Disney Matthew D, Barrett Olivia J
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.
Biochemistry. 2007 Oct 9;46(40):11223-30. doi: 10.1021/bi701071h. Epub 2007 Sep 15.
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.
抗生素耐药性是对人类健康的重大威胁。由于对氨基糖苷类抗生素的耐药性最常见是由酶促修饰引起的，我们开发了一种高通量微阵列平台，用于直接检测对氨基糖苷类抗生素的耐药酶活性。修饰后，该阵列可与治疗靶点（一种细菌rRNA A位点模拟物）杂交，以研究修饰对结合的影响。此类研究将有助于确定有助于高亲和力识别治疗靶点以及低亲和力识别耐药酶并被其修饰的重要因素。该平台还可能有助于筛选化学文库，以发现能规避耐药性的新型抗生素。
