Abstract
Spores of Bacillus anthracis, the causative agent of anthrax, are known to persist in the host lungs for prolonged periods of time, however the underlying mechanism is poorly understood. In this study, we demonstrated that BclA, a major surface protein of B. anthracis spores, mediated direct binding of complement factor H (CFH) to spores. The surface bound CFH retained its regulatory cofactor activity resulting in C3 degradation and inhibition of downstream complement activation. By comparing results from wild type C57BL/6 mice and complement deficient mice, we further showed that BclA significantly contributed to spore persistence in the mouse lungs and dampened antibody responses to spores in a complement C3-dependent manner. In addition, prior exposure to BclA deletion spores (ΔbclA) provided significant protection against lethal challenges by B. anthracis, whereas the isogenic parent spores did not, indicating that BclA may also impair protective immunity. These results describe for the first time an immune inhibition mechanism of B. anthracis mediated by BclA and CFH that promotes spore persistence in vivo. The findings also suggested an important role of complement in persistent infections and thus have broad implications.
Highlights
Persistent colonization of the host by microbial pathogens can cause chronic infections, which are often difficult to treat with conventional antibiotics
We discovered an immune modulatory mechanism of Bacillus anthracis mediated by the spore surface protein Bacillus collagen-like protein of anthracis (BclA)
Using mice deficient in complement components, we further showed that BclA promoted spore persistence in the mouse lungs and impaired antibody responses against spores in a complement-dependent manner
Summary
Persistent colonization of the host by microbial pathogens can cause chronic infections, which are often difficult to treat with conventional antibiotics. It is recognized that persistent infection is a unique phase often involving specific virulence factors and pathogenic mechanisms [1]. Identifying and understanding these persistent mechanisms is key to developing new strategies to more effectively combat chronic infections. One of the characteristic features of inhalational anthrax is the ability of spores to persist in the host lungs for prolonged periods of time [2,3,4,5,6,7]. Incubation periods of up to 43 days have been observed in humans [6] This led to the 60-day antibiotic regimen recommended by the Centers for Disease Control and Prevention for people with pulmonary exposure to B. anthracis spores [7]
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