Mukhtar Tariq A, Koteva Kalinka P, Wright Gerard D
Antimicrobial Research Centre, Department of Biochemistry and Biomedical Sciences, McMaster University, 1200 Main Street, West Hamilton, Ontario, L8N 3Z5, Canada.
Chem Biol. 2005 Feb;12(2):229-35. doi: 10.1016/j.chembiol.2004.12.009.
Streptogramin antibiotics are comprised of two distinct chemical components: the type A polyketides and the type B cyclic depsipeptides. Clinical resistance to the type B streptogramins can occur via enzymatic degradation catalyzed by the lyase Vgb or by target modification through the action of Erm ribosomal RNA methyltransferases. We have prepared through chemical and chemo-enzymatic approaches a series of chimeric antibiotics composed of elements of type B streptogramins and the membrane-active antibiotic tyrocidine that evade these resistance mechanisms. These new compounds show broad antibiotic activity against gram-positive bacteria including a number of important pathogens, and chimeras appear to function by a mechanism that is distinct from their parent antibiotics. These results allow for the development of a brand new class of antibiotics with the ability to evade type B streptogramin-resistance mechanisms.
A型聚酮化合物和B型环缩肽。对B型链阳性菌素的临床耐药性可通过裂合酶Vgb催化的酶促降解或通过Erm核糖体RNA甲基转移酶的作用进行靶点修饰而产生。我们通过化学和化学酶法制备了一系列由B型链阳性菌素和膜活性抗生素短杆菌肽的成分组成的嵌合抗生素，这些抗生素能够规避这些耐药机制。这些新化合物对革兰氏阳性菌具有广泛的抗菌活性，包括许多重要病原体，并且嵌合体似乎通过一种与其亲本抗生素不同的机制发挥作用。这些结果为开发一类全新的、能够规避B型链阳性菌素耐药机制的抗生素提供了可能。
