Virulence最新文献

Honey bees are important pollinators in both agriculture and ecosystems, and their health is essential for sustainable human development. Although only two bacteria, Paenibacillus larvae and Melissococcus plutonius, have been identified as bacterial pathogens in honey bee brood for over 100 years, we found three additional Paenibacillus strains (Paenibacillus sp. J27TS7, Paenibacillus azoreducens J34TS1, and Paenibacillus melissococcoides J46TS7) in honey that harmed honey bee brood development. In particular, Paenibacillus sp. J27TS7 was highly virulent in bee larvae (the median lethal dose [LD₅₀] = 12.7 spores/larva) and was comparable to P. larvae (LD₅₀ = 2.3-11.5 spores/larva). Paenibacillus azoreducens J34TS1 showed the second-highest virulence (LD₅₀ = 45.9 spores/larva), and P. melissococcoides J46TS7 was the least virulent (LD₅₀ = 469.0 spores/larva). However, P. melissococcoides was most frequently detected in Japanese honey among the three species, with the highest concentration being 1.8 × 10⁶ spores/mL honey, suggesting its wide distribution in Japanese apiaries. The novel pathogenic Paenibacillus species were categorized into the fast killer (Paenibacillus sp. J27TS7), medium-fast killer (P. melissococcoides), and slow killer (P. azoreducens) like P. larvae strains in terms of the time to kill infected brood; however, histopathological and genome analyses indicated that their pathogenic mechanisms were different from those of P. larvae strains. Moreover, P. melissococcoides showed differences in virulence depending on the lineage of the strain. These findings represent the first discovery of honey bee brood pathogens in more than 100 years and indicate the need to look beyond known pathogens for a comprehensive understanding of honey bee diseases.

Many factors involved in heparan sulfate (HS) biosynthesis and metabolism have been reported to play roles in viral infection. However, the detailed mechanisms are still not fully understood. In this study, we report that exostosin glycosyltransferase 1 (EXT1), the HS polymerase, is a critical regulatory factor for Zika virus (ZIKV) infection. Knocking out EXT1 dramatically restricts ZIKV infection, which is not due to the inhibition of virus entry resulting from HS deficiency, but mediated by the downregulation of autophagy. Induction of autophagy promotes ZIKV infection, and attenuated autophagy is found in distinct EXT1 knockout (EXT1-KO) cell lines. Induction of autophagy by rapamycin can relieve the ZIKV production defect in EXT1-KO cells. While over-expressing EXT1 results in the reduction of ZIKV production by targeting the viral envelope (E) protein and non-structural protein NS3 in a proteasome-dependent degradation manner. The different roles of EXT1 in ZIKV infection are further confirmed by the data that knocking down EXT1 at the early stage of ZIKV infection represses viral infection, whereas the increase of ZIKV infection is observed when knocking down EXT1 at the late stage of viral infection. This study discovers previously unrecognized intricate roles of EXT1 in ZIKV infection.

Mpox, is a zoonotic disease caused by the monkeypox virus and is primarily endemic to Africa. As countries gradually stop smallpox vaccination, resistance to the smallpox virus is declining, increasing the risk of infection with mpox and other viruses. On 14 August 2024, the World Health Organization announced that the spread of mpox constituted a public health emergency of international concern. Mpox's transmission routes and symptoms are complex and pose new challenges to global health. Several vaccines (such as ACAM2000, JYNNEOS, LC16m8, and genetically engineered vaccines) and antiviral drugs (such as tecovirimat, brincidofovir, cidofovir, and varicella immunoglobulin intravenous injection) have been developed and marketed to prevent and control this disease. This review aims to introduce the epidemic situation, epidemiological characteristics, physiological and pathological characteristics, and preventive measures for mpox in detail, to provide a scientific basis for the prevention and control of mpox viruses worldwide.

Uncontrolled immune responses resulting from overactivated cellular signaling pathways, leading to inflammation and tissue injury, are a major cause of death in pathogen-infected individuals. This phenomenon has been well studied in mammals but is less explored in invertebrates. Bacteria of the genus Vibrio are among the most harmful pathogens to humans and aquatic animals. In shrimp, Vibrio infection is generally characterized by the sudden onset of disease, with pathological signs of opaque and whitish muscle tissue. The current study shows that shrimp acutely infected with high dose of Vibrio parahaemolyticus develop inflammation-like pathological changes, leading to rapid death. Excessive activation of JAK-STAT signaling, rather than the Dorsal and Relish pathways, results in overactivation of shrimp immunity and is a major cause of inflammation induced by acute Vibrio infection. Weakening JAK-STAT signaling attenuates the inflammatory response and reduces mortality caused by acute Vibrio infection in shrimp, whereas enhancing JAK-STAT signaling can convert a normal infection into an acute one, accelerating shrimp death. Therefore, this study indicates that, similar to that in mammals, the pathogenesis of infectious diseases in invertebrates is complicated by inflammatory responses triggered by dysregulated immune signaling.

Sulfur metabolism is an essential aspect of fungal physiology and pathogenicity. Fungal sulfur metabolism comprises anabolic and catabolic routes that are not well conserved in mammals, therefore is considered a promising source of prospective novel antifungal targets. To gain insight into Aspergillus fumigatus sulfur-related metabolism during infection, we used a NanoString custom nCounter-TagSet and compared the expression of 68 key metabolic genes in different murine models of invasive pulmonary aspergillosis, at 3 time-points, and under a variety of in vitro conditions. We identified a set of 15 genes that were consistently expressed at higher levels in vivo than in vitro, suggesting that they may be particularly relevant for intrapulmonary growth and thus constitute promising drug targets. Indeed, the role of 5 of the 15 genes has previously been empirically validated, supporting the likelihood that the remaining candidates are relevant. In addition, the analysis of gene expression dynamics at early (16 h), mid (24 h), and late (72 h) time-points uncovered potential disease initiation and progression factors. We further characterized one of the identified genes, encoding the cytosolic serine hydroxymethyltransferase ShmB, and demonstrated that it is an essential gene of A. fumigatus, also required for virulence in a murine model of established pulmonary infection. We further showed that the structure of the ligand-binding pocket of the fungal enzyme differs significantly from its human counterpart, suggesting that specific inhibitors can be designed. Therefore, in vivo transcriptomics is a powerful tool for identifying genes crucial for fungal pathogenicity that may encode promising antifungal target candidates.

This review summarizes key virulence factors associated with group B Streptococcus (GBS), a significant pathogen particularly affecting pregnant women, fetuses, and infants. Beginning with an introduction to the historical transition of GBS from a zoonotic pathogen to a prominent cause of human infections, particularly in the perinatal period, the review describes major disease manifestations caused by GBS, including sepsis, meningitis, chorioamnionitis, pneumonia, and others, linking each to specific virulence mechanisms. A detailed exploration of the genetic basis for GBS pathogenicity follows, emphasizing the roles of capsules in pathogenesis and immune evasion. The paper also examines the molecular structures and functions of key GBS surface proteins, such as pili, serine-rich repeat proteins, and fibrinogen-binding proteins, which facilitate colonization and disease. Additionally, the review discusses the significance of environmental sensing and response systems, like the two-component systems, in adapting GBS to different host environments. We conclude by addressing current efforts in vaccine development, underscoring the need for effective prevention strategies against this pervasive pathogen.

The high-osmolarity glycerol (HOG) signalling pathway, comprising Ste11/Ssk2/Ssk22 (MAPKKK), Pbs2 (MAPKK), and Hog1 (MAPK), is an important and conserved pathway in fungi. However, the functions and downstream regulatory factors of Hog1 in nematode-trapping (NT) fungi remain poorly understood. Here, three proteins (AoNmd5, AoPyp1, and AoPtp) interacting with Hog1 were screened in a representative NT fungus Arthrobotrys oligospora using yeast screening library and verified using yeast two-hybrid (Y2H) assay. The function of AoNmd5 was furtherly characterized by phenotypic comparison, staining technique, and multi-omics analyses. AoNmd5 was essential for vegetative growth, conidial development, trap morphogenesis, and nematode predation ability. In addition, AoNmd5 played crucial roles in endocytosis, lipid metabolism, reactive oxygen species, stress response, autophagy, and other metabolic processes. Furthermore, we constructed an AoNmd5 interaction network based on transcriptomic analysis and Y2H, revealing its significant role in the respiratory chain and redox processes as well as its interaction with the small GTPase Ran1, which mediates Hog1 nucleocytoplasmic shuttling. These findings suggest that the Hog1-Nmd5 signalling pathway has pleiotropic roles in A. oligospora. This study deepens our understanding of the HOG pathway and its interaction with importins in NT fungi.

Infection with Helicobacter pylori is one of the most common infections of mankind. Infection typically occurs in childhood and persists for the lifetime of the host unless eradicated with antimicrobials. The organism colonizes the stomach and causes gastritis. Most infected individuals are asymptomatic, but infection also causes gastric and duodenal ulceration, and gastric cancer. H. pylori possesses an arsenal of virulence factors, including a potent urease enzyme for protection from acid, flagella that mediate motility, an abundance of outer membrane proteins that can mediate attachment, several immunomodulatory proteins, and an ability to adapt to specific conditions in individual human stomachs. The presence of a type 4 secretion system that injects effector molecules into gastric cells and subverts host cell signalling is associated with virulence. In this review we discuss the interplay of H. pylori colonization and virulence factors with host and environmental factors to determine disease outcome in infected individuals.

This study investigated the pathogenic mechanisms of Aeromonas veronii in macrophages. THP-1 derived macrophages were used as a human macrophage model and were treated with A. veronii strain AS1 isolated from intestinal biopsies of an IBD patient, or Escherichia coli strain K-12. RNA was extracted and subjected to RNA sequencing and comparative transcriptomic analyses. Protein levels of IL-8, IL-1β, IL-18, and TNFα were measured using ELISA, and apoptosis was assessed using caspase 3/7 assays. Both A. veronii AS1 and E. coli K-12 significantly upregulated the expression of many genes involving inflammation. At the protein level, A. veronii AS1 induced significantly higher levels of IL-8, TNFα, mature IL-18 and IL-1β than E. coli K-12, and led to greater elevation of caspase 3/7 activities. Both A. veronii AS1 and E. coli K-12 upregulated the expression of CASP5, but not other caspase genes. A. veronii AS1 significantly downregulated the expression of 20 genes encoding histone proteins that E. coli K-12 did not. The more profound pathogenic effects of A. veronii in inducing inflammation and apoptosis in macrophages than E. coli K-12 are consistent with its role as a human enteric pathogen. The upregulated expression of CASP5 and increased release of IL-1β and IL-18 support the role of CASP5 in activation of non-canonical inflammasome. The downregulation of histone genes by A. veronii suggests a unique impact on host cell gene expression, which may represent a novel virulence strategy. These findings advance the understanding of pathogenic mechanisms of the emerging human enteric pathogen A. veronii.

Oxalic acid (OA), an essential pathogenic factor, has been identified in several plant pathogens, and researchers are currently pursuing studies on interference with OA metabolism as a treatment for related diseases. However, the metabolic route in Magnaporthe oryzae remains unknown. In this study, we describe D-erythroascorbic acid-mediated OA synthesis and its metabolic and clearance pathways in rice blast fungus. By knocking out the D-arabino-1,4-lactone oxidase gene (Moalo1), one-third of oxalic acid remained in M. oryzae, indicating a main pathway for oxalic acid production. M. oryzae OxdC (MoOxdC) is an oxalate decarboxylase that appears to play a role in relieving oxalic acid toxicity. Loss of Mooxdc does not affect mycelial growth, conidiophore development, or appressorium formation in M. oryzae; however, the antioxidant and pathogenic abilities of the mutant were enhanced. This is owing to Mooxdc deletion upregulated a series of OA metabolic genes, including the oxalate oxidase gene (Mooxo) and Moalo1, as well as both OA transporter genes. Simultaneously, as feedback to the tricarboxylic acid (TCA) cycle, the decrease of formic acid in ΔMooxdc leads to the reduction of acetyl-CoA content, and two genes involved in the β-oxidation of fatty acids were also upregulated, which enhanced the fatty acid metabolism of the ΔMooxdc. Overall, this work reveals the role of OA in M. oryzae. We found that OA metabolism was mainly involved in the growth and development of M. oryzae, OA as a byproduct of D-erythroascorbic acid after removing H₂O₂, the OA-associated pathway ensures the TCA process and ATP supply.