Bacterial pathogens such as Salmonella enterica serovar Typhimurium can resist phagocytosis by macrophages. Here we explored the role of bacterial haem biosynthesis in phagocytosis resistance. Using transposon sequencing (Tn-seq) during Salmonella infection of macrophages, we identify a methyltransferase, SirM, that indirectly inhibits phagocytosis of bacteria. Mechanistically, sirM is activated upon interaction with macrophages and methylates HemL, a key enzyme in haem biosynthesis, resulting in upregulation of haem synthesis by Salmonella. Salmonella-derived haem inhibits Cdc42 activation in a Toll-like receptor 4 (TLR4)-dependent manner to inhibit phagocytosis. Moreover, sirM promotes macrophage death by increasing haem synthesis. Experiments in mouse models show that sirM is required for virulence and confers a competitive advantage over intestinal commensal bacteria during infection. We also found that sirM is distributed among enteric pathogens. Collectively, our findings show that bacterial haem promotes evasion of phagocyte responses and pathogenesis to confer an advantage in the host.

Current adaptively secure identity-based encryption (IBE) constructions from lattices are unable to achieve a good balance among the master public key size, secret key size, modulus and reduction loss. All existing lattice-based IBE schemes share a common restriction: the modulus is quadratic in the trapdoor norm. In this work, we remove this restriction and present a new adaptively secure IBE scheme from lattices in the standard model, which improves the state-of-the-art construction proposed by Abla et al. (TCC 2021) and achieves asymptotically better efficiency. More precisely, we achieve the asymptotically minimal number of public vectors among all the existing schemes, along with a significantly smaller modulus compared to the scheme by Abla et al. (TCC 2021). Furthermore, our scheme enjoys the smallest Gaussian width of the secret key among all existing schemes and has the same tightness as Abla et al.’s scheme. We propose a novel cross-multiplication design for our IBE scheme, along with several novel tools and techniques, including: (a) a homomorphic computation algorithm that outputs BGG+-style encoding with two distinct-norm trapdoors; (b) a sampling algorithm with hybrid Gaussian outputs; and (c) a partial rerandomization algorithm. These new tools and techniques are general and could find rich applications in lattice-based cryptography.

Most adaptively secure identity-based encryption (IBE) constructions from lattices in the standard model follow the framework proposed by Agrawal et al. (EUROCRYPT 2010). However, this framework has an inherent restriction: the modulus is quadratic in the trapdoor norm. This leads to an unnecessarily large modulus, reducing the efficiency of the IBE scheme. In this paper, we propose a novel framework for adaptively secure lattice-based IBE in the standard model, that removes this quadratic restriction of modulus while keeping the dimensions of the master public key, secret keys, and ciphertexts unchanged. More specifically, our key observation is that the original framework has a natural cross-multiplication structure of trapdoor. Building on this observation, we design two novel algorithms with non-spherical Gaussian outputs that fully utilize this structure and thus remove the restriction. Furthermore, we apply our framework to various IBE schemes with different partitioning functions in both integer and ring settings, demonstrating its significant improvements and broad applicability. Besides, compared to a concurrent and independent work by Ji et al. (PKC 2025), our framework is significantly simpler in design, and enjoys a smaller modulus, a more compact master public key and shorter ciphertexts.

To understand the dynamic interplay between the human microbiome and host during health and disease, we analyzed the microbial composition, temporal dynamics, and associations with host multi-omics, immune, and clinical markers of microbiomes from four body sites in 86 participants over 6 years. We found that microbiome stability and individuality are body-site specific and heavily influenced by the host. The stool and oral microbiome are more stable than the skin and nasal microbiomes, possibly due to their interaction with the host and environment. We identify individual-specific and commonly shared bacterial taxa, with individualized taxa showing greater stability. Interestingly, microbiome dynamics correlate across body sites, suggesting systemic dynamics influenced by host-microbial-environment interactions. Notably, insulin-resistant individuals show altered microbial stability and associations among microbiome, molecular markers, and clinical features, suggesting their disrupted interaction in metabolic disease. Our study offers comprehensive views of multi-site microbial dynamics and their relationship with host health and disease.

We developed an analysis pipeline that can extract microbial sequences from spatial transcriptomic (ST) data and assign taxonomic labels, generating a spatial microbial abundance matrix in addition to the default host expression matrix, enabling simultaneous analysis of host expression and microbial distribution. We called the pipeline spatial metatranscriptome (SMT) and applied it on both human and murine intestinal sections and validated the spatial microbial abundance information with alternative assays. Biological insights were gained from these novel data that showed host-microbe interaction at various spatial scales. Finally, we tested experimental modification that can increase microbial capture while preserving host spatial expression quality and, by use of positive controls, quantitatively showed the capture efficiency and recall of our methods. This proof-of-concept work shows the feasibility of SMT analysis and paves the way for further experimental optimization and application.

ABSTRACT Salmonella could survive and replicate in macrophages, where it encounters multiple stresses. Deficiency of a DNA adenine methyltransferase impairs the survival of Salmonella enterica serovar Typhimurium (S. Typhimurium) in hydrogen peroxide. To investigate whether DNA methylation is involved in the expression of oxidative stress-responsive genes, we combined RNA-seq and single-molecule real-time sequencing to integrate transcriptome and methylome analysis. Here, we show that (i) the entire amount of m6A GATC remains stable during oxidative stress; (ii) no significant association is observed between DNA methylation and transcription level in most genes; (iii) coincidence of level change between transcription and m6A GATC in the regulatory regions is identified in 49 genes under oxidative stress. Some of them are known to contribute to bacterial defenses against oxidative stress through reducing H2O2 levels, directing aberrant protein product degradation and inducing outer membrane protein expression. Specifically, the transcription level of ahpCF is negatively correlated to the m6A GATC level in its regulatory region. The transcription of smpB is elevated along with the decrease in m6A level at position 2,879,954 on the minus strand. In contrast, mRNA levels of STM14_2773 and ycfR are positively correlated with m6A GATC content in their regulatory regions. Highly stable DNA methylome and coupled change of m6A GATC with gene expression in specific positions suggest that DNA methylation homeostasis at genome-wide and plasticity in specific regions are crucial for bacterial response to oxidative stress. These findings provide new insights into the epigenetic regulatory mechanisms of gene expression in S. Typhimurium in the host microenvironment. IMPORTANCE The intracellular pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) comes across a wide variety of stresses from entry to dissemination, such as reactive oxygen species. To adapt itself to oxidative stress, Salmonella must adopt various and complex strategies. In this study, we revealed that DNA adenine methyltransferase was essential for S. Typhimurium to survive in hydrogen peroxide. We then screened out oxidative stress-responsive genes that were potentially regulated by DNA methylation in S. Typhimurium. Our results show that the DNA methylome is highly stable throughout the genome, and the coupled change of m6A GATC with gene expression is identified in only a few positions, which suggests the complexity of the DNA methylation and gene expression regulation networks. The results may shed light on our understanding of m6A-mediated gene expression regulation in bacteria.

Anonymity of public key encryption (PKE) requires that, in a multi-user scenario, the PKE ciphertexts do not leak information about which public keys are used to generate them. Corruptions are common threats in the multi-user scenario but anonymity of PKE under corruptions is less studied in the literature. In TCC 2020, Benhamouda et al. first provide a formal characterization for anonymity of PKE under a specific type of corruption. However, no known PKE scheme is proved to meet their characterization. To the best of our knowledge, all the PKE application scenarios which require anonymity also require confidentiality. However, in the work by Benhamouda et al., different types of corruptions for anonymity and confidentiality are considered, which can cause security pitfalls. What's worse, we are not aware of any PKE scheme which can provide both anonymity and confidentiality under the same types of corruptions. In this work, we introduce a new security notion for PKE called ANON-RSO $$_{ {k} }$$ &C security, capturing anonymity under corruptions. We also introduce SIM-RSO $$_{ {k} }$$ &C security which captures confidentiality under the same types of corruptions. We provide a generic framework of constructing PKE scheme which can achieve the above two security goals simultaneously based on a new primitive called key and message non-committing encryption (KM-NCE). Then we give a general construction of KM-NCE utilizing a variant of hash proof system (HPS) called Key-Openable HPS. We also provide Key-Openable HPS instantiations based on the matrix decisional Diffie-Hellman assumption. Therefore, we can obtain various concrete PKE instantiations achieving the two security goals in the standard model with compact ciphertexts. Furthermore, for some PKE instantiation, its security reduction is tight.

OBJECTIVE:The aims of this study were to evaluate the safety and probiotic characteristics of the newly isolated Enterococcus lactis strain JDM1.METHODS:Safety assessment of E. lactis JDM1 was accomplished by the combination of whole genome sequence information analysis and phenotypic assays, including antimicrobial susceptibility test, haemolysis assay, biogenic amine production assay, cytotoxicity assay. The bacteriostatic experiment and gastrointestinal tolerance experiment were also conducted to evaluate its applicability.RESULTS:E. lactis JDM1 possesses good gastrointestinal tolerance and can inhibit the growth of the pathogenic bacteria Clostridioides difficile and Listeria monocytogenes. The chromosome size of JDM1 was 2,570,998 bp with a GC content of 38.46%, which contained a plasmid. One intact prophage, 13 genomic islands and 19 IS elements were predicted in the JDM1 chromosome. Five resistance-related genes and seven virulence-related genes were predicted in the genome. Most resistance genes were conserved, and virulence factors were not related to functional pathogenicity. Antimicrobial susceptibility tests showed that JDM1 was sensitive to tedizolid, ciprofloxacin, levofloxacin, penicillin, ampicillin, vancomycin, linezolid, tetracycline, high-level gentamicin and high-level streptomycin. Genes encoding putative enzymes responsible for adverse metabolites were not found and JDM1 was unable to produce the six main biogenic amines. Cytotoxicity test showed that the JDM1 supernatant had no toxic effect.CONCLUSION:E. lactis JDM1 is expected to be developed as a probiotic, and its probiotic properties are worthy of further exploration.

Adaptation to various stresses during infection is important for Salmonella Typhimurium virulence, while the fitness determinants under infection-relevant stress conditions remain unknown. Here, we simulated conditions Salmonella encountered within the host or in the environment by 15 individual stresses as well as two model cell lines (epithelium and macrophage) to decipher the genes and pathways required for fitness. By high-resolution Tn-seq analysis, a total of 1242 genes were identified as essential for fitness under at least one stress condition. The comparative analysis of fitness determinants in 17 stress conditions indicated the essentiality of genes varied in different mimicking host niches. A total of 12 genes were identified as fitness determinants in all stress conditions, including recB, recC, and xseA (encode three exonuclease subunits necessary for DNA recombination repair) and a novel essential fitness gene yheM. YheM is a putative sulfurtransferase subunit that is responsible for tRNA modification, and our results showed that Salmonella lacking yheM accumulated more aggregates of endogenous protein than wild-type. Moreover, we established a scoring scheme for sRNA essentiality analysis and found STnc2080 of unknown function was essential for resistance to LL-37. In summary, we systematically dissected Salmonella gene essentiality profiling and demonstrated the general and specific adaptive requirements in infection-relevant niches. Our data not only provide valuable insights on how Salmonella responds to environmental stresses during infections but also highlight the potential clinical application of fitness determinants in vaccine development.

Fundamental to viral biology is identification and annotation of viral genes and their function. Determining the level of coronavirus gene expression is inherently difficult due to the positive stranded RNA genome and the identification of subgenomic RNAs (sgRNAs) that are required for expression of most viral genes. We developed a bioinformatic pipeline to analyze metatranscriptomic data from 20 independent studies encompassing 588 individual samples and 10 coronavirus species. This comparative analysis defined a core sgRNA repertoire for SARS-CoV-2 and found novel sgRNAs that could encode functional short peptides. Relevant to coronavirus infectivity and transmission, we also observed that the ratio of Spike sgRNA to Nucleocapsid one is highest in SARS-CoV-2, among the β-coronaviruses examined. Furthermore, the adjustment of this ratio can be made by modifications to the viral RNA replication machinery, representing a form of viral gene regulation that may be involved in host adaption.

It is well known that already the length of encrypted messages may reveal sensitive information about encrypted data. Fingerprinting attacks enable an adversary to determine web pages visited by a user and even the language and phrases spoken in voice-over-IP conversations. Prior research has established the general perspective that a length-hiding padding which is long enough to improve security significantly incurs an unfeasibly large bandwidth overhead. We argue that this perspective is a consequence of the choice of the security models considered in prior works, which are based on classical indistinguishability of two messages, and that this does not reflect the attacker model of typical fingerprinting attacks well. Therefore we propose a new perspective on length-hiding encryption, which aims to capture security against fingerprinting attacks more accurately. This makes it possible to concretely quantify the security provided by length-hiding padding against fingerprinting attacks, depending on the real message distribution of an application. We find that for many real-world applications (such as webservers with static content, DNS requests, Google search terms, or Wikipedia page visits) and their specific message distributions, even length-hiding padding with relatively small bandwidth overhead of only 2–5% can already significantly improve security against fingerprinting attacks. This gives rise to a new perspective on length-hiding encryption, which helps understanding how and under what conditions length-hiding encryption can be used to improve security.

We construct the currently most efficient signature schemes with tight multi-user security against adaptive corruptions. It is the first generic construction of such schemes, based on lossy identification schemes (Abdalla et al.; JoC 2016), and the first to achieve strong existential unforgeability. It also has significantly more compact signatures than the previously most efficient construction by Gjøsteen and Jager (CRYPTO 2018). When instantiated based on the decisional Diffie– Hellman assumption, a signature consists of only three exponents. We propose a new variant of the generic construction of signatures from sequential OR-proofs by Abe, Ohkubo, and Suzuki (ASIACRYPT 2002) and Fischlin, Harasser, and Janson (EUROCRYPT 2020). In comparison to Fischlin et al., who focus on constructing signatures in the nonprogrammable random oracle model (NPROM), we aim to achieve tight security against adaptive corruptions, maximize efficiency, and to directly achieve strong existential unforgeability (also in the NPROM). This yields a slightly different construction and we use slightly different and additional properties of the lossy identification scheme. Signatures with tight multi-user security against adaptive corruptions are a commonly-used standard building block for tightly-secure authenticated key exchange protocols. We also show how our construction improves the efficiency of all existing tightly-secure AKE protocols.

The standard security notion for digital signatures is “single-challenge” (SC) EUF-CMA security, where the adversary outputs a single message-signature pair and “wins” if it is a forgery. Auerbach et al. (CRYPTO 2017) introduced memory-tightness of reductions and argued that the right security goal in this setting is actually a stronger “multi-challenge” (MC) definition, where an adversary may output many message-signature pairs and “wins” if at least one is a forgery. Currently, no construction from simple standard assumptions is known to achieve full tightness with respect to time, success probability, and memory simultaneously. Previous works showed that memory-tight signatures cannot be achieved via certain natural classes of reductions (Auerbach et al., CRYPTO 2017; Wang et al., EUROCRYPT 2018). These impossibility results may give the impression that the construction of memory-tight signatures is difficult or even impossible.We show that this impression is false, by giving the first constructions of signature schemes with full tightness in all dimensions in the MC setting. To circumvent the known impossibility results, we first introduce the notion of canonical reductions in the SC setting. We prove a general theorem establishing that every signature scheme with a canonical reduction is already memory-tightly secure in the MC setting, provided that it is strongly unforgeable, the adversary receives only one signature per message, and assuming the existence of a tightly-secure pseudorandom function. We then achieve memory-tight many-signatures-per-message security in the MC setting by a simple additional generic transformation. This yields the first memory-tightly, strongly EUF-CMA-secure signature schemes in the MC setting. Finally, we show that standard security proofs often already can be viewed as canonical reductions. Concretely, we show this for signatures from lossy identification schemes (Abdalla et al., EUROCRYPT 2012), two variants of RSA Full-Domain Hash (Bellare and Rogaway, EUROCRYPT 1996), and two variants of BLS signatures (Boneh et al., ASIACRYPT 2001).

Colitis induced by C. difficile is one of the most common and costly healthcare-related infections for humans. Probiotics are one of the most promising approaches for controlling CDI. Here, we presented the isolation, safety, and probiotic property evaluation of a novel E. thailandicus strain, d5B, with effective antimicrobial activity against C. difficile. Strain d5B showed strong bactericidal effects on at least 54C. difficile strains. Safety tests showed that strain d5B was sensitive to clinically important antibiotics, and had no haemolytic and cytotoxic activities. Whole genomic analysis showed strain d5B only contained one aminoglycoside resistance gene located in the chromosome. Moreover, d5B was devoid of functional virulence genes. Finally, strain d5B exhibited probiotic properties, such as tolerance to the gastrointestinal tract, and adhered well to HT-29 cells. In conclusion, the E. thailandicus strain d5B should be investigated further for useful properties as a novel candidate probiotic for controlling CDI.

ABSTRACTBackgroundFundamental to viral biology is identification and annotation of viral genes and their function. Determining the level of coronavirus gene expression is inherently difficult due to the positive stranded RNA genome and the identification of sub-genomic RNAs (sgRNAs) that are required for expression of most viral genes. In the COVID-19 epidemic so far, few genomic studies have looked at viral sgRNAs and none have systematically examined the sgRNA profiles of large numbers of SARS-CoV2 datasets in conjuction with data for other coronaviruses.ResultsWe developed a bioinformatic pipeline to analyze the sgRNA profiles of coronaviruses and applied it to 588 individual samples from 20 independent studies, covering more than 10 coronavirus species. Our result showed that SARS-CoV, SARS-CoV-2 and MERS-CoV each had a core sgRNA repertoire generated via a canonical mechanism. Novel sgRNAs that encode peptides with evolutionarily conserved structures were identified in several coronaviruses and were expressed in vitro and in vivo. Two novel peptides may have direct functional relevance to disease, by alluding interferon responses and disrupting IL17E (IL25) signaling. Relevant to coronavirus infectivity and transmission, we also observed that the level of Spike sgRNAs were significantly higher in-vivo than in-vitro, while the opposite held true for the Nucleocapside protein.ConclusionsOur results greatly expanded the predicted number of coronaviruses proteins and identified potential viral peptide suggested to be involved in viral virulence. These methods and findings shed new light on coronavirus biology and provides a valuable resource for future genomic studies of coronaviruses.

We propose the concept of quasi-adaptive hash proof system (QAHPS), where the projection key is allowed to depend on the specific language for which hash values are computed. We formalize leakage-resilient(LR)-ardency for QAHPS by defining two statistical properties, including LR-< L-0, L-1 >-universal and LR-< L-0, L-1 >-key-switching. We provide a generic approach to tightly leakage-resilient CCA (LR-CCA) secure public-key encryption (PKE) from LR-ardent QAHPS. Our approach is reminiscent of the seminal work of Cramer and Shoup (Eurocrypt'02), and employ three QAHPS schemes, one for generating a uniform string to hide the plaintext, and the other two for proving the well-formedness of the ciphertext. The LR-ardency of QAHPS makes possible the tight LR-CCA security. We give instantiations based on the standard k-Linear (k-LIN) assumptions over asymmetric and symmetric pairing groups, respectively, and obtain fully compact PKE with tight LR-CCA security. The security loss is O(log Q(e)) where Q(e) denotes the number of encryption queries. Specifically, our tightly LR-CCA secure PKE instantiation from SXDH has only 4 group elements in the public key and 7 group elements in the ciphertext, thus is the most efficient one.

Structure-preserving primitives are important building blocks in cryptographic protocols. Up to now, the only structure-preserving public-key encryption (SP-PKE) with CCA security over asymmetric pairing groups is based on the SXDH assumption, due to Libert et al. [18]. In this work, we propose a general framework of constructing SP-PKE with leakage-resilient CCA security (which implies the IND-CCA2 security). The corresponding instantiations result in the first leakage-resilient CCA secure SP-PKE from the Matrix Decision Diffie-Hellman (MDDH) assumption (including the SXDH and k-Linear assumptions) over asymmetric pairing groups. The ciphertext of our SP-PKE also enjoys the publicly verifiable property.

Quasi-Adaptive Non-Interactive Zero-Knowledge (QANIZK) proofs make possible efficient NIZK with short proofs by allowing the common reference string to depend on the language. The strongest notion of (computational) soundness for QANIZK is Unbounded Simulation-Soundness (USS). For USS, however, the language is completely beyond the adversary's control. In this paper, we introduce a stronger notion of USS for QANIZK, called USS for Adversary-Dependent Languages (USS-ADL), by allowing the adversary to adaptively develop the language. We present a generic construction of efficient USS-ADL-QANIZK for diverse vector spaces (DVS) over graded rings , of which linear subspaces over bilinear groups are specific instantiations. – Our generic construction provides the first USS-QANIZK for DVS over graded rings . This complements Abdalla et al.'s work (Eurocrypt'15) of QANIZK with one-time simulation-soundness. – As for applications, USS-ADL-QANIZK leads to modular constructions of digital signature and linearly homomorphic (structure-preserving) signature schemes with black-box security reductions . The instantiations cover the efficient USS-QANIZK for linear subspaces over bilinear groups proposed by Kiltz and Wee (Eurocrypt'15), a variant of the efficient structure-preserving signature proposed by Kiltz et al. (Crypto'15) and the efficient linearly homomorphic structure-preserving signature proposed by Kiltz and Wee (Eurocrypt'15). Our USS-ADL-QANIZK provides a new perspective on their constructions and security proofs in a unified way.

Selective opening security (SO security) is desirable for public key encryption (PKE) in a multi-user setting. In a selective opening attack, an adversary receives a number of ciphertexts for possibly correlated messages, then it opens a subset of them and gets the corresponding messages together with the randomnesses used in the encryptions. SO security aims at providing security for the unopened ciphertexts. Among the existing simulation-based, selective opening, chosen ciphertext secure (SIM-SO-CCA secure) PKEs, only one (Libert et al. Crypto'17) enjoys tight security, which is reduced to the Non-Uniform LWE assumption. However, their public key and ciphertext are not compact. In this work, we focus on constructing PKE with tight SIM-SO-CCA security based on standard assumptions. We formalize security notions needed for key encapsulation mechanism (KEM) and show how to transform these securities into SIM-SO-CCA security of PKE through a tight security reduction, while the construction of PKE from KEM follows the general framework proposed by Liu and Paterson (PKC'15). We present two KEM constructions with tight securities based on the Matrix Decision Diffie-Hellman assumption. These KEMs in turn lead to two tightly SIM-SO-CCA secure PKE schemes. One of them enjoys not only tight security but also compact public key.

In a selective-opening, chosen-ciphertext attack (SO-CCA) against a public key encryption scheme (PKE scheme), a probabilistic polynomial time (PPT) adversary obtains a vector of challenge ciphertexts, has access to a decryption oracle, adaptively selects to open some of the challenge ciphertexts and sees the corresponding messages together with the random coins. The simulation-based, selective-opening security against chosen-ciphertext attacks (SIM-SO-CCA security) protects the security of the unopened messages in a semantic way, i.e. it requires that the output of the adversary can be simulated by a simulator who sees only the opened messages. In particular, all information that the adversary can get from the unopened messages can also be simulated from the opened messages alone by the simulator. All security proofs of the available PKEs achieving SIM-SO-CCA security are not tight, and the security loss depends either on the number of challenge ciphertexts or on the number of decryption queries. In this work, we present the first PKE scheme which achieves SIM-SO-CCA security with a tight reduction to standard assumptions. This partially solves the open problem proposed by Hofheinz in EuroCrypt 2012.