Comparative Study of Eis-like Enzymes from Pathogenic and Nonpathogenic Bacteria.
Antibiotic resistance is a growing problem worldwide. Of particular importance is the resistance of Mycobacterium tuberculosis (Mtb) to currently available antibiotics used in the treatment of infected patients. Up-regulation of an aminoglycoside (AG) acetyltransferase, the enhanced intracellular survival (Eis) protein of Mtb (Eis_Mtb), is responsible for resistance to the second-line injectable drug kanamycin A in a number of Mtb clinical isolates. This acetyltransferase is known to modify AGs, not at a single position, as usual for this type of enzyme, but at multiple amine sites. We identified, using in silico techniques, 22 homologues from a wide variety of bacteria, that we then cloned, purified, and biochemically studied. From the selected Eis homologues, 7 showed the ability to modify AGs to various degrees and displayed both similarities and differences when compared to Eis_Mtb. In addition, an inhibitor proved to be active against all homologues tested. Our findings show that this family of acetyltransferase enzymes exists in both mycobacteria and non-mycobacteria and in both pathogenic and nonpathogenic species. The bacterial strains described herein should be monitored for rising resistance rates to AGs.
College of Pharmacy, University of Kentucky , Lexington, Kentucky 40536-0596, United States.
Keith D
KD
Green
Rachel E
RE
Pricer
Megan N
MN
Stewart
College of Pharmacy, University of Kentucky , Lexington, Kentucky 40536-0596, United States.
Sylvie
S
Garneau-Tsodikova
acetylation; aminoglycoside acetyltransferases; enzyme inhibitors; n-propionylation; sequential reactions