Abstract
Antibiotic resistance is a major threat to human health. Since resistance to the aminoglycoside class of antibiotics is most commonly caused by enzymatic modification, we developed a high-throughput microarray platform for directly assaying resistance enzyme activity on aminoglycosides. After modification, the array can be hybridized with the therapeutic target, a bacterial rRNA A-site mimic, to study the effect that modification has on binding. Such studies will help identify important factors that contribute to high-affinity recognition of therapeutic targets and low-affinity recognition of and modification by resistance enzymes. This platform may also be useful for screening chemical libraries to discover new antibiotics that evade resistance.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adenosine Triphosphate / metabolism
-
Aminoglycosides / chemical synthesis*
-
Aminoglycosides / chemistry
-
Aminoglycosides / pharmacology*
-
Anti-Bacterial Agents / chemical synthesis
-
Anti-Bacterial Agents / chemistry
-
Anti-Bacterial Agents / pharmacology
-
Binding Sites
-
Carbohydrate Sequence
-
Drug Resistance, Bacterial*
-
Escherichia coli / metabolism
-
Kanamycin / chemical synthesis
-
Kanamycin / chemistry
-
Kanamycin / pharmacology
-
Kanamycin Kinase / metabolism
-
Microbial Sensitivity Tests / methods
-
Models, Chemical
-
Molecular Sequence Data
-
Molecular Structure
-
RNA, Ribosomal / metabolism
-
Reproducibility of Results
-
Tobramycin / chemical synthesis
-
Tobramycin / chemistry
-
Tobramycin / pharmacology
Substances
-
Aminoglycosides
-
Anti-Bacterial Agents
-
RNA, Ribosomal
-
Kanamycin
-
Adenosine Triphosphate
-
Kanamycin Kinase
-
Tobramycin