aminoglycosidemodifying

Aminoglycoside-modifying enzymes (AMEs) are a diverse group of bacterial enzymes that inactivate aminoglycoside antibiotics by chemically modifying the drug molecule. This enzymatic alteration prevents the antibiotic from binding effectively to the bacterial 30S ribosomal subunit, thereby conferring resistance. AMEs are among the most common mechanisms of acquired resistance to aminoglycosides in clinical bacteria.

AMEs are classified into three main types based on the chemical reaction they catalyze: acetylation by acetyltransferases (AACs), phosphorylation by phosphotransferases (APHs), and nucleotidylation (adenylylation) by nucleotidyltransferases (ANTs). Acetyltransferases transfer an acetyl group to amino sites on the aminoglycoside, phosphotransferases add a phosphate group to hydroxyl groups, and nucleotidyltransferases attach a nucleotide (usually AMP) to hydroxyl groups. Each enzyme family has substrate preferences, and combinations of enzymes can broaden resistance across aminoglycoside drugs such as gentamicin, tobramycin, amikacin, kanamycin, and neomycin.

Genetic context and spread: AMEs are frequently encoded on plasmids, transposons, or integrons, facilitating horizontal transfer between bacteria. This mobility contributes to rapid dissemination in hospital and community settings, often alongside other resistance determinants such as beta-lactamases. Specific gene families include acetyltransferases (aac), phosphotransferases (aph), and nucleotidyltransferases (ant); individual variants determine the exact spectrum of resistance observed in a given isolate.

Clinical significance: AMEs reduce the efficacy of aminoglycoside therapy, potentially limiting treatment options for serious infections. They are typically detected by phenotypic susceptibility testing or molecular methods such as PCR or sequencing targeting common AME genes. Management relies on antibiotic susceptibility profiles and may involve using other antibiotic classes or combination therapy, guided by stewardship principles.