Open AccessBacillus anthracis protease InhA regulates BslA‐mediated adhesion in human endothelial cells
Author(s) -
Tonry Jessica H.,
McNichol Beth A.,
Ramarao Nalini,
Chertow Daniel S.,
Kim Kwang Sik,
Stibitz Scott,
Schneewind Olaf,
Kashanchi Fatah,
Bailey Charles L.,
Popov Serguei,
Chung MyungChul
Publication year - 2012
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2012.01791.x
Subject(s) - biology , inha , bacillus anthracis , protease , microbiology and biotechnology , adhesion , bacteria , enzyme , biochemistry , genetics , mycobacterium tuberculosis , tuberculosis , chemistry , organic chemistry , medicine , pathology
Summary To achieve widespread dissemination in the host, Bacillus anthracis cells regulate their attachment to host endothelium during infection. Previous studies identified BslA ( B acillus anthracis S ‐ l ayer Protein A ), a virulence factor of B. anthracis , as necessary and sufficient for adhesion of vegetative cells to human endothelial cells. While some factors have been identified, bacteria‐specific contributions to BslA mediated adhesion remain unclear. Using the attenuated vaccine Sterne 7702 strain of B. anthracis , we tested the hypothesis that InhA (immune inhibitor A), a B. anthracis protease, regulates BslA levels affecting the bacteria's ability to bind to endothelium. To test this, a combination of inhA mutant and complementation analysis in adhesion and invasion assays, Western blot and InhA inhibitor assays were employed. Results show InhA downregulates BslA activity reducing B. anthracis adhesion and invasion in human brain endothelial cells. BslA protein levels in ΔinhA bacteria were significantly higher than wild‐type and complemented strains showing InhA levels and BslA expression are inversely related. BslA was sensitive to purified InhA degradation in a concentration‐ and time‐dependent manner. Taken together these data support the role of InhA regulation of BslA‐mediated vegetative cell adhesion and invasion.