Chauhan Ashwini, Madiraju Murty V V S, Fol Marek, Lofton Hava, Maloney Erin, Reynolds Robert, Rajagopalan Malini
Biomedical Research, The University of Texas Health Center at Tyler, Tyler, TX 75708-3154, USA.
J Bacteriol. 2006 Mar;188(5):1856-65. doi: 10.1128/JB.188.5.1856-1865.2006.
FtsZ, a bacterial homolog of tubulin, forms a structural element called the FtsZ ring (Z ring) at the predivisional midcell site and sets up a scaffold for the assembly of other cell division proteins. The genetic aspects of FtsZ-catalyzed cell division and its assembly dynamics in Mycobacterium tuberculosis are unknown. Here, with an M. tuberculosis strain containing FtsZ(TB) tagged with green fluorescent protein as the sole source of FtsZ, we examined FtsZ structures under various growth conditions. We found that midcell Z rings are present in approximately 11% of actively growing cells, suggesting that the low frequency of Z rings is reflective of their slow growth rate. Next, we showed that SRI-3072, a reported FtsZ(TB) inhibitor, disrupted Z-ring assembly and inhibited cell division and growth of M. tuberculosis. We also showed that M. tuberculosis cells grown in macrophages are filamentous and that only a small fraction had midcell Z rings. The majority of filamentous cells contained nonring, spiral-like FtsZ structures along their entire length. The levels of FtsZ in bacteria grown in macrophages or in broth were comparable, suggesting that Z-ring formation at midcell sites was compromised during intracellular growth. Our results suggest that the intraphagosomal milieu alters the expression of M. tuberculosis genes affecting Z-ring formation and thereby cell division.
FtsZ是微管蛋白的细菌同源物，在细胞分裂前的细胞中部位点形成一种称为FtsZ环（Z环）的结构元件，并为其他细胞分裂蛋白的组装搭建支架。结核分枝杆菌中FtsZ催化的细胞分裂及其组装动力学的遗传学方面尚不清楚。在此，我们以一株含有绿色荧光蛋白标记的FtsZ（TB）作为FtsZ唯一来源的结核分枝杆菌菌株，研究了不同生长条件下的FtsZ结构。我们发现，在约11%的活跃生长细胞中存在细胞中部Z环，这表明Z环的低频率反映了它们缓慢的生长速率。接下来，我们表明，一种已报道的FtsZ（TB）抑制剂SRI-3072破坏了Z环组装，并抑制了结核分枝杆菌的细胞分裂和生长。我们还表明，在巨噬细胞中生长的结核分枝杆菌细胞呈丝状，只有一小部分有细胞中部Z环。大多数丝状细胞在其整个长度上含有非环状、螺旋状的FtsZ结构。在巨噬细胞或肉汤中生长的细菌中FtsZ的水平相当，这表明在细胞内生长期间，细胞中部位点的Z环形成受到损害。我们的结果表明，吞噬体内环境改变了影响Z环形成从而影响细胞分裂的结核分枝杆菌基因的表达。
