Heffernan Brian J, Thomason Brendan, Herring-Palmer Amy, Shaughnessy Lee, McDonald Rod, Fisher Nathan, Huffnagle Gary B, Hanna Philip
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109-0620, USA.
Infect Immun. 2006 Jul;74(7):3756-64. doi: 10.1128/IAI.00307-06.
Several models of anthrax pathogenesis suggest that early in the infectious process Bacillus anthracis endospores germinate and outgrow into vegetative bacilli within phagocytes before being released into the blood. Here, we define the respective contributions of three phospholipases C (PLCs) to the pathogenesis of B. anthracis. Genetic deletions of the PLCs were made in the Sterne 7702 background, resulting in the respective loss of their activities. The PLCs were redundant both in tissue culture and in murine models of anthrax. Deletion of all three PLC genes was required for attenuation of virulence in mice after intratracheal inoculation. This attenuation may be attributed to the inability of the PLC-null strain to grow in association with the macrophage. Complementation of these defects in both models of anthrax was achieved by expression of the PLC genes in trans. The functional redundancy between PLCs in the virulence of B. anthracis implies that their activities are important for anthrax pathogenesis.
几种炭疽发病机制模型表明，在感染过程早期，炭疽芽孢杆菌芽孢在被释放到血液之前，先在吞噬细胞内萌发并生长为营养型杆菌。在此，我们确定了三种磷脂酶C（PLCs）对炭疽芽孢杆菌发病机制的各自贡献。在Sterne 7702背景下对PLCs进行基因缺失，导致其活性分别丧失。PLCs在组织培养和炭疽小鼠模型中都是冗余的。气管内接种后，小鼠毒力减弱需要缺失所有三个PLC基因。这种毒力减弱可能归因于PLC缺失菌株无法与巨噬细胞结合生长。通过反式表达PLC基因，在两种炭疽模型中都弥补了这些缺陷。炭疽芽孢杆菌毒力中PLCs之间的功能冗余意味着它们的活性对炭疽发病机制很重要。
