Polyamine acetylation and substrate-induced oligomeric states in histone acetyltransferase of multiple drug resistant Acinetobacter baumannii

Histone acetyltransferase (Hpa2) is an unusual acetyltransferase, with a wide range of substrates; including histones, polyamines and aminoglycosides antibiotic. Hpa2 belongs to GNAT superfamily and GNATs are well known for the formation of homo-oligomers. However, the reason behind their oligomerization remained unexplored. Here, oligomeric states of Hpa2 were explored, to understand the functional significance of oligomerization. Biochemical analysis suggests that Hpa2 exists as dimer in solution and self-assembles into tetramer in the spermine, spermidine and kanamycin bound form. Stability analysis with denaturants concludes that homo-oligomerization of Hpa2 relies on bound substrate and not on experimental conditions. Homo-oligomerization in Hpa2 depicts direct correlation with its polyamine acetylating capacity. This correlation and in silico model structures suggest that oligomerization of Hpa2 is associated with the hastening of acetylation process. Interestingly, polyamine acetylation down regulates biofilms formation in E. coli BL21/Hpa2-transformants cells. Therefore, we propose that Hpa2 manipulates survival strategies of the bacterium via polyamines and antibiotics acetylation. •Hpa2 acetylates a wide range of substrates including histone, polyamines and aminoglycosides antibiotic.•Hpa2 adopts different homo-oligomeric states depending on the bound substrates.•Hpa2 homo-oligomerization depicts direct correlation with its polyamine acetylating capacity.•Biofilms assay results reveal that polyamine acetylation indeed plays an essential role in biofilm formation.