An aminoglycoside microarray platform for directly monitoring and studying antibiotic resistance.
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.
Disney
Matthew D
MD
Department of Chemistry and The Center for Excellence in Bioinformatics and Life Sciences, University at Buffalo, 657 Natural Sciences Complex, Buffalo, New York 14260, USA. mddisney@buffalo.edu
Barrett
Olivia J
OJ
D000255:Adenosine Triphosphate / Q000378:metabolism; D000617:Aminoglycosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D002240:Carbohydrate Sequence; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000378:metabolism; D007612:Kanamycin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D019868:Kanamycin Kinase / Q000378:metabolism; D008826:Microbial Sensitivity Tests / Q000379:methods; D008956:Models, Chemical; D008969:Molecular Sequence Data; D015394:Molecular Structure; D012335:RNA, Ribosomal / Q000378:metabolism; D015203:Reproducibility of Results; D014031:Tobramycin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D012335:RNA, Ribosomal; D007612:Kanamycin; D000255:Adenosine Triphosphate; D019868:Kanamycin Kinase; D014031:Tobramycin