Braunstein Miriam, Espinosa Benjamin J, Chan John, Belisle John T, Jacobs William R
Howard Hughes Medical Institute, Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Mol Microbiol. 2003 Apr;48(2):453-64. doi: 10.1046/j.1365-2958.2003.03438.x.
Tuberculosis remains a severe worldwide health threat. A thorough understanding of Mycobacterium tuberculosis pathogenesis will facilitate the development of new treatments for tuberculosis. Numerous bacterial pathogens possess specialized protein secretion systems that are dedicated to the export of virulence factors. Mycobacterium tuberculosis is part of a developing group of pathogenic bacteria that share the uncommon property of possessing two secA genes (secA1 and secA2). In mycobacteria, SecA1 is the essential 'housekeeping' SecA protein whereas SecA2 is an accessory secretion factor. Here we demonstrate that SecA2 contributes to the pathogenesis of M. tuberculosis. A deletion of the secA2 gene in M. tuberculosis attenuates the virulence of the organism in mice. By comparing the profile of proteins secreted by wild-type M. tuberculosis and the DeltasecA2 mutant, we identified superoxide dismutase A (SodA) as a protein dependent on SecA2 for secretion. SodA lacks a classical signal sequence for protein export. Our data suggests that SecA2-dependent export is a new type of secretion pathway that is part of a virulence mechanism of M. tuberculosis to elude the oxidative attack of macrophages.
结核病仍然是全球严重的健康威胁。深入了解结核分枝杆菌的发病机制将有助于开发新的结核病治疗方法。许多细菌病原体拥有专门的蛋白质分泌系统，专门用于输出毒力因子。结核分枝杆菌是一群正在发展的致病细菌的一部分，这些细菌具有拥有两个secA基因（secA1和secA2）这一不寻常的特性。在分枝杆菌中，SecA1是必需的“管家”SecA蛋白，而SecA2是一种辅助分泌因子。在此，我们证明SecA2有助于结核分枝杆菌的发病机制。结核分枝杆菌中secA2基因的缺失会减弱该生物体在小鼠中的毒力。通过比较野生型结核分枝杆菌和DeltasecA2突变体分泌的蛋白质谱，我们确定超氧化物歧化酶A（SodA）是一种依赖SecA2进行分泌的蛋白质。SodA缺乏用于蛋白质输出的经典信号序列。我们的数据表明，SecA2依赖性输出是一种新型的分泌途径，是结核分枝杆菌逃避巨噬细胞氧化攻击的毒力机制的一部分。
