The two-component regulatory system mtrAB is required for morphotypic multidrug resistance in Mycobacterium avium
The two-component regulatory system mtrAB is required for morphotypic multidrug resistance in Mycobacterium avium
复制标题
DOI：
10.1128/aac.50.2.461-468.2006
复制
发表时间：
2006-02-01
影响因子：
4.9
通讯作者：
Behr, MA
中科院分区：
文献类型：
--
作者：
Cangelosi, GA;Do, JS;Behr, MA
机会性病原体鸟分枝杆菌复合体 (MAC) 的临床分离株在含有脂蛋白染色剂刚果红的琼脂平板上经历红色和白色菌落形态类型之间的可逆转换。与同基因的红色对应物相比，白色形态变体的毒性更强，对多种抗生素更具抵抗力。该报告表明，红白转换以及 MAC 的其他形态转换都需要二元调节系统 mtrAB。从形态典型的白色亲本克隆中分离出在组氨酸蛋白激酶基因 mtrB 中插入转座子的突变体。该突变体类似于天然存在的红色形态变体，因为它用刚果红染色，对多种抗生素敏感，并且可以被荧光 DNA 染色剂渗透。然而，它与红色变体的不同之处在于它不能转变为白色或透明的形态类型，并且它不能在巨噬细胞样细胞内存活。与克隆的野生型 mtrB 基因的反式互补使突变体恢复了形成不可渗透、耐药的白色和透明变体的能力。定量逆转录酶 PCR 显示，mtrB 是细胞表面 Mce 蛋白正常表达所必需的，其中一些蛋白在红白转换中上调。结果表明，mtrAB 具有调节分枝杆菌细胞壁的组成和通透性的功能，并在 MAC 的可逆集落类型转换中发挥作用。
Clinical isolates of the opportunistic pathogen Mycobacterium avium complex (MAC) undergo a reversible switch between red and white colony morphotypes on agar plates containing the lipoprotein stain Congo red. Compared to their isogenic red counterparts, white morphotypic variants are more virulent and more resistant to multiple antibiotics. This report shows that the two-component regulatory system mtrAB is required for the red-to-white switch as well as for other morphotypic switches of MAC. A mutant with a transposon insertion in the histidine protein kinase gene mtrB was isolated from a morphotypically white parent clone. The mutant resembled a naturally occurring red morphotypic variant in that it stained with Congo red, was sensitive to multiple antibiotics, and was permeable by a fluorescent DNA stain. However, it differed from a red variant in that it could not switch to the white or transparent morphotype, and it could not survive intracellularly within macrophage-like cells. Transcomplementation with a cloned wild-type mtrB gene restored to the mutant the ability to form impermeable, drug-resistant white and transparent variants. Quantitative reverse transcriptase PCR showed that mtrB was required for the normal expression of cell surface Mce proteins, some of which are up-regulated in the red-to-white switch. The results indicate that mtrAB functions in regulating the composition and permeability of mycobacterial cell walls and plays a role in the reversible colony type switches of MAC.