Bacillus anthracis is the causative agent of anthrax, and the spore form of the bacterium represents the infectious particle introduced into a host. The spore is surrounded by an exosporium, a loose-fitting membrane composed of proteins and carbohydrates from which hair-like projections extend. These projections are composed mainly of BclA (Bacillus-collagen-like protein of B. anthracis). To date, exact roles of the exosporium structure and BclA protein remain undetermined. We examined differences in spore binding of wild-type Ames and a bclA mutant of B. anthracis to bronchial epithelial cells as well as to the following other epithelial cells: A549, CHO, and Caco-2 cells; the IMR-90 fibroblast line; and human umbilical vein vascular endothelium cells. The binding of wild-type Ames spores to bronchial epithelial cells appeared to be a dose-dependent, receptor-ligand-mediated event. There were similar findings for the bclA mutant, with an additional nonspecific binding component likely leading to significantly more adherence to all nonprofessional phagocytic cell types. In contrast, we detected no difference in adherence and uptake of spores by macrophages for either the wild-type Ames or the bclA mutant strain. These results suggest that one potential role of the BclA fibers may be to inhibit nonspecific interactions between B. anthracis spores with nonprofessional phagocytic cells and thus direct the spores towards uptake by macrophages during initiation of infection in mammals.Bacillus anthracis, a gram-positive, spore-forming bacillus, is the causative agent of anthrax (11,25). The spore structure of B. anthracis consists of overlapping layers called the core, cortex, coat, and exosporium (9). The central interior of a spore, known as the core, houses the chromosome. The cortex is a thick layer of peptidoglycan that surrounds the core (27), which is then further enveloped by the spore coat (1). The outermost structure of the B. anthracis spore is a loose-fitting exosporium (12). Approximately 20 exosporium-associated proteins and glycoproteins have been identified from analyses of B. anthracis and Bacillus cereus spores (4,5,29,(35)(36)(37)(38)(39). The exosporium membrane projects hair-like fibers (12) of which the major component is the BclA glycoprotein (35, 37).Fibers of the B. anthracis exosporium were once believed to be important for virulence or adherence to host cells (20). However, several studies have demonstrated that the fibers and exosporium are not necessary for full virulence of B. anthracis. Upon identifying the BclA protein, Sylvestre et al. (37) examined the effect of a bclA mutation on the virulence of the attenuated Sterne strain of B. anthracis. In this first study, when spores were administered subcutaneously to mice, no appreciable differences in virulence were observed between the parental Sterne and bclA mutant strains (37). We recently showed that by using a fully virulent strain of B. anthracis, an Ames bclA mutant retains complete virulence in mouse and guinea pig models of anthr...