Crystal structures of FolM alternative dihydrofolate reductase 1 from Brucella suis and Brucella canis

Members of the bacterial genus Brucella cause brucellosis, a zoonotic disease that affects both livestock and wildlife. Brucella are category B infectious agents that can be aerosolized for biological warfare. As part of the structural genomics studies at the Seattle Structural Genomics Center for Infectious Disease (SSGCID), FolM alternative dihydrofolate reductases 1 from Brucella suis and Brucella canis were produced and their structures are reported. The enzymes share ∼95% sequence identity but have less than 33% sequence identity to other homologues with known structure. The structures are prototypical NADPH-dependent short-chain reductases that share their highest tertiary-structural similarity with protozoan pteridine reductases, which are being investigated for rational therapeutic development.

Misunderstandings of the transmission of the Black Death to Western Europe : a critical review of De Mussis’s account

This article aims to critically review de Mussis’s report of the events at Caffa. De Mussi says in his account that Tartars catapulted their dead compatriots infected by the plague into the besieged city of Caffa in order to contaminate the Genoese defending the city and that some Genoese galleys fleeing from the city transported the disease to Western Europe. Some historians interpret his report of Tartars catapulting plague-infected bodies as an act of biological warfare, and others do not trust his account as a reliable historical record, while some works rely on his account, even though they do not interpret it as evidence of biological warfare. This article tries to determine whether his account is true or not, and explain historical contexts in which it was made. De Mussi was not an eye-witness of the war between the Tartars and the Genoese in the years of 1343 to 1437 in Caffa, contrary to some historians’ arguments that he was present there during the war. In addition, he understands and explains the disease from a religious perspective as does most of his contemporary Christians, believing that the disease was God's punishment for the sins of human beings. His account of the Tartars catapulting their compatriot’s bodies may derive from his fear and hostility against the Tartars, thinking that they were devils from hell and pagans to be annihilated. For de Mussi, the Genoese may have been greedy merchants who were providing Muslims with slaves and enforcing their military forces. Therefore, he thought that the Tartars and the Genoese were sinners that spread the disease, and that God punished their arrogance. His pathological knowledge of the disease was not accurate and very limited. His medical explanation was based on humoral theory and Miasma theory that Christians and Muslims in the Mediterranean World shared. De Mussi's account that Caffa was a principal starting point for the disease to spread to Western Europe is not sufficiently supported by other contemporary documents. Byzantine chronicles and Villani's chronicle consider not Caffa but Tana as a starting point. In conclusion, most of his account of the disease are not true. However, we can not say that he did not intentionally lie, and we may draw a conclusion that his explanation was made under scientific limits and religious prejudice or intolerance of the medieval Christian world.

Beyond the List: Bioagent-Agnostic Signatures Could Enable a More Flexible and Resilient Biodefense Posture Than an Approach Based on Priority Agent Lists Alone

As of 2021, the biothreat policy and research communities organize their efforts around lists of priority agents, which elides consideration of novel pathogens and biotoxins. For example, the Select Agents and Toxins list is composed of agents that historic biological warfare programs had weaponized or that have previously caused great harm during natural outbreaks. Similarly, lists of priority agents promulgated by the World Health Organization and the National Institute of Allergy and Infectious Diseases are composed of previously known pathogens and biotoxins. To fill this gap, we argue that the research/scientific and biodefense/biosecurity communities should categorize agents based on how they impact their hosts to augment current list-based paradigms. Specifically, we propose integrating the results of multi-omics studies to identify bioagent-agnostic signatures (BASs) of disease—namely, patterns of biomarkers that accurately and reproducibly predict the impacts of infection or intoxication without prior knowledge of the causative agent. Here, we highlight three pathways that investigators might exploit as sources of signals to construct BASs and their applicability to this framework. The research community will need to forge robust interdisciplinary teams to surmount substantial experimental, technical, and data analytic challenges that stand in the way of our long-term vision. However, if successful, our functionality-based BAS model could present a means to more effectively surveil for and treat known and novel agents alike.

The Fightback

This chapter discusses some of the barriers viruses must overcome in order to complete their life cycle. To survive, viruses must penetrate host cells before they can begin the process of reproducing their genetic material, and here again viruses appear remarkably resourceful. By carrying a molecular key on their surface, they can disguise themselves as normal body constituents, and latch on to and enter any cell which bears the complementary lock. As such, viruses infect only those cells which display the particular molecular lock that their key fits into, and this restriction dictates the type of cell a virus infects and therefore the symptoms it will cause. Since there are several hundred molecules to choose from, viruses cause a great variety of diseases. However, viruses are not fighting a one-sided battle. Even the simplest organisms have ways of dealing with viruses, but the sophistication and subtlety of the human immune system is unrivalled. The chapter then considers the vital role B and T cells play in the body’s defences. It also traces how viruses and their hosts have co-evolved. Finally, the chapter outlines the threats viruses may pose, including viral mutation and the use of viruses in biological warfare.

Protective Multifunctional Fibrous Systems Based on Natural Fibers and Metal Oxide Nanoparticles

In recent years, an unprecedented increase in the development of products and technologies to protect the human being has been observed. Now, more than ever, the world population is exposed to several threats, harmful to their well-being and health. Chemical and biological hazardous agents stand out as one of the biggest threats, not only for the military forces, but also for the civilians. Consequently, it’s essential to develop personal protective systems that are able to protect their user, not only passively, but actively, being able to detect, adsorb, degrade and decontaminate pesticides, pollutants, microorganisms and most importantly: chemical/biological warfare agents. One recent strategy for the development of active fibrous structures with improved functions and new properties is their functionalization with nanoparticles (NPs), especially metal oxides. Although their known effectiveness in the decomposition of harmful agents, the NPs could also include other functionalities in the same structure using low quantities of material, without adding extra weight, which is of huge importance for a soldier in the battlefield. The use of natural fibers as the substrate is also very interesting, since this material is a much sustainable alternative when compared to synthetic ones, also providing excellent properties.

What’s new and notable in bacterial spore killing!

Spores of many species of the orders Bacillales and Clostridiales can be vectors for food spoilage, human diseases and intoxications, and biological warfare. Many agents are used for spore killing, including moist heat in an autoclave, dry heat at elevated temperatures, UV radiation at 254 and more recently 222 and 400 nm, ionizing radiation of various types, high hydrostatic pressures and a host of chemical decontaminants. An alternative strategy is to trigger spore germination, as germinated spores are much easier to kill than the highly resistant dormant spores—the so called “germinate to eradicate” strategy. Factors important to consider in choosing methods for spore killing include the: (1) cost; (2) killing efficacy and kinetics; (3) ability to decontaminate large areas in buildings or outside; and (4) compatibility of killing regimens with the: (i) presence of people; (ii) food quality; (iii) presence of significant amounts of organic matter; and (iv) minimal damage to equipment in the decontamination zone. This review will summarize research on spore killing and point out some common flaws which can make results from spore killing research questionable.

Synthetic Biology – Friend or Foe? What Kind of Threats Should We Expect?

Synthetic biology is a newly emerging branch of dual-use technology. It is a combination of biology and different branches of engineering. The aim of this article is to show the main technological methods of synthetic biology and to give specific examples of its use to create new types of biological agents and methods of biological warfare, previously unthinkable and presented only in science fiction. Basic tools and techniques of synthetic biology are: DNA synthesis and DNA sequencing; «chassis», i.e. host system harboring the genetic toolbox for expression of the desired genes, delivered by suitable vectors, of the engineered biological pathway; engineering of transcription systems that do not deplete the resources of the cell (synthetic promotors and transcription factors); genome modification tools (CRISPR/Cas9 nuclease, zinc finger nucleases, TALE nucleases, meganucleases); computer-aided tools (involved in basic structural design and synthesis; in network design; in prediction of behavior/function/response). Synthetic biology has already demonstrared its capabilities in re-creating known pathogenic viruses and pathogenic bacteria; in making existing pathogenic bacteria and viruses more dangerous for humans; in creating new pathogens; in manufacturing toxic chemicals or biochemicals by exploiting natural and artificial metabolic pathways; in making toxic chemicals and biochemicals via in situ synthesis; in modifying the human microbiome; in modifying the human immune system; in modifying the human genome (through addition, deletion, or modification of genes or through epigenetic changes that modify gene expression and can pass from parent to child during reproduction and thus spread a genetic change through the population over time). The article discusses in detail the possibilities of synthetic biology for the development of new means of biological warfare. The author believes that it is necessary not only to constantly monitor these new dual-use biotechnologies, but also to improve traditional and scientific methods of their monitoring.