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

Area of Science:

• Microbiology and Molecular Biology
• Drug Resistance Mechanisms
• Biochemistry

Background:

• Antibiotic resistance is a significant global health challenge, particularly concerning Mycobacterium tuberculosis (Mtb) infections.
• Enhanced intracellular survival (Eis) protein in Mtb confers resistance to kanamycin A by acetylating aminoglycosides at multiple sites.

Purpose of the Study:

• To investigate the prevalence and characteristics of Eis homologues in various bacterial species.
• To understand the biochemical activity of these homologues against aminoglycoside antibiotics.
• To identify potential therapeutic targets for combating aminoglycoside resistance.

Main Methods:

• In silico identification of 22 Eis homologues across diverse bacterial species.
• Cloning, purification, and biochemical characterization of selected Eis homologues.
• Testing the activity of a known inhibitor against identified homologues.

Main Results:

• Seven out of the 22 identified Eis homologues demonstrated aminoglycoside-modifying activity.
• These homologues exhibited both similarities and differences in their enzymatic properties compared to Eis_Mtb.
• A single inhibitor was effective against all tested Eis homologues, indicating a conserved mechanism.

Conclusions:

• The Eis family of acetyltransferases is present in a wide range of bacteria, including mycobacteria and non-mycobacteria, and in both pathogenic and nonpathogenic species.
• The broad distribution of these enzymes suggests a widespread mechanism for aminoglycoside resistance.
• Continuous monitoring of bacterial strains for increasing aminoglycoside resistance rates is crucial.