Biological weapons

Bossi, Philippe; Garín, Daniel; Guihot, Amélie; Gay, Frédérick; Crance, Jean‐Marc; Debord, T.; Autran, Brigitte; Bricaire, F.

doi:10.1007/s00018-006-6308-z

Cited by 58 publications

(20 citation statements)

References 43 publications

(135 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The most prominent is the infection by spores of Bacillus anthracis which can cause various forms of anthrax disease (Dixon et al, 1999). Moreover, environmental stability and ease of production were the main reasons why spores of Bacillus anthracis have been used as bioweapons (Pohanka and Kuca, 2010) and still are considered as a relevant threat (Lane et al, 2001;Bossi et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Dormant Bacillus spores protect their DNA in crystalline nucleoids against environmental stress

Dittmann

Hong-mei

Grabenbauer

et al. 2015

Journal of Structural Biology

View full text Add to dashboard Cite

Bacterial spores of the genera Bacillus and Clostridium are extremely resistant against desiccation, heat and radiation and involved in the spread and pathogenicity of health relevant species such as Bacillus anthracis (anthrax) or Clostridium botulinum. While the resistance of spores is very well documented, underlying mechanisms are not fully understood. In this study we show, by cryo-electron microscopy of vitreous sections and particular resin thin section electron microscopy, that dormant Bacillus spores possess highly ordered crystalline core structures, which contain the DNA, but only if small acid soluble proteins (SASPs) are present. We found those core structures in spores of all Bacillus species investigated, including spores of anthrax. Similar core structures were detected in Geobacillus and Clostridium species which suggest that highly ordered, at least partially crystalline core regions represent a general feature of bacterial endospores. The crystalline core structures disintegrate in a period during spore germination, when resistance against most stresses is lost. Our results suggest that the DNA is tightly packed into a crystalline nucleoid by binding SASPs, which stabilizes DNA fibrils and protects them against modification. Thus, the crystalline nucleoid seems to be the structural and functional correlate for the remarkable stability of the DNA in bacterial endospores.

show abstract

Section: Introductionmentioning

confidence: 99%

Dormant Bacillus spores protect their DNA in crystalline nucleoids against environmental stress

Dittmann

Hong-mei

Grabenbauer

et al. 2015

Journal of Structural Biology

View full text Add to dashboard Cite

show abstract

“…Of these, the respiratory route is the most deadly, and the most likely route of infection by weaponized F . tularensis [17]. After inhalation, patients typically show signs of systemic illness, which may be accompanied by immediate signs of respiratory disease and can result in death in 30–60% of cases if left untreated [18–21].…”

Section: Introductionmentioning

confidence: 99%

Border Patrol Gone Awry: Lung NKT Cell Activation by Francisella tularensis Exacerbates Tularemia-Like Disease

et al. 2015

View full text Add to dashboard Cite

The respiratory mucosa is a major site for pathogen invasion and, hence, a site requiring constant immune surveillance. The type I, semi-invariant natural killer T (NKT) cells are enriched within the lung vasculature. Despite optimal positioning, the role of NKT cells in respiratory infectious diseases remains poorly understood. Hence, we assessed their function in a murine model of pulmonary tularemia—because tularemia is a sepsis-like proinflammatory disease and NKT cells are known to control the cellular and humoral responses underlying sepsis. Here we show for the first time that respiratory infection with Francisella tularensis live vaccine strain resulted in rapid accumulation of NKT cells within the lung interstitium. Activated NKT cells produced interferon-γ and promoted both local and systemic proinflammatory responses. Consistent with these results, NKT cell-deficient mice showed reduced inflammatory cytokine and chemokine response yet they survived the infection better than their wild type counterparts. Strikingly, NKT cell-deficient mice had increased lymphocytic infiltration in the lungs that organized into tertiary lymphoid structures resembling induced bronchus-associated lymphoid tissue (iBALT) at the peak of infection. Thus, NKT cell activation by F. tularensis infection hampers iBALT formation and promotes a systemic proinflammatory response, which exacerbates severe pulmonary tularemia-like disease in mice.

show abstract

“…The threat of smallpox has reemerged, due to the potential use of variola virus as a biological weapon for bioterrorism (Breman and Henderson, 1998; Peters, 2002; Bossi et al, 2006; Kman and Nelson, 2008). Therefore, smallpox virus vaccination using live vaccinia virus has increased in response to this perceived threat (Fulginiti et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of imiquimod for topical treatment of vaccinia virus cutaneous infections in immunosuppressed hairless mice

et al. 2011

View full text Add to dashboard Cite

Imiquimod is an immune response modifier prescribed as a topical medication for a number of viral and neoplastic conditions. We evaluated the antiviral activity of imiquimod against vaccinia virus (WR strain) cutaneous infections in immunosuppressed (with cyclophosphamide) hairless mice when administered after virus exposure. Primary lesions progressed in severity, satellite lesions developed, and infection eventually killed the mice. Once daily topical treatment with 1% imiquimod cream for three, four, or five days were compared to twice daily topical treatment with 1% cidofovir cream for seven days. Survival time of mice in all treated groups was significantly prolonged compared to placebo controls. The mean day of death for the placebo group, three-day imiquimod, four day imiquimod, five-day imiquimod, and cidofovir groups were 15.5, 20.0, 20.5, 19.5, and 20.5 days post-infection, respectively. All treatment groups showed significant reductions in primary lesion size and in the number of satellite lesions. The cidofovir and 4-day imiquimod treatments delayed the appearance of lung virus titers by 3 and 6 days, respectively, although cutaneous lesion and snout virus titers were not as affected by treatment. Benefits in survival and lesion reduction were observed when imiquimod treatment was delayed from 24, 48 and 72 hours post-infection. However, increasing the treatment dose of imiquimod from 1% to 5% led to a significant decrease in antiviral efficacy. These results demonstrate the protective effects of topically administered imiquimod against a disseminated vaccinia virus infection in this mouse model.

show abstract

Biological weapons

Cited by 58 publications

References 43 publications

Dormant Bacillus spores protect their DNA in crystalline nucleoids against environmental stress

Dormant Bacillus spores protect their DNA in crystalline nucleoids against environmental stress

Border Patrol Gone Awry: Lung NKT Cell Activation by Francisella tularensis Exacerbates Tularemia-Like Disease

Evaluation of imiquimod for topical treatment of vaccinia virus cutaneous infections in immunosuppressed hairless mice

Contact Info

Product

Resources

About