Quantum-resistance in blockchain networks.

The advent of quantum computing threatens blockchain protocols and networks because they utilize non-quantum resistant cryptographic algorithms. When quantum computers become robust enough to run Shor's algorithm on a large scale, the most used asymmetric algorithms, utilized for digital signatures and message encryption, such as RSA, (EC)DSA, and (EC)DH, will be no longer secure. Quantum computers will be able to break them within a short period of time. Similarly, Grover's algorithm concedes a quadratic advantage for mining blocks in certain consensus protocols such as proof of work. Today, there are hundreds of billions of dollars denominated in cryptocurrencies and other digital assets that rely on blockchain ledgers as well as thousands of blockchain-based applications storing value in blockchain networks. Cryptocurrencies and blockchain-based applications require solutions that guarantee quantum resistance in order to preserve the integrity of data and assets in these public and immutable ledgers. The quantum threat and some potential solutions are well understood and presented in the literature. However, most proposals are theoretical, require large QKD networks, or propose new quantum-resistant blockchain networks to be built from scratch. Our work, which is presented in this paper, is pioneer in proposing an end-to-end framework for post-quantum blockchain networks that can be applied to existing blockchain to achieve quantum-resistance. We have developed an open-source implementation in an Ethereum-based (i.e., EVM compatible) network that can be extended to other existing blockchains. For the implementation we have (i) used quantum entropy to generate post-quantum key pairs, (ii) established post-quantum TLS connections and X.509 certificates to secure the exchange of information between blockchain nodes over the internet without needing a large QKD network, (iii) introduced a post-quantum second signature in transactions using Falcon-512 post-quantum keys, and (iv) developed the first on-chain verification of post-quantum signatures using three different mechanisms that are compared and analyzed: Solidity smart-contracts run by the validators for each transaction, modified EVM Opcode, and precompiled smart contracts.

Granzyme B Attenuates Bacterial Virulence by Targeting Secreted Factors.

Pathogenic bacteria secrete virulence factors that interact with the human host to establish infections. The human immune system evolved multiple mechanisms to fight bacterial invaders, including immune proteases that were demonstrated to contribute crucially to antibacterial defense. Here we show that granzyme B degrades multiple secreted virulence mediators from Listeria monocytogenes, Salmonella typhimurium, and Mycobacteria tuberculosis. Pathogenic bacteria, when infected in the presence of granzyme B or granzyme-secreting killer cells, fail to grow in human macrophages and epithelial cells owing to their crippled virulence. A granzyme B-uncleavable mutant form of the major Listeria virulence factor, listeriolysin O, rescued the virulence defect in response to granzyme treatment. Hence, we link the degradation of a single factor with the observed decrease in virulent bacteria growth. Overall, we reveal here an innate immune barrier function of granzyme B by disrupting bacterial virulence to facilitate bacteria clearance by bystander immune and non-immune cells.

Killing Bacteria with Cytotoxic Effector Proteins of Human Killer Immune Cells: Granzymes, Granulysin, and Perforin.

Bacterial pathogens represent a constant threat to human health that was exacerbated in recent years by a dramatic increase of strains resistant to last resort antibiotics. The immune system of higher vertebrates generally evolved several efficient innate and adaptive mechanisms to fight ubiquitous bacterial pathogens. Among those mechanisms, immune proteases were recognized to contribute essentially to antibacterial immune defense. The effector serine proteases of the adaptive immune system, the granzymes, exert potent antimicrobial activity when they are delivered into the bacterial cytosol by prokaryotic membrane disrupting proteins, such as granulysin.In this chapter, we are detailing experimental protocols to study the synergistic cytotoxic effects of human granzymes and granulysin on extracellular as well as on intracellular bacterial pathogens in vitro. In addition, we provide a simple and fast-forward method to biochemically purify native cytotoxic effector molecules necessary to perform this kind of investigations.