the host via the type III secretion system. Most of these effector proteins alter signalling pathways of the host to facilitate survival and proliferation of bacteria inside host cells. Here, we report V. parahaemolyticus (serotype O3:K6) infection-induced histone deacetylation in host intestinal epithelial cells, particularly deacetylation of H3K9, H3K56, H3K18 and H4K16 residues. We found a putative NAD+-dependent deacetylase, vp1524 (vpCobB) of V. parahaemolyticus, was overexpressed during infection. Biochemical assays revealed that Vp1524 is a functional NAD+-dependent Sir2 family deacetylase in vitro, which was capable of deacetylating acetylated histones. Furthermore, we observed that vp1524 is expressed and localized to the nuclear periphery of the host cells during infection. Consequently, Vp1524 translocated to nuclear compartments of transfected cells, deacetylated histones, specifically causing deacetylation of those residues (K56, K16, K18) associated with V. parahaemolyticus infection. This infection induced deacetylation resulted in transcriptional repression of several host genes involved in epigenetic regulation, immune response, autophagy etc. Thus, our study shows that a V. parahaemolyticus lysine deacetylase Vp1524 is secreted inside the host cells during infection, modulating host gene expression through histone deacetylation.
Volume 171(6)
Pages 673-693
Published 2022-5-27
DOI 10.1093/jb/mvac027
PII 6552324
PMID 35325168
MeSH Epigenesis, Genetic Group III Histone Deacetylases / metabolism* Histones / metabolism Immunity NAD / genetics NAD / metabolism Vibrio parahaemolyticus* / genetics Vibrio parahaemolyticus* / metabolism
Pathogenic bacteria