Aminoglycoside antibiotic resistance conferred by Hpa2 of MDR : an unusual adaptation of a common histone acetyltransferase.

Antibiotic-resistant bacteria pose the greatest threat to human health. Among the list of such bacteria released by WHO, carbapenem-resistant , for which almost no treatment exists, tops the list. is one of the most troublesome ESKAPE pathogens and mechanisms that have facilitated its rise as a successful pathogen are not well studied. Efforts in this direction have resulted in the identification of Hpa2-, an uncharacterized histone acetyltransferase enzyme of GNAT superfamily. Here, we show that Hpa2- confers resistance against aminoglycoside antibiotics using DH5α strains in which gene is expressed. Resistivity for aminoglycoside antibiotics is demonstrated with the help of CLSI-2010 and KB tests. Isothermal titration calorimetry, MALDI and acetylation assays indicate that conferred resistance is an outcome of evolved antibiotic acetylation capacity in this. Hpa2 is known to acetylate nuclear molecules; however, here it is found to cross its boundary and participate in other functions. An array of biochemical and biophysical techniques were also used to study this protein, which demonstrates that Hpa2 is intrinsically oligomeric in nature, exists primarily as a dimer and its interface is mainly stabilized by hydrophobic interactions. Our work demonstrates an evolved survival strategy by and provides insights into the mechanism that facilitates it to rise as a successful pathogen.