Comparative Study of Eis-like Enzymes from Pathogenic and Nonpathogenic Bacteria

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• 作者：Keith D. Green ; Rachel E. Pricer ; Megan N. Stewart ; Sylvie Garneau-Tsodikova
• 刊名：ACS Infectious Diseases
• 出版年：2015
• 出版时间：June 12, 2015
• 年：2015
• 卷：1
• 期：6
• 页码：272-283
• 全文大小：640K
• ISSN：2373-8227

文摘

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.