A collagen‐like surface glycoprotein is a structural component of the <i>Bacillus anthracis</i> exosporium

Sylvestre, Patricia; Couture‐Tosi, Evelyne; Mock, Michèle

doi:10.1046/j.1365-2958.2000.03000.x

Cited by 307 publications

(422 citation statements)

References 66 publications

Supporting

Mentioning

405

Contrasting

Unclassified

Order By: Relevance

“…Collagen-like proteins are rare in prokaryotic organisms, and those described seem to be located on microbial surfaces and are often involved in adherence (22,23). Because BclA forms the outermost component of the spore (18,24), we hypothesized that it would play a role in spore-host interactions. To study this possibility, the effect of the ⌬bclA mutation on cellular adherence and uptake was determined.…”

Section: Bcla Protein Restricts Internalization Of B Anthracis Sporementioning

confidence: 99%

The integrin Mac-1 (CR3) mediates internalization and directsBacillus anthracisspores into professional phagocytes

Oliva¹,

Swiecki²,

Griguer³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

113

View full text Add to dashboard Cite

Anthrax, a disease caused by Bacillus anthracis, affects animals and humans. Because the inert spore is the infectious form of the organism that first contacts the potential host, the interaction between the host and spore exosporium is vital to the initiation of disease. Here, we demonstrate that the integrin Mac-1 is essential for the recognition of the major exosporium protein BclA by phagocytic cells. Expression of Mac-1, but not p150/95, in CHO cells markedly enhanced infection with Sterne strain of B. anthracis spores (WT spores). Conversely, CD11b ؊/؊ macrophages demonstrated a significant decrease in spore uptake when compared with macrophages from normal C57BL/6 mice. However, when CD11b ؊/؊ macrophages were infected with ⌬bclA spores, spore ingestion was no different from their C57BL/6 counterparts. ⌬bclA spores were also efficiently internalized by all CHO cell lines tested, independently of Mac-1 expression. Taken together, these results show that there is an alternative Mac-1-independent pathway involved in spore uptake that is unmasked only in the absence of BclA. Survival studies, using C57BL/6 and CD11b ؊/؊ mice, revealed that CD11b ؊/؊ mice are more resistant to infection with WT but not ⌬bclA spores. Our experiments also show that ⌬bclA spores are more virulent than WT spores in C57BL/6 and A/J mice. Overall, our data indicate that the Mac-1/BclA interaction may play a major role in B. anthracis pathogenesis by promoting spore uptake by professional phagocytes and subsequent access to a favorable niche for transport, germination, and outgrowth in lymphoid tissues.A nthrax, a disease affecting humans and livestock, is caused by the spore-forming encapsulated Gram-positive bacterium Bacillus anthracis. This organism is a National Institute of Allergy and Infectious Diseases category A priority pathogen because of its lethality and significant potential for misuse (1). The severity of anthrax pathogenicity depends on the route of uptake. After inhalation, the most toxic route, B. anthracis spores are believed to be phagocytosed by alveolar macrophages in the lungs of infected hosts (2). During or after the migration of infected macrophages to regional lymph nodes, B. anthracis spores germinate and become encapsulated toxin-producing bacteria (2). The transformation from a dormant spore to a fully vegetative bacterium is a critical initial step in anthrax pathogenicity (3).Recently, remarkable strides have been made in the understanding of the structure and biological activities of B. anthracis virulence factors (4, 5). To date, however, neither a receptor on host cells to facilitate spore uptake nor a spore ligand for such a hypothetical receptor have been identified.In this study, we show that a Mac-1-dependent pathway facilitates the attachment and subsequent uptake of B. anthracis spores. This obligate Mac-1 interaction is mediated by the collagen-like glycoprotein BclA, which forms a hair-like nap in the outermost (i.e., exosporium) layer of the spore, and represents a mechanism that directs s...

show abstract

Section: Bcla Protein Restricts Internalization Of B Anthracis Sporementioning

confidence: 99%

The integrin Mac-1 (CR3) mediates internalization and directsBacillus anthracisspores into professional phagocytes

Oliva¹,

Swiecki²,

Griguer³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

113

View full text Add to dashboard Cite

show abstract

“…The spore may bind to entirely different structures from the vegetative cell and requires further investigation. The exosporium is a hexagonal lattice with filamentous appendages and glycoproteins (Fox et al, 2003;Mock & Fouet, 2001;Sylvestre et al, 2002) that may provide a mechanism for spore attachment to host cells prior to macrophage internalization.…”

Section: Oligosaccharide Specificity In Relation To Bacterial Adhesinsmentioning

confidence: 99%

Common oligosaccharide moieties inhibit the adherence of typical and atypical respiratory pathogens

Thomas

Brooks

2004

Journal of Medical Microbiology

View full text Add to dashboard Cite

Intervention in bacterial adhesion to host cells is a novel method of overcoming current problems associated with antibiotic resistance. Antibiotic-resistant strains of bacteria that cause respiratory tract infections are a problem in hospitals and could be used in bioterrorist attacks. A range of bacterial species was demonstrated to attach to an alveolar epithelial (A549) cell line. In all cases, cell surface oligosaccharides were important in attachment, demonstrated by reduced adhesion when A549 cells were pre-treated with tunicamycin. Bacillus anthracis and Yersinia pestis displayed a restricted tropism for oligosaccharides compared to the environmental, opportunistic pathogens, Pseudomonas aeruginosa, Burkholderia cenocepacia, Burkholderia pseudomallei and Legionella pneumophila. The compound with the greatest anti-adhesion activity was p-nitrophenol. Other generic attachment inhibitors included the polymeric saccharides (dextran and heparin), GalNAcâ1-4Gal, GalNAcâ1-3Gal, Galâ1-4GlcNAc and Galâ1-3GlcNAc. Burkholderia pseudomallei attachment was particularly susceptible to oligosaccharide inhibition. Combinations of such compounds may serve as a novel generic therapeutics for respiratory tract infections. INTRODUCTIONThe development of antibiotic resistance amongst pathogenic bacteria is a frequent occurrence and of great concern for public health. This problem is associated with many bacteria that cause community-and hospital-acquired pneumonia such as Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa and Burkholderia cenocepacia (Lister, 2000;Lynch, 2001;Spencer, 1995;Tan, 2003). Problems with antibiotic resistance can also extend to those bacteria that could be used in bioterrorism. It is likely that such bacterial threat agents would be delivered by the aerosol route resulting in respiratory presentation of the disease (Cieslak & Eitzen, 2000;Leggiadro, 2000). Given the ease of natural acquisition of antibiotic resistance genes and genetic manipulation, it is prudent to research therapeutic alternatives to antibiotics.Attachment to cell surfaces is one of the key steps in bacterial pathogenesis, often involving oligosaccharides located on the host cell surface and bacterial adhesins (Karlsson et al., 1992;Ofek & Sharon, 1990). The terminal di-or trisaccharide units of these oligosaccharides may be used to inhibit these interactions, preventing attachment and hence disease (Zopf & Roth, 1996). The theory has been proven in vitro with a range of bacterial species. For example, lacto-N-neotetraose and asialoganglioside-GM1 (asialo-GM1) inhibit attachment of S. pneumoniae to alveolar epithelial cells (Tong et al., 1999). Similarly 3-sialyllactose inhibits Helicobacter pylori attachment to gastric epithelial cells . Asialoganglioside-GM1 and -GM2 are used as receptors by a number of respiratory pathogens, which specifically bind their terminal GalNAcâ1-3Gal and GalNAcâ1-4Gal moieties (Krivan et al., 1988a(Krivan et al., , b, 1991. The principle has also been proven to be valid in vivo...

show abstract

“…In some species, including Bacillus anthracis and its close relatives Bacillus cereus and B. thuringiensis, the spore is enclosed in an additional relatively poorly studied external structure known as the exosporium (11)(12)(13). The exosporium does not directly abut the coat.…”

mentioning

confidence: 99%

The dynamic spore

Driks

2003

Proc. Natl. Acad. Sci. U.S.A.

104

102

View full text Add to dashboard Cite

A collagen‐like surface glycoprotein is a structural component of the Bacillus anthracis exosporium

Cited by 307 publications

References 66 publications

The integrin Mac-1 (CR3) mediates internalization and directsBacillus anthracisspores into professional phagocytes

The integrin Mac-1 (CR3) mediates internalization and directsBacillus anthracisspores into professional phagocytes

Common oligosaccharide moieties inhibit the adherence of typical and atypical respiratory pathogens

The dynamic spore

Contact Info

Product

Resources

About