Virulence最新文献

Since the outbreak of coronavirus disease 2019 (COVID-19), the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continuously mutated and evolved, causing several waves of infection. Predicting the evolutionary and epidemiological dynamics of SARS-CoV-2 remains a challenge. This study combines the epidemic data of different variants of SARS-CoV-2 in South Africa to predict their evolutionary and epidemiological dynamics. Based on the susceptible-infectious-recovered-susceptible (SIRS) transmission dynamics, we consider the transmission rate as an evolutionary trait and the disease-deduced mortality and recovery rates as trade-off functions of the trait. Using the adaptive dynamics method, combined with the epidemic data of the five most recent variants in South Africa, we find that South Africa will be continuously invaded and infected by the new mutant strain with a higher transmission rate. In addition, we find that changing the recovery rate by enhancing treatment, for example, will alter the trade-off function and thereby affect the evolutionary dynamics of SARS-CoV-2, which may evolve into a continuously stable strategy. This study is the first to use evolutionary dynamics theory to predict the future evolutionary and epidemiological dynamics of SARS-CoV-2, which is helpful for the government to predict the epidemic dynamics of COVID-19 and to take effective measures in advance, and it is proposed that advancing treatment time and improving treatment efficiency will contribute to disease control.

Duck enteritis virus (DEV) was identified as the etiological agent responsible for an outbreak of morbidity and mortality in adult ducks on a farm in Jiangsu, China. Diagnostic approaches confirmed that the outbreak was caused by the highly pathogenic DEV-JS2024 isolate. The clinical progression of the disease, characterized by lethargy, anorexia, ocular discharge, and high mortality, was accompanied by extensive hemorrhagic lesions in critical organs such as the liver, spleen, lungs, and bursa of Fabricius, consistent with known signs of DEV infection. Genomic analysis of DEV-JS2024 revealed a 45% G+C content and 76 open reading frames. BLASTn analysis revealed that the genome of DEV-JS2024 shares the highest sequence similarity with the Chinese virulent strain CV and the DEV attenuated vaccine strain C-KCE in the database. These results indicate a close genetic relationship between DEV-JS2024 and both the virulent and attenuated strains, suggesting potential similarities in their genomic architecture. Comparative genomic analysis identified 28 nucleotide mutations, including 15 non-synonymous mutations potentially related to virulence factors. The study also highlighted the first reported 528 base pairs deletion in the UL2 gene of a virulent strain, challenging its utility as a marker for distinguishing virulent from attenuated strains. Phylogenetic analysis suggested that DEV-JS2024 may result from recombination between the vaccine and virulent strains, further complicating our understanding of DEV pathogenicity. This study provides new insights into the molecular evolution of DEV and stresses the importance of continued genomic surveillance to enhance vaccine development and control measures for duck plague.

This study aimed to investigate the molecular epidemiology of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) ST23 in China. We conducted comprehensive searches across five databases (PubMed, Web of Science, MEDLINE, CNKI, and Wanfang) spanning 1980-2024, identifying 30 eligible studies through rigorous screening. Our synthesis documents 120 ST23 CR-hvKP clinical isolates, including the earliest known case from Zhejiang in 2013 which harbored bla_KPC-2 alongside hallmark virulence loci (rmpA, rmpA2, iroN, iucA, and pagO). Epidemiological analysis of 119 isolates reveals geographic disparities: Hebei (25.2%) and Jiangxi (22.7%) are hotspots, while carbapenemase distribution exhibits a north-south divide (bla_NDM predominating in northern China versus bla_KPC in the south). Phylogenetic analysis of 584 global ST23 genomes suggests independent plasmid-mediated acquisition of carbapenemase genes, with evidence of clonal transmission both among humans and between humans and environmental niches. This review highlights the urgent need for surveillance to track CR-hvKP's evolving epidemiology, alongside interventions targeting plasmid-driven resistance spread.

Staphylococcus aureus (S. aureus) infection can lead to the occurrence of hypoxia, however, the underlying mechanisms have not been fully elucidated. β-hemolysin (Hlb) induced hemolysis of red blood cells (RBCs) requires a temperature transition from "hot" to "cold," a phenomenon not observed under physiological conditions. In this study, we discovered that RBCs treated with Hlb exhibited a high level of intracellular Ca²⁺ and underwent a shape transformation from biconcave discoid to spherical, which was contingent upon the degradation of sphingomyelin of the cell membrane and led to impaired oxygen transport. The increase in intracellular Ca²⁺ levels induced by Hlb was dependent on the activation of the ion channel N-methyl-D-aspartate receptor. Furthermore, we found that Hlb-induced Ca²⁺ influx increased the cytoplasmic pH and subsequently attenuated the oxygen release from RBCs, which were also observed in both hlb transgenic mice and a murine model with S. aureus challenge. Our findings reveal a novel role for Hlb as sphingomyelinase in impairing RBC function under non-lytic conditions, shedding light on the mechanism behind hypoxia associated with S. aureus infection.

The complement system, along with its intricate network, constitutes a vital component of the innate immune response, playing a pivotal role in defending the host against invading pathogens. While it is essential for maintaining immune homeostasis, dysregulation of this system can lead to significant pathological consequences: deficiencies in complement components increase susceptibility to infections, whereas excessive activation causes inflammatory tissue damage. Through its diverse functions and regulatory mechanisms, including but not limited to cytolytic effects, opsonophagocytosis, induction of inflammatory responses, and facilitation of antigen presentation, the complement system can independently or synergistically eliminate pathogens with high specificity and efficiency. In response to this robust immune defense strategy, pathogens have evolved a range of sophisticated evasion and resistance mechanisms to counteract the lethal effects of complements. In-depth research into these complement-pathogen interactions enhances our understanding of disease pathogenesis and progression, providing vital theoretical foundations and potential targets for novel therapeutics.

The association between chronic hepatitis B virus (HBV) infection and metabolic syndrome (MetS) remains controversial. We aimed to analyze the causal effects of chronic HBV infection on MetS components and vice versa. Mendelian randomization (MR) was applied to explore the genetic association of chronic HBV infection with both metabolic risk factors and metabolic diseases using summary-level data from GWAS. Further colocalization and mediation analyses were performed for traits with significant causal relationships. The effect of HBV on lipid metabolism was validated by in vitro assays. In European populations, the MR analyses did not support causal relationships between chronic HBV infection and metabolic traits. In East Asian populations, chronic HBV infection was associated with decreased low-density lipoprotein (LDL) and reduced risk of coronary artery disease (CAD). Reversely, CAD showed negative causal effects on chronic HBV infection risk. Colocalization analysis revealed that the association between chronic HBV infection and CAD was most likely driven by distinct rather than shared causal variants. Mediation analysis identified LDL as a major mediator in the causal effect of chronic HBV infection on CAD and aspirin use as the primary mediator in the causal effect of CAD on chronic HBV infection. In vitro experiments suggested that HBV may inhibit glucose plus insulin-induced lipogenesis in hepatocytes. Our results provide genetic evidence of chronic HBV infection as a protective factor against dyslipidemia and CAD and reveal the potential causal effect of CAD on genetically proxied chronic HBV infection via aspirin treatment in East Asian populations.

Enterobactin, a high-affinity siderophore produced by Escherichia coli and other enteric pathogens, plays a critical role in bacterial iron acquisition and virulence. By sequestering iron from host environments, enterobactin enables bacterial survival and proliferation, even under iron-limited conditions typical of host tissues. This review explores the biosynthesis and regulation of enterobactin, highlighting its contribution to bacterial pathogenesis and immune evasion. We discuss the potential of targeting enterobactin for the development of live-attenuated vaccines, emphasizing the attenuation of virulence through genetic knockout of enterobactin biosynthesis genes (e.g. entB). Additionally, we examine enterobactin as a promising target for novel antimicrobial strategies, including small-molecule inhibitors and siderophore-based "Trojan horse" antibiotics. Beyond medical applications, we also explore the biotechnological and environmental potential of enterobactin, such as its use in bioremediation and drug delivery systems. Finally, we identify key gaps in current research and propose future directions for harnessing enterobactin to combat bacterial infections and address global health challenges. This review underscores the multifaceted role of enterobactin in bacterial biology and its potential as a cornerstone for innovative therapeutic and biotechnological applications.

Bovine parvovirus (BPV) is among the pathogens associated with respiratory, digestive, and reproductive disorders in cattle, contributing to significant economic losses in the global cattle industry. To investigate the prevalence and genetic variability of BPV in diarrheic cattle, 14 BPV strains were isolated from 673 bovine diarrhea samples (2017-2022, Northeast China) using BT cells. Notably, the DQ7498 strain exhibited the highest proliferation efficiency (titer reaching 10^8.12TCID₅₀/mL). Sensitive cell detection assays showed isolated strains stably serially passaged only in BT and bovine lung cells. Electron microscopy revealed that all isolates as non-enveloped icosahedrons structures (approximately 25 nm in diameter), consistent with parvovirus morphology. Complete coding sequence (CDS) and phylogenetic analysis revealed that the 14 isolates strains were closely related to BPV1 reference strains (DQ335247, NC001540), with high genetic identity (96.5%-99%). Recombination analysis identified genomic recombination events in four strains (JL108, JL60, DQ7706 and DQ7728), suggesting DQ8186 and ZD0510, or earlier unisolated strains, as potential parental strains. Amino acid sequence analysis revealed multiple coding mutations among the 14 isolates. Although antigenic epitope mutations (A362T and N399D) were identified in VP2, they did not induce significant conformational changes. Physicochemical characterization demonstrated that the virus exhibited sensitivity to chloroform and loses its infectivity after chloroform treatment, which is inconsistent with previous research reports. This study reports the first isolation of 14 BPV1 strains in Northeast China, revealing BPV1 genetic evolution, antigenic variation, and the first documented recombination events among regional strains, providing new insights into the molecular evolution of BPV1 and disease control.

Melioidosis, a fatal tropical disease, presents a wide array of clinical manifestations, including abscesses, pneumonia, septic shock, bacteraemia, osteomyelitis, septic arthritis, and skin infection. The Centers for Disease Control and Prevention (CDC) has classified Burkholderia pseudomallei (B. pseudomallei), a gram-negative bacterium found in soil, as a Tier 1 select agent. Referred to as the "great mimicker," this organism can infect several organs imitating the symptoms of different illnesses. According to worldwide data, there are around 165,000 cases and 89,000 deaths annually. Current diagnostic procedures rely primarily on culturing B. pseudomallei, are slow and have low sensitivity, resulting in delayed treatment and higher fatality rates. This review examines the substantial difficulties related to diagnosing melioidosis in response to the urgent need for precise and prompt diagnosis. We have summarized the results of diagnostic kits that are currently sold in the market and assessed the market for melioidosis diagnostic kits.

Non-Hodgkin lymphoma (NHL), a heterogeneous lymphoid malignancy, demonstrates molecular diversity linked to genetic and immune factors, with emerging roles for viral infections in pathogenesis. Yet, the blood virome's composition and dynamics in NHL remain poorly characterized. This study characterizes the blood virome in NHL subtypes using viral metagenomic sequencing of serum from 217 patients (B-cell: BCL, T-cell: TCL, NK-cell: NKCL) and 40 healthy controls. Bioinformatic analysis identified 45 viral families, revealing subtype-specific viromic signatures. BCL exhibited a dominance of Anelloviridae, which accounted for 86% of eukaryotic viruses, compared with only 3% in controls, correlating with immunosuppression. Additionally, picobirnavirus, an opportunistic pathogen particularly in hosts with compromised immune systems, also showed a significant difference compared to controls. NKCL showed Flaviviridae enrichment, accounting for 82% of eukaryotic viruses, with nearly all of them being human pegivirus-1 (HPgV-1). Compared with healthy controls, patients with NHL exhibited significantly lower blood virome α-diversity at the genus level, and T-cell lymphomas showed the lowest species-level richness (140 vs. 332 in controls). Beta diversity highlighted BCL-specific viral heterogeneity, contrasting conserved T/NKCL viral profiles. Anelloviridae and Picobirnavirus expansion aligns with immune dysfunction, whereas NKCL-restricted HPgV-1 prevalence underscores biomarker potential. These findings implicate blood virome alterations marked by viral family predominance and diversity loss in NHL pathogenesis via immune modulation or oncogenesis. This first comprehensive NHL virome profile identifies subtype-specific signatures (Anelloviridae/Picobirnavirus/HPgV-1) for potential diagnostic and therapeutic targeting. Validation of these biomarkers may refine NHL subtyping and elucidate virome-lymphomagenesis mechanisms.