Aminoglycoside Modifying Enzymes

By M. Ramírez, M. Tolmasky. Drug resistance updates, 2010

915 citations recorded by the source corpus.

Aminoglycosides have been an essential component of the armamentarium in the treatment of life-threatening infections. Unfortunately, their efficacy has been reduced by the surge and dissemination of resistance. In some cases the levels of resistance reached the point that rendered them virtually useless. Among many known mechanisms of resistance to aminoglycosides, enzymatic modification is the most prevalent in the clinical setting. Aminoglycoside modifying enzymes catalyze the modification at different −OH or −NH2 groups of the 2-deoxystreptamine nucleus or the sugar moieties and can be nucleotidyltranferases, phosphotransferases, or acetyltransferases. The number of aminoglycoside modifying enzymes identified to date as well as the genetic environments where the coding genes are located is impressive and there is virtually no bacteria that is unable to support enzymatic resistance to aminoglycosides. Aside from the development of new aminoglycosides refractory to as many as possible modifying enzymes there are currently two main strategies being pursued to overcome the action of aminoglycoside modifying enzymes. Their successful development would extend the useful life of existing antibiotics that have proven effective in the treatment of infections. These strategies consist of the development of inhibitors of the enzymatic action or of the expression of the modifying enzymes.

Subfields: Ecology, Genetics, Molecular Medicine

View Paper: https://www.semanticscholar.org/paper/550d17aa58c5f01f422aea6694a969577eb6e6db

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Citations in the corpus

• Antibiotic Resistance Mechanisms in Bacteria: Relationships Between Resistance Determinants of Antibiotic Producers, Environmental Bacteria, and Clinical Pathogens (2018, background): “, 2004; Ramirez and Tolmasky, 2010), and a detailed nomenclature has been developed (Ramirez and Tolmasky, 2010; Becker and Cooper, 2013).”
• Antimicrobial Resistance in ESKAPE Pathogens (2020, background): “While comprehensive analyses of global AAC epidemiology remain relatively scarce, recent investigations conducted in the United States, Europe, and Asia indicate that Gram-negative ESKAPE pathogens most frequently encode AAC(3) and AAC(6=) enzymes, which collectively confer resistance to gentamicin,”
• Acquired Antibiotic Resistance Genes: An Overview (2011, background): “These proteins are classified into three major classes according to the type of modification: AAC (acetyltransferases),ANT (nucleotidyltransferases or adenyltransferases), APH (phosphotransferases; Shaw et al., 1993;Wright and Thompson, 1999; Magnet and Blanchard, 2005; Wright, 2005; Ramirez and Tol”
• Antibiotic resistance in Staphylococcus aureus. Current status and future prospects (2017, background): “Recent reviews describe the diversity of aminoglycoside modifying enzymes (Wright 1999; Ramirez and Tolmasky 2010).”
• Pseudomonas aeruginosa: pathogenesis, virulence factors, antibiotic resistance, interaction with host, technology advances and emerging therapeutics (2022, background): “The currently known aminoglycoside modifying enzymes utilize three common mechanisms: aminoglycoside phosphotransferase (APH), aminoglycoside acetyltransferase (AAC), and aminoglycoside nucleotide transferase (ANT).(249,250) These enzymes trigger the resistance of different antibiotics through vario”