New protein fold revealed by a 1.65 A resolution crystal structure of Francisella tularensis pathogenicity island protein IglC

Francisella tularensis is a highly infectious Gram-negative intracellular pathogen that causes the fulminating disease tularemia and is considered to be a potential bioweapon. F. tularensis pathogenicity island proteins play a key role in modulating phagosome biogenesis and subsequent bacterial escape into the cytoplasm of macrophages. The 23 kDa pathogenicity island protein IglC is essential for the survival and proliferation of F. tularensis in macrophages. Seeking to gain some insight into its function, we determined the crystal structure of IglC at 1.65 A resolution. IglC adopts a beta-sandwich conformation that exhibits no similarity with any known protein structure.     

城市小区环境生物剂气溶胶的扩散模拟研究

目的:研究城市小区中生物剂气溶胶的扩散模拟和污染区域的划分,为反生物恐怖危害评估及应急响应提供决策依据。方法:以典型生物剂炭疽为例,利用计算流体力学中的离散相模型对小区环境中生物剂气溶胶的扩散规律进行研究;对扩散后生物剂气溶胶的数目分布进行量化分析,结合吸入式炭疽的剂量-反应模型进行污染区域的划分。结果:通过计算机模拟,得到了生物剂气溶胶在小区环境中的扩散规律及数目分布,并依据人员感染炭疽概率的不同划分出小区内的污染区域。结论:利用离散相模型和剂量-反应模型,可以对城市小区中生物剂气溶胶的扩散规律进行模拟并划分污染区域,为反生物恐怖危害评估及应急响应提供决策依据。     

Hazards,threats and risks: lessons from the past to a defensive attitude for the future

Since ever infectious diseases have been a major hazard for the armed forces in operations. Nowadays our nations are facing the threat of terrorism, including bioterrorism. This threat is much more related to the potential disorganization of the society than to the lethal effects of the agents. Biological weapons are considered more like terror weapons than like mass destruction weapons, hence the importance of preparing specific defence measures. The know-how acquired from the struggle against natural infectious diseases is a useful help to face the biological weapon threats and risks. Likewise, the defence attitude is based on three pillars: anticipating, managing, and restoring. This military as well as civilian defence attitude applies to six important functions: (1) alert, (2) detection, diagnosis and identification, (3) medical countermeasures (drugs, vaccines and sera), (4) medical care in hospital, (5) training and information, (6) research and development of dedicated technologies.     

BIRS – Bioterrorism Information Retrieval System

Bioterrorism is the intended use of pathogenic strains of microbes to widen terror in a population. There is a definite need to promote research for development of vaccines, therapeutics and diagnostic methods as a part of preparedness to any bioterror attack in the future. BIRS is an open-access database of collective information on the organisms related to bioterrorism. The architecture of database utilizes the current open-source technology viz PHP ver 5.3.19, MySQL and IIS server under windows platform for database designing. Database stores information on literature, generic- information and unique pathways of about 10 microorganisms involved in bioterrorism. This may serve as a collective repository to accelerate the drug discovery and vaccines designing process against such bioterrorist agents (microbes). The available data has been validated from various online resources and literature mining in order to provide the user with a comprehensive information system.

Availability

The database is freely available at http://www.bioterrorism.biowaves.org     

Suitability of partial 16S ribosomal RNA gene sequence analysis for the identification of dangerous bacterial pathogens

AIMS: In a bioterrorism event a rapid tool is needed to identify relevant dangerous bacteria. The aim of the study was to assess the usefulness of partial 16S rRNA gene sequence analysis and the suitability of diverse databases for identifying dangerous bacterial pathogens. METHODS AND RESULTS: For rapid identification purposes a 500-bp fragment of the 16S rRNA gene of 28 isolates comprising Bacillus anthracis, Brucella melitensis, Burkholderia mallei, Burkholderia pseudomallei, Francisella tularensis, Yersinia pestis, and eight genus-related and unrelated control strains was amplified and sequenced. The obtained sequence data were submitted to three public and two commercial sequence databases for species identification. The most frequent reason for incorrect identification was the lack of the respective 16S rRNA gene sequences in the database. CONCLUSIONS: Sequence analysis of a 500-bp 16S rDNA fragment allows the rapid identification of dangerous bacterial species. However, for discrimination of closely related species sequencing of the entire 16S rRNA gene, additional sequencing of the 23S rRNA gene or sequencing of the 16S-23S rRNA intergenic spacer is essential. SIGNIFICANCE AND IMPACT OF THE STUDY: This work provides comprehensive information on the suitability of partial 16S rDNA analysis and diverse databases for rapid and accurate identification of dangerous bacterial pathogens.     

Management of natural and bioterrorism induced pandemics

A recent approach for bioterrorism risk management calls for stricter regulations over biotechnology as a way to control subversion of technology that may be used to create a man-made pandemic. This approach is largely unworkable given the increasing pervasiveness of molecular techniques and tools throughout society. Emerging technology has provided the tools to design much deadlier pathogens but concomitantly the ability to respond to emerging pandemics to reduce mortality has also improved significantly in recent decades. In its historical context determining just how 'risky' biological weapons is an important consideration for decision making and resource allocation. Management should attempt to increase capacity, share resources, provide accurate infectious disease reporting, deliver information transparency and improve communications to help mitigate the magnitude of future pandemics.     

Finding Risk-Based Switchover Points for Response Decisions for Environmental Exposure to Bacillus anthracis

In the wake of the 2001 terrorist attacks, the use of Bacillus anthracis (anthrax) in bioterrorism attacks has emerged as a realistic concern. Thus, a contingency plan is needed to inform decision-makers about which response actions are appropriate and justified under which circumstances. This study considers the decisions: (1) to undertake prophylactic antibiotic treatment; (2) to vaccinate individuals; or (3) to decontaminate the building. While these response actions are clearly justified for highly exposed individuals, a very large number of individuals exposed to very small risks in areas outside of the immediate vicinity of the release are also likely. Our results indicate that there are non-negligible risk thresholds below which response actions produce more costs than benefits. For the base case, the thresholds range from a risk of 1 in 33 for decontamination by fumigation to 1 in 6,547 for antibiotic prophylaxis and 1 in 7,108 for vaccination. A one-way sensitivity analysis on uncertain variables indicates less than an order of magnitude change in these thresholds. Benefit–cost analysis is a useful tool for assessing tradeoffs among alternative decisions, but cannot be the sole criterion in responding to incidents because of inherent limitations.     

Medical Surveillance for Biological Terrorism Agents

The first recognition of a bioterrorist attack may be sick patients. Recognition and subsequent notification of an attack at the earliest possible moment will assist in rapidly instituting protective measures. New methods of medical surveillance can assist with rapid detection. Syndromic surveillance is the use of newly created or pre-existing databases to track the health of communities. The data can include medical and non-medical information, but typically contains non-specific indicators of health status. These systems are currently being tested and fielded in multiple locations, and nationwide systems are being developed in the United States. Retrospective and prospective analyses have demonstrated the ability of the data to detect disease outbreaks, but the systems have yet to be proven to lead to more effective interventions.     

Multiple‐reaction monitoring for multiplex detection of three bacterial toxins using liquid chromatography‐tandem mass spectrometry

Clostridium perfringens epsilon toxin, staphylococcal enterotoxin B and shiga toxin are implicated in a number of diseases and food‐borne intoxications and are considered potential agents for bioterrorism and warfare. Artificially generated aerosol is the likely mode of delivery of these for nefarious uses, potentially capable of causing mass destruction to human and animal health by inhalation of toxic bioaerosol. Multiplex and unambiguous detection of these agents is of paramount importance for emergency response in a biothreat scenario and for food safety. Multiple‐reaction monitoring (MRM) assay for simultaneous monitoring of the three toxins is reported here using reverse‐phase high‐performance liquid chromatography–electrospray ionization‐tandem mass spectrometry. Three different peptides with two fragment ions each were considered for quantification and confirmation. One of the three MRM transitions from each toxin, which exhibited the best sensitivity, was selected for multiplexing of the assay. Simulating a biothreat scenario wherein the bioaerosol is collected in 10 ml of buffer, the multiplex assay was tested with blind samples with one or more of the three toxins even in the presence of interfering Escherichia coli lysate proteins.     

Quantification of the Effects of Age on the Dose Response of Variola major in Suckling Mice

Dose-response data for Variola major (V. major), the causative agent of smallpox, were obtained from the open literature, summarized, and fitted with three dose-response models. It is known from prior outbreak experience that there is generally a difference in infectivity of the agent and its subsequent mortality depending on the age of the patient. A source of animal dose-response data were found with age delineation for the exposure group (suckling mice, intraperitoneal exposure). This delineation was used to adapt current dose-response models to include an age dependency parameter. The degree of the models' fit to the data was ascertained using maximum likelihood estimation (MLE). The effect of host age could be described quantitatively using modifications to the beta Poisson and exponential dose-response models. The modifications improvement in the accuracy of risk prediction by 72% for the beta Poisson model and 7% for the exponential model, compared to the original (unmodified) models.