Livestock played a role in prehistoric plague infections, genomic study finds
Around 5,000 years ago, a mysterious form of plague spread throughout Eurasia, only to disappear 2,000 years later. Known only from ancient DNA, this enigmatic “LNBA plague” lineage has left scientists puzzled about its likely zoonotic origin and transmission. In a study published in Cell, this ancient plague is identified in an animal for the first time—a 4,000-year-old domesticated sheep excavated at the pastoralist site Arkaim in the Western Eurasian Steppe. Different lines of evidence suggest that plague infections in both human and sheep stem from spillover of a still unknown wild reservoir, and that widespread sheep herding during the Bronze Age brought steppe pastoralist communities into closer contact with this reservoir. This study reveals the connections between domesticated animals and the spread of one of the world’s most infamous bacteria, providing insight into how the pathogen was so successful in infecting people across thousands of kilometers over thousands of years. Zoonotic origins of prehistoric plague infections The majority of human pathogens known today have a zoonotic origin, meaning they jumped from animals into humans—a process known as spillover. A growing body of evidence suggests that many of the infectious diseases they cause emerged within the last 10,000 years—overlapping with the domestication of livestock and pets and pointing to our increasingly close relationships with these animals as the source of these diseases in humans.
Molecule can disarm pathogenic bacteria without harming beneficial microbes
A consortium of researchers with multidisciplinary skills, coordinated by INRAE and including the CNRS, the UniversitĂ© Paris-Saclay and Inserm, has identified a molecule capable of “disarming” pathogenic bacteria in the face of the immune system, without any negative effects on the host microbiota, promising a new strategy to combat antibiotic resistance. WHO, 5 million people die every year worldwide as a result of antibiotic resistance. This could become the leading cause of death by 2050. Although antibiotics have considerably reduced the mortality associated with infectious diseases, their sometimes excessive and abusive use has led to the development of bacterial resistance. Furthermore, as antibiotics generally target pathways essential for bacterial survival, they have a broad spectrum of action but lack specificity, with repercussions on all the bacteria of the host microbiota. The identification and characterization of new bacterial drug targets and the design of innovative anti-infectives is therefore a scientific and medical priority. An INRAE research team has identified the mutation frequency decline (Mfd) protein, a virulence factor produced by all bacteria and essential for them to resist the host immune system. This protein has the additional function of promoting spontaneous and random mutations, which increase the capacity of bacteria to develop resistance. Disarming the invading bacteria and protecting the microbiota Following this discovery, a consortium of researchers with multidisciplinary skills, coordinated by INRAE and including the CNRS, the UniversitĂ© Paris-Saclay and Inserm, came together to identify and develop a compound capable of blocking this protein and thus “disarming” the pathogenic bacteria. From a library of 5 million molecules, the scientists identified a promising molecule, named NM102, capable of binding to the Mfd protein and preventing its activation. They carried out a series of tests, in vitro and then in vivo in insect and mouse models, which revealed three major effects of this molecule: The molecule is thus capable of “disarming” pathogenic bacteria while protecting the bacteria in the microbiota. Most promisingly, this molecule is also effective against bacterial strains that are resistant to current treatments and originate from hospital patients.
Transparent hydrogen boride nanosheets show antimicrobial properties against multiple pathogens
The global fight against infectious diseases faces two major challenges: the threat of new pandemic outbreaks and the alarming rise of antimicrobial resistance driven by the excessive use of antibiotics. As pathogens continue to evolve and spread, researchers are urgently seeking innovative technologies that can effectively combat viruses, bacteria, and fungi conveniently in everyday settings. represent an exciting new frontier. Initially explored for potential applications in electronics, energy storage, and catalysis, the interactions between HB nanosheets and biomolecules have remained largely unexplored—until now. In a recent study, a research team involving Professor Masahiro Miyauchi and Associate Professor Akira Yamaguchi from the Department of Materials Science and Engineering at Institute of Science Tokyo, Japan, together with graduate student Andi Mauliana, Professor Takahiro Kondo from the Institute of Pure and Applied Sciences at the University of Tsukuba, Professor Takeshi Fujita from the School of Engineering at the Kochi University of Technology, researchers Dr. Kayano Sunada, Dr. Keiichi Kobayashi, Dr. Takeshi Nagai, and Dr. Hitoshi Ishiguro from Kanagawa Institute of Industrial Science and Technology, has discovered that HB nanosheets exhibit excellent antibacterial, antiviral, and antifungal properties. The researchers first fabricated transparent films by coating glass substrates with a dispersed solution of HB nanosheets. They then tested these films against a wide variety of microorganisms. The coated surfaces exhibited exceptional antimicrobial performance, inactivating the SARS-CoV-2, influenza, and feline caliciviruses down to detection limits within just 10 minutes at room temperature—without the need for light activation. Similar effects were observed against various bacteriophages, and multiple types of bacteria, such as Escherichia coli and Staphylococcus aureus, and fungi, such as Aspergillus niger and Penicillium pinophilum. The ability of HB nanosheets to inactivate these bacteria and fungi to the detection limit confirms the effectiveness of this material in combating a variety of microbial agents. The team then investigated the underlying mechanisms behind this broad-spectrum antimicrobial activity, revealing that it originates from the nanosheets’ ability to denature microbial proteins through strong physicochemical interactions. What makes these findings particularly exciting is the versatility of HB nanosheets as transparent coating materials. Unlike metal-based antimicrobials, which may leach or lack transparency, and photocatalyst-based coatings that require ultraviolet light activation, HB nanosheets function effectively in darkness and maintain optical clarity. Laboratory tests further demonstrated their effectiveness under dry conditions, mimicking real-world scenarios where pathogens might be transferred by coughing or sneezing onto everyday surfaces. Amid concerns of another pandemic like the COVID-19 outbreak, HB nanosheets can be applied as transparent coatings for items and textiles to reduce infection risks. Additionally, due to their antifungal properties, they could also be used on various materials to help maintain cleanliness in everyday surroundings.
Therapeutic vaccination against HPV-related tumors: Study shows nanoparticles make difference
Researchers from the German Cancer Research Center (DKFZ) have collaborated with the SILVACX project group at Heidelberg University to develop a therapeutic vaccination concept that can mobilize the immune system to target cancer cells. The team showed that virus peptides coupled to silica nanoparticles can elicit effective T-cell responses against HPV-related tumors. In a mouse model, the nanoparticle-based vaccine was able to partially or completely suppress HPV-related tumors. of cancer. Preventive HPV vaccinations ward off infection with the pathogens and can thus prevent the development of cancer. However, there are currently no therapeutic vaccines that combat existing precancerous lesions or tumors. A new vaccination method developed by a research team led by Angelika Riemer from the DKFZ and the SILVACX project group based at Heidelberg University relies on silica nanoparticles. This stable material, also known as silicon dioxide or silicic acid, has already proven itself in various medical applications. The silica particles are first coated to make them biocompatible. They are then loaded with short fragments of the viral proteins present in the cancer cells. To this end, the researchers select protein segments that are known to activate the human immune system. After injection, specialized immune cells—known as antigen-presenting cells—take up the particles and present the viral epitopes on their surface. This activates cytotoxic T cells, which specifically recognize and destroy cancer cells. The combination with an additional adjuvant was particularly effective. The researchers used mice whose immune systems had been “humanized,” meaning they can present the same epitopes as humans. In these animals, the vaccination led to a significant activation of cytotoxic T cells. In some of the mice, existing HPV-positive tumors were completely suppressed, and these mice survived longer. “These are encouraging results that confirm our decision to continue developing the nanoparticle vaccine system. It is versatile and could be used in the future not only against HPV-associated cancers, but also against other tumors or infectious diseases,” explains study leader Riemer. Silica nanoparticles are the core element of the therapeutic vaccination process. They protect the vaccine epitopes in the body from rapid degradation, thus ensuring their bioavailability and uptake and presentation by immune cells. They are also characterized by their stability and ease of manufacture. Vaccines based on silica nanoparticles could therefore also be used in regions where it is difficult to maintain the refrigeration chain required for most vaccines—an important advantage for global application.
Beyond health: The political effects of infectious disease outbreaks
The COVID-19 pandemic has drawn attention to the far-reaching social implications of emerging infectious diseases, bringing to mind similarly impactful events like the Black Plague in early modern Europe or the Spanish Flu after World War I. However, how emerging epidemics shape the development of political mistrust and instability has been underexplored so far. Konstanz) give empirical evidence that individuals who have experienced an infectious disease outbreak show significantly less trust in the political establishment. This is especially true of their confidence in the president, parliament and ruling party of the country they live in. “Our findings provide robust empirical evidence that deadly infectious disease outbreaks can exacerbate political polarization and undermine political stability,” the study concludes. Declining trust in political institutions The scientists focused on zoonotic disease outbreaks, i.e. diseases that originate in animal hosts and spread to humans, ranging from Ebola to H1N1 and Lassa, in several African countries. To evaluate the political impact of these outbreaks, the team combined outbreak data from the Geolocated Zoonotic Disease Outbreak Dataset (GZOD) with geolocated information from the Afrobarometer surveys. The latter database records the political and social attitudes of citizens in several African states through regular surveys, and also includes information about respondents’ trust in various political actors. To ensure that the results capture only the impact of an outbreak, the researchers “matched” individuals affected by disease outbreaks in their proximity with similar individuals from the same country who were unaffected. This approach reveals that residents that have experienced an outbreak have significantly lower levels of trust in their country’s president, parliament, ruling party, electoral commission and police force. An additional test of what happens when there are outbreaks in neighboring countries—but not in one’s home country—shows that these outbreaks abroad have no effect on political trust in the home country. “Thus, the effect does not travel across borders,” Weidmann points out.
The disease-fighting promise of mRNA
In recent years, mRNA technology enabled the rapid development of vaccines to fight COVID-19, saving millions of lives. That same mRNA-powered approach to medicine—in which synthetic mRNA is introduced into our cells and triggers an immune response—has enormous potential to produce treatments for a wide range of human illnesses and ailments, including cancer. Most recently, mRNA—short for messenger RNA—has shown tremendous promise in the treatment of pancreatic cancer in a phase 1 clinical trial. “We’re in a technological revolution in cancer research,” says Elizabeth Jaffee, deputy director of the Sidney Kimmel Comprehensive Cancer Center. “…If we can push this vaccine method forward, we will definitely have an impact on cancer that’s going to be unexpected but almost miraculous over the next five to 10 years. But potential cuts to federal funding for mRNA research and clinical trials threaten that progress. Last week, three Johns Hopkins experts—Jaffee, Jeff Coller, Bloomberg Distinguished Professor of RNA Biology and Therapeutics, and Jordan Green, professor of biomedical engineering—participated in a virtual briefing to discuss the science behind mRNA, its wide-ranging applications, and how cuts to federal funding imperil U.S. scientific leadership on mRNA technologies. How do mRNA medicines work? Coller: An mRNA medicine is a synthetic mRNA, a piece of genetic information, that we introduce into the cell in combination with a lipid nanoparticle that goes into the cytoplasm and then makes a protein of our design. Green: [mRNA medicine] enables genetic surgery: Being able to precisely heal the body at the molecular, genetic source of the disease, rather than the conventional approach of just treating the symptoms, which is how many medicines right now work. … In many ways, it’s like designing a rocket ship to Mars, … but instead of going out to outer space, it’s going to inner space—his fantastic voyage through our bodies to go to the right cells, to deliver the right instructions, to then create a whole paradigm of healing in the body.