The Threat of Biological Terrorism: A Public Health and Infection Control Reality

Leggiadro, Robert J.

doi:10.1086/501700

Cited by 45 publications

(15 citation statements)

References 15 publications

(10 reference statements)

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“…It cannot be discounted that expression of the capsule would alter the inhibition profile of this bacterium. Similarly, it should be recognized that in the event of pneumonic disease, such as would occur in the case of bioterrorism, initial interactions with the host cell would involve the B. anthracis spore prior to germination (Cieslak & Eitzen, 2000;Leggiadro, 2000). The spore may bind to entirely different structures from the vegetative cell and requires further investigation.…”

Section: Oligosaccharide Specificity In Relation To Bacterial Adhesinsmentioning

confidence: 99%

“…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.…”

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confidence: 99%

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

Thomas

Brooks

2004

Journal of Medical Microbiology

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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...

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Section: Oligosaccharide Specificity In Relation To Bacterial Adhesinsmentioning

confidence: 99%

mentioning

confidence: 99%

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

Thomas

Brooks

2004

Journal of Medical Microbiology

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“…burnetii has a high degree of resistance to physical and chemical agents (38,46) and can withstand desiccation and remain infectious in contaminated soils for years (53). Due to the highly infectious nature of C. burnetii and its hardiness under adverse environmental conditions, the organism is considered a category B agent by the Centers for Disease Control and Prevention and has been included in the list of weapons of mass destruction likely to be used in bioterrorism and biological warfare (13,23). Weaponization and mass production of this organism have already been accomplished (43,48), reinforcing the need for a safe, efficacious vaccine that could be used to protect populations at risk following a deliberate or natural outbreak.…”

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confidence: 99%

Clinical and Pathologic Changes in a Guinea Pig Aerosol Challenge Model of Acute Q Fever

et al. 2006

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Acute Q fever is a zoonotic disease caused by the obligate intracellular bacterium Coxiella burnetii and can manifest as a flu-like illness, pneumonia, or hepatitis. A need exists in Q fever research for animal models mimicking both the typical route of infection (inhalation) and the clinical illness seen in human cases of Q fever. A guinea pig aerosol challenge model was developed using C. burnetii Nine Mile phase I (RSA 493), administered using a specialized chamber designed to deliver droplet nuclei directly to the alveolar spaces. Guinea pigs were given 10 1 to 10 6 organisms and evaluated for 28 days postinfection. Clinical signs included fever, weight loss, respiratory difficulty, and death, with the degree and duration of response corresponding to the dose of organism delivered. Histopathologic evaluation of the lungs of animals infected with a high dose showed coalescing panleukocytic bronchointerstitial pneumonia at 7 days postinfection that resolved to multifocal lymphohistiocytic interstitial pneumonia by 28 days. Guinea pigs receiving a killed whole-cell vaccine prior to challenge with the highest dose of C. burnetii were protected against lethal infection and did not develop fever. Clinical signs and pathological changes noted for these guinea pigs were comparable to those seen in human acute Q fever, making this an accurate and valuable animal model of human disease.

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“…fare threat, its biologic activity makes it an increasingly useful therapeutic agent (2,3). Produced as a single polypeptide chain by the bacterium Clostridium botulinum, BoNT/A (150 kDa) is subsequently cleaved into two functional subunits held together by a disulfide bond.…”

mentioning

confidence: 99%

Botulinum Neurotoxin A Activity Is Dependent upon the Presence of Specific Gangliosides in Neuroblastoma Cells Expressing Synaptotagmin I

Yowler

Kensinger

Schengrund

2002

Journal of Biological Chemistry

127

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Botulinum neurotoxin A (BoNT/A) is the deadliest of all known biological substances. Although its toxicity makes BoNT/A a biological warfare threat, its biologic activity makes it an increasingly useful therapeutic agent for the treatment of muscular disorders. However, almost 200 years after its discovery, the neuronal cell components required for the activity of this deadly toxin have not been unequivocally identified. In this work, neuroblastoma cells expressing synaptotagmin I, a protein shown to be bound by BoNT/A, were used to determine whether specific gangliosides were necessary for BoNT/A activity as measured by synaptosomal-associated protein of 25 kDa (SNAP-25) cleavage. Ganglioside GT1b was found to support BoNT/A activity significantly more effectively than GD1a, which was far more effective than GM1 when added to ganglioside-deficient murine cholinergic Neuro 2a or to human adrenergic SK-N-SH neuroblastoma cells. Whereas both cell lines expressed synaptotagmin I, SNAP-25 cleavage was not observed in the absence of complex gangliosides. These results indicate that 1) gangliosides are required for BoNT/A activity, 2) synaptotagmin I in the absence of gangliosides does not support BoNT/A activity, and 3) Neuro 2a cells are an efficient model system for studying the biological activity of BoNT/A.

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The Threat of Biological Terrorism: A Public Health and Infection Control Reality

Cited by 45 publications

References 15 publications

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

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

Clinical and Pathologic Changes in a Guinea Pig Aerosol Challenge Model of Acute Q Fever

Botulinum Neurotoxin A Activity Is Dependent upon the Presence of Specific Gangliosides in Neuroblastoma Cells Expressing Synaptotagmin I

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