Department of Microbial Pathogenesis, Genentech, Inc., South San Francisco, California, USA.
Infect Immun. 2012 Oct;80(10):3512-20. doi: 10.1128/IAI.00686-12. Epub 2012 Jul 30.
SecA2 is an ATPase present in some pathogenic Gram-positive bacteria, is required for translocation of a limited set of proteins across the cytosolic membrane, and plays an important role in virulence in several bacteria, including mycobacteria that cause diseases such as tuberculosis and leprosy. However, the mechanisms by which SecA2 affects virulence are incompletely understood. To investigate whether SecA2 modulates host immune responses in vivo, we studied Mycobacterium marinum infection in two different hosts: an established zebrafish model and a recently described mouse model. Here we show that M. marinum ΔsecA2 was attenuated for virulence in both host species and SecA2 was needed for normal granuloma numbers and for optimal tumor necrosis factor alpha response in both zebrafish and mice. M. marinum ΔsecA2 was more sensitive to SDS and had unique protrusions from its cell envelope when examined by cryo-electron tomography, suggesting that SecA2 is important for bacterial cell wall integrity. These results provide evidence that SecA2 induces granulomas and is required for bacterial modulation of the host response because it affects the mycobacterial cell envelope.
SecA2 是一种存在于某些致病性革兰氏阳性细菌中的 ATP 酶，对于跨细胞质膜转运有限数量的蛋白质是必需的，并且在几种细菌的毒力中发挥重要作用，包括引起结核病和麻风病等疾病的分枝杆菌。然而，SecA2 影响毒力的机制尚不完全清楚。为了研究 SecA2 是否在体内调节宿主免疫反应，我们在两种不同的宿主中研究了海洋分枝杆菌感染：一个已建立的斑马鱼模型和最近描述的小鼠模型。在这里，我们表明，M. marinum ΔsecA2 在两种宿主物种中的毒力都减弱，并且 SecA2 对于正常的肉芽肿数量和在斑马鱼和小鼠中最佳的肿瘤坏死因子 alpha 反应都是必需的。用冷冻电子断层扫描检查时，M. marinum ΔsecA2 对 SDS 更敏感，并且其细胞包膜有独特的突起，表明 SecA2 对细菌细胞壁完整性很重要。这些结果提供了证据，表明 SecA2 诱导了肉芽肿，并被要求对宿主反应进行细菌调节，因为它影响了分枝杆菌的细胞包膜。
