Porcine epidemic diarrhoea virus (PEDV), a pathogenic microorganism that induces epidemic diarrhoea in swine, causes substantial economic damage to swine-farming nations. To prevent and control PEDV infections, the availability of upgraded and rapid virus detection techniques is crucial. The clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein (Cas)13a system, namely, programmability of CRISPR RNA (crRNA) and "collateral" promiscuous RNase activity of Cas13a after target RNA identification. In this study, we aimed to develop a recombinase polymerase amplification (RPA)-based CRISPR-Cas13a approach for PEDV diagnosis for the first time. The results showed that up to 10 copies of the target PEDV DNA standard/µL were detected after 40 min at 37 °C. PEDV detection exhibited remarkable specificity compared to that of other selected pathogens. Additionally, this RPA-based CRISPR-Cas13a approach could be used to clinical samples, with similar performance to that of reverse transcription-quantitative polymerase chain reaction (RT - qPCR). The results of our proposed approach were visualized using either lateral flow strips or fluorescence for field-deployable viral diagnostics, thereby facilitating its use in endemic regions. Overall, our proposed approach showed good reliability, sensitivity, and specificity, suggesting that it is applicable for detecting other viruses in diagnosing diseases and inspecting food safety.

The COVID-19 pandemic and large-scale administration of multiple SARS-CoV-2 vaccines have attracted global attention to the short-term and long-term effects on the human immune system. An analysis of the "traces" left by the body's T-cell immune response is needed, especially for the prevention and treatment of breakthrough infections and long COVID-19 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant infections. T-cell receptor complementarity determining region 3 (TCR CDR3) repertoire serves as a target molecule for monitoring the effects, mechanisms, and memory of the T-cell response. Furthermore, it has been extensively applied in the elucidation of the infectious mechanism and vaccine refinement of hepatitis B virus (HBV), influenza virus, human immunodeficiency virus (HIV), and SARS-CoV. Laboratories worldwide have utilized high-throughput sequencing (HTS) and scTCR-seq to characterize, share, and apply the TCR CDR3 repertoire in COVID-19 patients and SARS-CoV-2 vaccine recipients. This article focuses on the comparative analysis of the diversity, clonality, V&J gene usage and pairing, CDR3 length, shared CDR3 sequences or motifs, and other characteristics of TCR CDR3 repertoire. These findings provide molecular targets for evaluating T-cell response effects and short-term and long-term impacts on the adaptive immune system following SARS-CoV-2 infection or vaccination and establish a comparative archive of T-cell response "traces."

is the most common pathogen in systemic fungal diseases, exhibits a complex pathogenic mechanism, and is increasingly becoming drug tolerant. Therefore, it is particularly important to study the genes associated with virulence and resistance of . Here, we identified a gene () that encodes a conserved mitochondrial protein known as , upon deletion of , the deleted strain () experienced impaired growth, hyphal development, and virulence. displayed a reduced capacity to utilize alternative carbon sources, along with detrimental alterations in reactive oxygen species (ROS), mitochondrial membrane potential (MMP) depolarization, and adenosine triphosphate (ATP) levels. Interestingly, demonstrated resistance to azole drugs, and under the influence of fluconazole, the cell membrane permeability and mitochondrial function of were less compromised than those of the wild type, indicating a reduction in the detrimental effects of fluconazole on . These findings highlight the significance of as a crucial gene for the maintenance of cellular homoeostasis. Our study is the first to document the effects of the gene on the virulence and azole resistance of at both the molecular and animal levels, providing new clues and directions for the antifungal infection and the discovery of antifungal drug targets.

Anthracnose, caused by species, induces significant economic damages to crop plants annually, especially for . During infection, the counter-defence mechanisms of plant pathogens against ROS-mediated resistance, however, remain poorly understood. By employing Weighted Gene Co-expression Network Analysis (WGCNA), we identified ACTIVATOR PROTEIN-1 (AP-1), a bZIP transcription factor, as significant to infection. And deletion of inhibited aerial hyphae formation and growth under oxidative stress. Furthermore, RNA-seq analysis post HO treatment revealed 33 significantly down-regulated genes in the AP-1 deficient strain, including A12032, a dual specificity phosphatase (DSP) homologous to MSG5 from . This Δ strain showed enhanced oxidative tolerance, reduced ROS scavenging, and negative regulation of the CWI MAPK cascade under oxygen stress, suggesting its involvement in oxidative signal transduction. Importantly, we provide evidence that CfMsg5 regulates growth, endoplasmic reticulum stress, and several unfolded protein response genes upregulated in Δ. Collectively, this study identified core components during infection and highlights a potential regulatory module involving CfAp1 and CfMsg5 in response to host ROS bursts. It provides new insights into fungal infection mechanisms and potential targets like and for managing anthracnose diseases.

The hypervirulent (hvKp) with K1 and K2 capsular types causes liver abscess, pneumonia, sepsis, and invasive infections with high lethality. The presence of capsular polysaccharide (CPS) resists phagocytic engulfment and contributes to excessive inflammatory responses. Bacteriophage depolymerases can specifically target bacterial CPS, neutralizing its defense. Based on our previous research, we expressed and purified a bacteriophage depolymerase (Dep1979) targeting hvKp with capsule type K2. Interestingly, although Dep1979 lacked direct bactericidal activity , it exhibited potent antibacterial activity . Low-dose Dep1979 (0.1 mg/kg) improved the 7-day survival of immunocompetent mice to 100%. Even at 0.01 mg/kg, mice achieved 100% survival at 5 days, although efficacy sharply declined at doses as low as 0.001 mg/kg. Following Dep1979 treatment, reduced expression of inflammatory factors and no apparent tissue damage were observed. However, therapeutic efficacy significantly diminished in immunosuppressed mice. These findings underscore the critical role of Dep1979 in disarming CPS, which synergizes with host immunity to enhance antibacterial activity against hvKp.

is an opportunistic yeast capable of causing a wide range of mucosal, cutaneous, and systemic infections. However, therapeutic strategies are limited to a few antifungal agents. Inorganic nanoparticles have been investigated as carrier systems for antifungals as potential new treatments. In this study, we focused on the antifungal activity of gold nanorods, a specific rod-shaped gold nanoparticle, produced by green synthesis using resveratrol as a metal-reducing agent. The synthesis method resulted in stable control nanoparticles (AuNp) and resveratrol-coated gold nanoparticles (AuNpRSV) with medium sizes of 32.4 × 15.9 nm for AuNp, and 33.5 × 15.3 nm for AuNpRSV. Both AuNp and AuNpRSV inhibited the grown at 2.46 µg/mL, exhibited fungicidal effects at 4.92 µg/mL, and significantly decreased filamentation, biofilm viability, reactive oxygen species production and ergosterol levels of . In addition, exposure to AuNpRSV reduced the ability of to grow in the presence of cell membrane stressors. Transmission electron microscopy revealed enlargement of the cell wall and retraction of the cell membrane after treatment with AuNp and AuNpRSV. Promisingly, toxicity analysis demonstrated that both nanoparticles maintained the full viability of larvae at 49.20 µg/mL. In conclusion, both gold nanoparticles exhibited antifungal activity; however, these effects were enhanced by AuNpRSV. Altogether, AuNps and AuNpRSVs are potential antifungal agents for the treatment of infections.

(RA) is a significant poultry pathogen causing acute septicemia and inflammation. The function of protease RAYM_01812, responsible for gelatin degradation, is unexplored in RA pathogenesis. To elucidate its role, we generated a deletion mutant ΔRAYM_01812 (ΔRAYM) and complementary CΔRAYM_01812 (CΔRAYM) strain and revealed the protease's role in extracellular gelatinase activity. By expressing full-length 76 kDa RAYM_01812 protein without signal peptide as well as seven partial structural domains fragments, we evidence that the N-terminal propeptide acts as an enzymatic activity inhibitor and it gets cleaved at A. Also, we show that the β-fold sheet domain is necessary for enhancing the enzymatic protease activity. Sequential auto-proteolysis forms a stable 40 kDa enzyme. Then, testing the strains in duck sera indicated that the absence or presence of RAYM_01812 results in reduced or enhanced bacterial survival, respectively. Furthermore, we found that the protease is able to cleave IgY antibodies as well as the complement factors C3a and C5a, that the protease reduces C3a- or C5a-mediated monocyte chemotaxis, and results in enhanced membrane attack complex (MAC) formation on the surface of ΔRAYM compared to CΔRAYM. This suggests that RAYM_01812 plays a crucial role in protecting against the serum complement-mediated bactericidal effect through inhibiting MAC formation and monocyte chemotaxis. Animal infection assays showed a 1090-fold reduced virulence of ΔRAYM compared to RA-YM, evidenced by decreased tissue loading and weaker histopathological changes. In conclusion, RAYM_01812 acts as a vital virulence factor, enabling host innate immune defence escape through complement killing evasion and monocyte chemotaxis inhibition.

Porcine reproductive and respiratory syndrome (PRRS) is associated with the endemic outbreak of fever, anorexia, and abortion in pregnant sows, resulting in an enormous economic impact on the global swine industry. Current mainstream prophylactic agents and therapies have been developed to prevent PRRSV infection; however, they have limited efficacy. Therefore, there is an urgent need to develop novel antiviral strategies to prevent PRRSV infection and transmission. The identification of new PRRSV entry mediators, such as MYH9 and HSPA8; viral apoptotic mimicry; and TIM-induced macropinocytosis, to facilitate infection has led to a novel molecular understanding of the PRRSV infection mechanism, which can be utilized in the development of prophylactic agents and therapies for PRRSV infection. Polyphenols, complex chemical molecules with abundant biological activities derived from microorganisms and plants, have demonstrated great potential for controlling PRRSV infection via different mechanisms. To explore new possibilities for treating PRRSV infection with polyphenols, this review focuses on summarizing the pathogenesis of PRRSV, reviewing the potential antiviral mechanisms of polyphenols against PRRSV, and addressing the challenges associated with the widespread use of polyphenols.

Periodontitis is one of the chronic diseases that have the greatest impact on human health, and it is associated with several other chronic diseases. Tissue damage associated with periodontitis is often connected with immune response. Immune cells are a crucial component of the human immune system and are directly involved in periodontitis during the inflammatory phase of the disease. Macrophages, as a key component of the immune system, are responsible for defence, antigen presentation and phagocytosis in healthy tissue. They are also closely linked to the development and resolution of periodontitis, through mechanisms such as macrophage polarization, pattern recognition receptors recognition, efferocytosis, and Specialized Pro-resolving Mediators (SPMs) production. Additionally, apoptosis and autophagy are also known to play a role in the recovery of periodontitis. This review aims to investigate the aforementioned mechanisms in more detail and identify novel therapeutic approaches for periodontitis.

Hepatitis B virus (HBV) infection poses a challenge to global public health. Persistent liver infection with HBV is associated with an increased risk of developing severe liver disease. The complex interaction between the virus and the host is the reason for the persistent presence of HBV and the risk of tumor development. Chronic liver inflammation, integration of viral genome with host genome, expression of HBx protein, and viral genotype are all key participants in the pathogenesis of hepatocellular carcinoma (HCC). Epigenetic regulation in HBV-associated HCC involves complex interactions of molecular mechanisms that control gene expression and function without altering the underlying DNA sequence. These epigenetic modifications can significantly affect the onset and progression of HCC. This review summarizes recent research on the epigenetic regulation of HBV persistent infection and HBV-HCC development, including DNA methylation, histone modification, RNA modification, non-coding RNA, etc. Enhanced knowledge of these mechanisms will offer fresh perspectives and potential targets for intervention tactics in HBV-HCC.

() is a foodborne intracellular pathogen that causes serious disease in both humans and animals. InlB is the major internalin protein of , which anchors to the bacterial surface and mediates its invasion into various host cells. Recent studies have shown that galactosylation of the cell wall polymer wall teichoic acid (WTA) is essential for InlB anchoring on the cell surface of serotype 4b strains. Galactosylation of WTA is exerted by the coordinated action of several glycosyltransferases, including GalU, GalE, GtcA, GttA, and GttB. Among these glycosyltransferases, GttA and GttB are specific to serotype 4b strains, whereas GalE, GalU, and GtcA are conserved across all serotypes. The role of GalE in InlB anchoring and pathogenicity remains unclear. In this study, we deleted the gene, which is involved in galactosylation, from strain ScottA. We found that deletion reduced InlB anchoring, weakened bacterial adhesion and invasion of Caco-2 cells (human colorectal adenocarcinoma cells) and MGC803 cells (human gastric carcinoma cells), increased phagocytosis but decreased proliferation in RAW264.7 cells (mouse mononuclear macrophage leukaemia cells), and decreased bacteria load, mortality, and tissue damage in infected mice. Taken together, deletion significantly reduced the anchoring of InlB and weakened the pathogenicity of . This finding provides new insights into the correlation between cell wall modification and pathogenicity of .

Liver metabolites are involved in the progression of rheumatoid arthritis (RA), indicating a connection between the liver and joints. However, the impact and mechanism of Hepatitis B virus (HBV), a hepatotropic virus, on RA are still unclear. We investigated the correlation between HBV and RA using Mendelian randomization analysis. Single-cell transcriptome analysis was conducted to investigate changes in cell subtypes in synovial tissue of HBV-RA patients. Fibroblast-like synoviocytes (FLS) were used to create a cell model, and the transcriptome was examined to identify the key downstream molecules of FMT regulated by HBx. CIA model was constructed using HBV transgenic, HBx transgenic, and TRADF1 knockout mice to investigate the impact and mechanism of HBV on CIA. The results of our study revealed a significant positive correlation between HBV and RA. The functional studies identified a crucial role of fibroblast-myofibroblast transition (FMT) in the progression of RA. The results suggest that HBV-encoded HBx may promote FMT in RA by upregulating TRAFD1. Furthermore, trans-ferulic acid (TFA) was identified by screening for common metabolites in the liver, joints, and peripheral blood using the metabolome and WGCNA. Interestingly, we found that TFA ameliorated HBx-induced RA by suppressing TRAFD1 expression. Our study demonstrates that hidden liver-joint axis, an imbalance between TFA and HBx, plays a critical role in HBV-induced RA, which could be a potential strategy for preventing RA development.

Well-intestinal health is crucial for better growth performance in pigs. Type 3 immunity, which is one of the three types of immune responses in mammals, plays a vital role in maintaining intestinal homoeostasis. Therefore, we initially introduce the type 3 immune cells in the intestine of pigs, including their distribution, development, and function. We then discuss the type 3 immune response under infection, encompassing bacterial, fungal, and viral infections. It also covers two major stresses in pigs: heat stress and weaning stress. Lastly, we discuss the effects of various nutrients and feed additives on the regulation of the type 3 immune response in pigs under infection. This review aims to contribute to the understanding of the interaction between infection and type 3 immunity in pigs and to illustrate how various nutrients modulate the type 3 immune response in pigs under diverse infections.

() is a gram-negative, spiral-shaped bacterium that colonizes the human stomach, leading to various gastric diseases. The efficacy of traditional treatments, such as bismuth-based triple and quadruple therapies, has been reduced due to increasing antibiotic resistance and drug toxicity. As a result, the development of effective vaccines was proposed to control -induced infections; however, one of the primary challenges is the lack of potent adjuvants. Although various adjuvants, both toxic (e.g. cholera toxin and heat-labile toxin) and non-toxic (e.g. aluminum and propolis), have been tested for vaccine development, no clinically favorable adjuvants have been identified due to high toxicity, weak immunostimulatory effects, inability to elicit specific immune responses, or latent side effects. Outer membrane vesicles (OMVs), mainly secreted by gram-negative bacteria, have emerged as promising candidates for vaccine adjuvants due to their potential applications. OMVs enhance mucosal immunity and Th1 and Th17 cell responses, which have been recognized to have protective effects and guarantee safety and efficacy. The development of an effective vaccine against infection is ongoing, with clinical trials expected in the future.

Herpes simplex virus type 1 (HSV-1) is a globally widespread virus that causes and associates with a wide range of diseases, including herpes simplex encephalitis, herpes simplex keratitis, and herpes labialis. The interaction between HSV-1 and the host involves complex immune response mechanisms, including recognition of viral invasion, maintenance of latent infection, and triggering of reactivation. Antiviral therapy is the core treatment for HSV-1 infections. Meanwhile, vaccine development employs different strategies and methods, and several promising vaccine types have emerged, such as live attenuated, protein subunit, and nucleic acid vaccines, offering new possibilities for the prevention of HSV-1 infection. Moreover, HSV-1 can be modified into a therapeutic vector for gene therapy and tumour immunotherapy. This review provides an in-depth summary of HSV-1 infection-associated innate and adaptive immune responses, disease pathogenesis, current therapeutic approaches, recent advances in vaccine development, and vector therapy applications for cancer treatment. Through a systematic review of multiple aspects of HSV-1, this study aims to provide a comprehensive and detailed reference for the public on the prevention, control, and treatment of HSV-1.

has infected approximately 4.4 billion individuals worldwide. The known virulence genes and the existing typing methods have not been shown to have a recognized correlation with its infectivity. The aim of this study was to elucidate the relationships among known important virulence genes, coccoid transformation, and cytotoxicity of isolated from individuals with different clinical diseases to provide guidance for the development of new virulence typing methods for .

species are facultative intracellular bacterial pathogens that cause the contagious zoonotic disease, brucellosis. spp. infect a wide range of animals, including livestock, wild animals, and marine mammals. Compared with other invasive bacterial pathogens, partial information is available on the virulence factors of that enable them to survive in the host. Here, we performed transposon-based random mutagenesis of and identified the arginine/ornithine binding protein, ArgT, as one of the crucial virulence determinants of . Deleting from or resulted in its attenuation in macrophages, which was restored upon complementation with an expression plasmid. We observed that macrophages infected with Δ produced elevated levels of NO due to the inability of these mutants to deplete the host intracellular arginine through their importer. Furthermore, defective survival of Δ and was observed in the infected mice, which correlated with enhanced NO production in the mice. Our studies revealed that plays a vital role in preventing intracellular killing and contributes to the chronic persistence of in the host. This study highlights the essential role of arginine in clearing intracellular infections and the subversion of this host defense mechanism by intracellular pathogens for their chronic persistence.

Prenyltransferases act essential roles in the prenylation modification, which is significant for proteins, like small GTPases to execute various important activities in (). The structures and partial functions of prenyltransferases (FTase, GGTase-I, and GGTase-II) in prenylation process have been dissected in . However, the cellular effects of prenyltransferases on type 2-ME49 strain of are largely unknown. To address this gap, CRISPR/Cas9-based gene-editing technology was employed to construct conditional knockdown strains of prenyltransferases in ME49 strain. Subsequent observation of ingestion ability of host cytosolic molecules (e.g, green fluorescent protein [GFP]) and status of secretory vacuolar sorting post-knockdown of prenyltransferases revealed significant findings. Our study demonstrated that degradation of FTase and GGTase-II notably affected the trafficking of endocytic GFP and vacuolar secretory trafficking to rhoptry bulb. Additionally, depletion of GGTase-II led to disordered endoplasmic reticulum and microtubules, as well as impaired gliding motility. The integrity of mitochondrion was damaged after degradation of GGTase-I. These findings underscore the critical functions of prenyltransferases in endocytosis and secretory vacuolar sorting in ME49 strain of , thereby enhancing our understanding of prenyltransferases as potential drug targets.

DNA damage repair is a crucial cellular mechanism for rectifying DNA lesions arising during growth and development. Among the various repair pathways, postreplication repair (PRR) plays a pivotal role in resolving single-stranded gaps induced by DNA damage. However, the contribution of PRR to virulence remains elusive in the fungal pathogen . In this study, we investigated the role of Rad18, a critical component of PRR, in DNA damage response and virulence in . We observed that deletion of in resulted in heightened sensitivity to DNA damage stress. Through deletion of specific internal domains coupled with spot assay analysis, we show that the internal RING and SAP domains play essential roles in DNA damage response, whereas the ZNF domain was less important. Surprisingly, the lack of Rad18 in resulted in heightened intracellular survival within macrophages and elevated virulence in the model. RNAseq analysis revealed that loss of Rad18 upregulated the transcription of genes encoding transporters and oxidoreductases, as well as virulence genes, including and . Suppression of the transcription of these virulence genes in the deletion strain by a dCas9-mediated CRISPRi system reversed this increased virulence. Taken together, these data demonstrate that Rad18 plays a significant role in virulence partially through transcriptional suppression of virulence genes and in . Our findings provide valuable insights into the intricate relationship between DNA damage response and virulence in .

is an obligate intracellular gram-negative bacterium with a unique biphasic developmental cycle. It is a zoonotic pathogen with a wide range of hosts and can cause avian chlamydiosis in birds and psittacosis in humans. The pathogen is transmitted mainly through horizontal transmission between birds. Cross-species transmission sometimes occurs and human-to-human transmission has recently been confirmed. This review provides an updated overview of from the perspective of both avian chlamydiosis and psittacosis. We include the aspects of genotype, host-pathogen interaction, transmission, epidemiology, detection and diagnosis, clinical manifestation, management, and prevention, aiming to provide a basic understanding of and offer fresh insights focused on zoonosis and cross-species transmission.