对来自泰乐菌素产生菌弗氏链霉菌的MLS耐药决定子tlrD的分子分析。

Molecular analysis of tlrD, an MLS resistance determinant from the tylosin producer, Streptomyces fradiae.

作者信息

Gandecha A R, Cundliffe E

机构信息

Department of Biochemistry, University of Leicester, UK.

出版信息

Gene. 1996 Nov 21;180(1-2):173-6. doi: 10.1016/s0378-1119(96)00448-9.

DOI:10.1016/s0378-1119(96)00448-9

PMID:8973363

Abstract

The macrolide antibiotic, tylosin (Ty), is produced by Streptomyces fradiae. Two resistance determinants (tlrA, synonym ermSF, and tlrD) conferring resistance to macrolide, lincosamide and streptogramin B type (MLS) antibiotics were previously isolated from this strain, and their products shown to methylate 23S ribosomal RNA (rRNA) at a common site, thereby rendering the ribosomes MLS resistant. However, the TlrA and TlrD proteins differ in their action; the former dimethylates, and the latter monomethylates, the target nucleotide. Here, 2.2 kb of DNA from the tylLM region of the tylosin biosynthetic gene cluster of S. fradiae has been sequenced and shown to encompass tlrD. Comparison of the sequences of tlrA and tlrD (and of their deduced products) with those of related ('erm-type') genes from other actinomycetes suggests that the combined presence of tlrA and tlrD in S. fradiae is not the result of recent gene duplication.

摘要

大环内酯类抗生素泰乐菌素（Ty）由弗氏链霉菌产生。先前已从该菌株中分离出两个赋予对大环内酯类、林可酰胺类和链阳菌素B型（MLS）抗生素抗性的抗性决定簇（tlrA，同义词ermSF和tlrD），并且已证明它们的产物在一个共同位点使23S核糖体RNA（rRNA）甲基化，从而使核糖体对MLS具有抗性。然而，TlrA和TlrD蛋白的作用不同；前者使靶核苷酸二甲基化，而后者使其单甲基化。在此，对弗氏链霉菌泰乐菌素生物合成基因簇的tylLM区域的2.2 kb DNA进行了测序，并显示其包含tlrD。将tlrA和tlrD（及其推导产物）的序列与来自其他放线菌的相关（“erm型”）基因的序列进行比较表明，弗氏链霉菌中tlrA和tlrD的共同存在不是近期基因复制的结果。