Search Results (2,393)

Streptococcus agalactiae, also known as Group B Streptococcus (GBS), is a major pathogen responsible for mastitis in dairy cows. It causes persistent and difficult-to-treat mammary infections, leading to reduced milk production. Baicalein, a flavonoid compound, exhibits anticancer, anti-inflammatory, and antibacterial activities; however, its specific mechanism of action against GBS remains unclear. This study aimed to investigate the mechanism by which baicalein inhibits GBS invasion of bovine mammary epithelial cells (bMECs). The results showed that baicalein at concentrations of 4 μg/mL or higher effectively inhibited 50% of the invasion of bMECs by GBS strain HB31 and exerted a concentration-dependent inhibitory effect on bacterial adhesion. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of baicalein against HB31 were both greater than 1024 μg/mL. Therefore, the antibacterial effect of baicalein alone may not fully account for its mechanism; other pathways likely contribute to the reduced invasiveness of GBS. To elucidate the mechanism by which baicalein inhibits GBS invasiveness, this study investigated both bacterial metabolism and gene expression. Metabolomic analysis revealed that baicalein treatment led to the downregulation of amino acid metabolites, including alanine and aspartic acid, as well as nucleotide metabolites such as adenine and UMP in GBS HB31. Additionally, the NADH/NAD⁺ ratio increased while ATP levels decreased, indicating that the overall metabolic activity of GBS was suppressed. Transcriptomic analysis focused on changes in invasion-associated virulence genes. The results showed that the expression of pbsP, an invasion-associated virulence gene, was significantly reduced, while the expression of hylB and cfb showed downward trends that did not reach statistical significance. In contrast, the expression of cylE and the two-component system vicKR was upregulated. The upregulation of cylE may be related to baicalein-induced oxidative stress in HB31. Furthermore, HB31 suppressed Nrf2-HO-1 mRNA expression, whereas baicalein activated the Nrf2 signaling pathway and reduced HB31-induced IL-6 and NF-κBmRNA expression. These findings provide new insights for the development of anti-virulence therapeutic strategies targeting GBS. Full article

Background/Objectives: Malaria remains a major global health burden, particularly in sub-Saharan Africa, where the recent invasion and urban expansion of Anopheles stephensi are increasing transmission risk in densely populated areas. Conventional vector control strategies, including widespread insecticide application, are progressively losing efficacy due to the rapid spread of resistance. These limitations have accelerated the development of genetic control approaches aimed at either suppressing vector populations or replacing them with genetically modified mosquitoes incapable of transmitting pathogens, with the shared objective of reducing disease transmission. For population suppression strategies, an essential component is a conditional regulatory system that enables precise control of toxic or otherwise deleterious effector proteins. The most widely used platform, the tetracycline-dependent (Tet) system, modulates gene expression in response to tetracycline. However, this system can exhibit leaky expression and variable regulation, which may compromise its reliability and limit its application in certain contexts. The dihydrofolate reductase (DHFR) destabilization domain (DD) system, developed in Drosophila, offers an alternative strategy for post-translational control of protein stability. In this system, proteins fused to a destabilization domain are rapidly degraded unless stabilized by the small molecule trimethoprim (TMP), enabling tight and reversible control. In Drosophila and prior reports, this system has been associated with relatively low fitness costs, although such effects have not been systematically evaluated in mosquitoes. Before adapting this system for mosquito genetic control, it is therefore essential to assess the impact of TMP exposure on key life-history traits. Methods: Here, we assessed the effects of varying TMP concentrations on mosquito development, survival, and reproductive output. Results: Our results demonstrate that low concentrations of TMP exposure had no detectable effects on immature development, adult survival, or reproductive output under the conditions tested, supporting the implementation of the DHFR-DD system in mosquitoes. Importantly, these effects were dose-dependent, with moderate to high TMP concentrations producing measurable impacts on mosquito fitness. Conclusions: These findings provide a foundational step toward the development of more precise and reliable conditional expression systems for genetic vector control, advancing innovative strategies to mitigate malaria transmission in high-risk regions. Full article

Background and Objectives: The epidemiological characteristics of Candida species have changed worldwide, with an increasing number of reports on co-infections with non-albicans Candida species (NACs) and multidrug-resistant bacteria. A longer length of hospital stay, more severely ill patients, and empirical antimicrobial use in intensive care units (ICUs) increased the prevalence of Candida healthcare-associated infections (HAIs). If the diagnosis or treatment of invasive candidiasis is delayed, the morbidity and mortality of patients will significantly increase. Materials and Methods: We conducted a nationwide surveillance study to analyze data on HAIs in the ICUs of medical centers and regional hospitals between 2018 and 2023. We assessed the temporal trends of Candida species (including Candida albicans and NACs) across all HAIs, bloodstream infections (BSIs), and urinary tract infections (UTIs), and simultaneously assessed the corresponding trends of Enterococcus faecium (Efm). A linear trend for the proportions of microorganisms from 2018 to 2023 was noted according to the Mantel–Haenszel chi-square test. Spearman’s rank correlation coefficients were used to analyze the correlations between pathogen proportions, systemic antimicrobial agent consumption, and length of ICU stay. Results: The overall proportion of all Candida species in HAIs in the ICUs increased significantly from 15.13% to 16.74% (p < 0.001); this increase was driven mainly by NACs (increasing from 6.84% to 7.91%, p < 0.001) from 2018 to 2023. The proportion of Efm increased significantly, from 7.7% to 11.11% (p < 0.001). The proportions of all Candida species significantly increased in UTIs (from 24.63% to 28.13%, p < 0.001), especially NACs, while the proportion of Efm also increased significantly in UTIs (from 9.47% to 15.32%, p < 0.001). With respect to the UTIs, the proportion of all the Candida species, C.albicans, and NACs were positively correlated with the amount of systemic antibiotics used. A longer hospital stay was strongly correlated with all Candida HAIs and UTIs, especially NACs. Significantly ecological associations between all the Candida strains and Efm were observed for UTIs. Conclusions: This study revealed that a persistent expansion of NAC infections was associated with increased Efm infections and rising antibiotic consumption. The changes in the proportions of different Candida species in UTIs were most pronounced. These findings support an ecological model in which antibiotic stress and chronic critical illness contribute to the expansion of fungal–bacterial co-infections in the ICU setting and underscore the need for integrated antibiotic management and multi-infection surveillance. Full article

Invasive alien species (IAS) not only threaten biodiversity and ecosystems but also play a significant role in the spread of infectious diseases; however, the epidemiological role of many IAS remains poorly understood. This study presents the first systematic review of major pathogens reported in 22 IAS of concern to the European Community. Given the breadth of available data, we relied on a literature search including studies reporting natural infections in target IAS, excluding experimental infections and non-target species. A total of 541 publications between 1963 and 2023 were analyzed, identifying 472 pathogens, of which 64 were classified as high-priority based on key global and European frameworks. IAS with broader distribution and higher research effort were associated with greater pathogen richness, suggesting potential epidemiological relevance but also highlighting detection bias. A composite Host–Pathogen Influence Index (HPI-IAS) revealed spatial heterogeneity in epidemiological pressure across Europe, with Poland, Germany, Italy, and France identified as areas of elevated epidemiological concern. These findings underscore the urgent need for coordinated, cross-border monitoring strategies at the European level and contribute to a broader understanding of IAS-related infectious disease ecology within a One Health framework. Full article

Infectious agents shape fish populations by inducing lethal and sublethal changes that alter nutrient metabolism and metal bioaccumulation. These shifts can manifest as changes in the ionome—the specific combination of essential and non-essential chemical elements defining the whole-body composition of an individual. Understanding how pathogens shape the fish ionome is critical for developing advanced monitoring tools and clarifying the ecological roles of hosts and their pathogens. This study reports the first documented outbreak of Citrobacter freundii, Pseudomonas aeruginosa, Pseudomonas mosselii, and Shewanella xiamenensis bacterial infections in wild-caught eastern mosquitofish (Gambusia holbrooki) from three populations in Extremadura, southwestern Spain. Under laboratory-controlled conditions, we established associations between these bacterial outbreaks and the whole-fish body ionome of G. holbrooki. We compared 19 chemical elements and seven elemental ratios among diseased fish, healthy fish at the outbreak, and individuals fully recovered 100 days post-infection following antibiotic treatment. The fish ionome clearly discriminated between diseased and healthy states, and the response was consistent across all three populations. Our findings support the utility of whole-fish body elemental composition in G. holbrooki as a biomarker for environmental monitoring. Furthermore, as the bacterial infections were associated with the capture and transport-induced stress of wild individuals, this study provides critical data on the opportunistic pathogens that may be co-introduced into recipient ecosystems through the release of this widely distributed invasive fish species. Full article

A history of invasive mold disease (IMD) often delays or contraindicates allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children. Given the limited data on pediatric patients with pre-allo-HSCT IMD, we aimed to describe the management and clinical outcomes of a cohort of children with IMD prior to allo-HSCT through day +100 post-transplantation. Between 2021 and 2024, ten pediatric patients were identified with proven or probable IMD. Their median age was 8.5 years. The most common pathogens were Aspergillus (n = 5) and Fusarium (n = 4). Infections most frequently involved the lungs followed by paranasal sinuses, bloodstream, liver, and skin. All patients demonstrated clinical improvement before transplantation, and by day +100 post-HSCT, no IMD relapses or infection-related mortality were observed. These findings suggest that complete radiologic or clinical resolution is not a prerequisite for proceeding with transplantation. Recent IMD should not be considered an absolute contraindication to urgent allo-HSCT when clinical improvement is evident, as transplantation facilitates immune reconstitution necessary for definitive infection control. Full article

Salmonella enterica infection remains a major threat to poultry health and food safety, largely due to its ability to invade the intestinal epithelium, modulate host immunity, and persist intracellularly. Curcumin, a bioactive phytochemical, has shown promising antimicrobial and immunomodulatory potential; however, its precise molecular interplay with host and pathogen systems remains unclear. An integrated computational pipeline was applied, combining target prediction, host immune network construction, Salmonella virulence interaction analysis, STRING-based PPI mapping, KEGG/GO enrichment, and molecular docking validation. Host immune hub genes and Salmonella virulence regulators were identified, followed by docking of curcumin to key host (AKT1, STAT3, TNF) and pathogen proteins (invA, phoP, ssrB). Host network analysis revealed enrichment in the PI3K–AKT, NF-κB, FoxO, and IL-10 signaling pathways, indicating roles in epithelial protection, immune regulation, inflammation suppression, and antioxidant defense. Salmonella virulence hubs were primarily associated with epithelial invasion, Type III secretion, intracellular survival, and global virulence reg-ulation. Docking analysis demonstrated a strong binding affinity of curcumin toward AKT1 (−7.4 kcal/mol), STAT3 (−6.5 kcal/mol) and TNF (−5.8 kcal/mol), supporting host immunomodulation and epithelial protection. Simultaneously, curcumin showed notable affinity for phoP (−6.8 kcal/mol), invA (−6.3 kcal/mol), and ssrB (−5.8 kcal/mol), suggesting the potential suppression of virulence signaling, invasion machinery, and intracellular persistence. This integrated host–pathogen systems analysis demonstrates that curcumin exerts a dual regulatory effect by enhancing host immune protection while concurrently disrupting Salmonella virulence mechanisms. These findings provide mechanistic insight supporting curcumin as a promising natural therapeutic candidate for controlling Salmonella infection in broilers. Full article

Environmental DNA (eDNA) offers a promising, non-invasive approach for monitoring infectious agents in aquaculture. While molecular techniques for detecting shrimp pathogens are well established in host tissues, there is a lack of standardized protocols for pathogen detection from environmental samples using conventional PCR. In this study, we developed and validated a universal conventional PCR protocol for monitoring DNA from major viral and bacterial shrimp pathogens within pond water and sediment samples. The method was applied to two commercial shrimp farms in Mexico, where eDNA was extracted from field-collected water and sediment. Using published primer sets, we successfully amplified DNA sequences corresponding to six key pathogens—Infectious hypodermal and hematopoietic necrosis virus (IHHNV), Baculovirus penaei (BP), Monodon baculovirus (MBV), Shrimp hemocyte iridescent virus (SHIV), Candidatus Hepatobacter penaei (NHP-B), and Acute hepatopancreatic necrosis disease (AHPND)-causing Vibrio spp.—in environmental samples. Sequencing of PCR amplicons confirmed 93–100% identity to previously reported pathogen strains, highlighting the method’s reliability. Pathogen detection rates varied by site, sample type, and date, with the percentage of positive samples ranging from 11.1% to 77.7%. Notably, this is the first report of SHIV DNA detection from environmental samples in the Americas, highlighting its value for pathogen surveillance even in the absence of documented outbreaks. This protocol offers a cost-effective and scalable tool for pathogen surveillance in shrimp aquaculture, enhancing early disease detection and contributing to improved biosecurity and risk assessment frameworks. Full article

Streptococcus canis is an opportunistic pathogen that colonises the mucosal surfaces and skin of its host. Though predominantly a veterinary pathogen affecting cats and dogs, S. canis has also been identified as the causative agent in severe human disease. IdeC is a secreted cysteine protease of S. canis that has a high specificity for IgG, cleaving at the hinge region. We show here that the protein binds back to the surface of the bacteria. Additionally, the protein contains a conserved Arg-Gly-Asp (RGD) motif, the minimal peptide sequence required for integrin binding. Several bacterial proteins containing RGD motifs have been implicated in adhesion and invasion of host cells. This RGD motif along with the ability of IdeC to bind back to the bacterial surface after secretion is the basis for this study into a potential secondary function of IdeC in adhesion and/or invasion. We used protein-coated latex beads to investigate the interaction of IdeC with epithelial and endothelial cells and, further, the extent to which the RGD motif is involved in this interaction by utilising an RGD->RGE recombinant protein. We also report here that the deletion of IdeC in S. canis results in a significant reduction in invasion into epithelial cells. Full article

Background: Respiratory syncytial virus (RSV) is a leading global pathogen of acute lower respiratory tract infection, posing significant risks to infants, the elderly, and immunocompromised patients. Artemisia argyi Levl.et Vant Extract (AALE) and its active components have a variety of pharmacological effects, but their anti-RSV potential remains unclear. The aim of this study is to investigate the anti-RSV activity of AALE and parthenolide and its underlying mechanisms. Methods: Cell counting kit-8 (CCK-8) assay was used to determine the anti-RSV activities of AALE and parthenolide. Time-of-addition assay and phase of action analysis were used to explore the effect of drugs on the viral replication cycle. Quantitative polymerase chain reaction (qRCR), immunofluorescence (IF) and Western blot (WB) were used to investigate the effects of AALE and parthenolide on RSV-F gene and protein and on RIG-I/TLR-3 pathway related molecules in vitro. In vivo antiviral efficacy was verified by hematoxylin–eosin (HE) staining for lung histopathology, quantitative real-time PCR (qPCR) quantification of RSV-F, RIG-I, TLR-3, IRF3, IL-6, and IFN-β gene expression in lung tissues, and enzyme-linked immunosorbent assay (ELISA) for serum IL-6 and IFN-β levels. Results: AALE exhibited the strongest anti-RSV activity among the extracts (SI = 27.6), while parthenolide was the most potent monomeric compound (SI = 8.19). In vitro, both AALE and parthenolide were effective in the co-treatment and post-treatment models, reducing RSV-F gene and F protein levels in infected cells. Furthermore, they alleviated RSV infection by regulating RIG-I and TLR-3 pathway-related genes and proteins. In vivo, AALE and parthenolide suppressed lung index and RSV proliferation, attenuated lung injury, and down-regulated RIG-I, TLR-3, IRF3, IL-6, and IFN-β expression in the lungs of RSV-infected mice. Conclusions: AALE and its component parthenolide can inhibit the invasion and replication of RSV, making it a potential candidate for the treatment of RSV-related diseases. Full article

Liver diseases, ranging from chronic hepatitis and metabolic dysfunction to cirrhosis and hepatocellular carcinoma, represent a major global public health burden. As an immune-privileged organ, the liver harbors a unique and intricate immune microenvironment, which plays a dual role in pathogen clearance and chronicity. Kupffer cells (KCs), the primary resident macrophages in the liver, constitute the first line of defense in liver innate immunity and play complex and important roles in pathogen recognition, phagocytosis, and the regulation of liver inflammation and immune responses. The complement receptor of the immunoglobulin superfamily (CRIg) is a membrane receptor that is specifically expressed on KCs. It serves not only as a sentinel for the liver against pathogen invasion but also as a sophisticated regulator for maintaining immune homeostasis. As a key component of the liver’s immune system, CRIg can efficiently mediate the clearance of complement-opsonized particles, thereby playing multidimensional roles in pathogen clearance, antigen cross-presentation, and the establishment of immune tolerance, functioning as both a “pathogen catcher” and an “immune brake.” This review focuses on the CRIg molecule, detailing its mechanisms in the recognition and phagocytic clearance by KCs, and its subsequent impact on hepatic immune responses. Furthermore, we explored the potential involvement of CRIg in the pathological progression of diverse liver diseases, including persistent inflammation, fibrosis, and hepatocarcinogenesis. This synthesis provides novel insights into the immunopathology of liver diseases and establishes a theoretical foundation for developing CRIg-targeted therapeutic strategies. Full article

Breakthrough invasive fungal infections (bIFIs) are a challenging serious complication in high-risk hematologic patients and allogeneic hematopoietic stem cell transplantation recipients that may negatively impact their outcome. Despite advances in antifungal prophylaxis, diagnostics, and supportive care, bIFI occurrence reflects a complex interaction between host immunosuppression, emergence of resistant pathogens and pharmacological variables, including subtherapeutic drug exposure. Candida spp. have shifted towards non-albicans yeasts, whereas breakthrough mold infections more frequently involve non-fumigatus Aspergillus, Mucorales, Fusarium spp., and Scedosporium/Lomentospora spp. Early clinical recognition, rapid therapy escalation, aggressive diagnostic investigation, a switch to liposomal amphotericin B-based regimens in patients on azole prophylaxis, and therapeutic drug monitoring are essential to improve outcomes. Reducing the growing global burden of bIFIs will also require improved access to high-quality diagnostics and strengthened educational and stewardship efforts that prioritize antifungal resistance as an urgent health concern. Full article

Soil-borne diseases pose a severe threat to global agricultural production and food security. Traditional chemical control methods face significant challenges, including environmental pressure, pathogen resistance, and food safety concerns. The rhizosphere microbial community, often termed the plant’s ‘second genome’, plays a pivotal role in maintaining plant health and defending against pathogen invasion. Recent advances in multi-omics technologies, synthetic microbial communities (SynComs) construction, and rhizosphere metabolomics have significantly advanced our understanding of the mechanisms by which rhizosphere microbiomes suppress soil-borne diseases. This review systematically summarizes the following: 1. key drivers of rhizosphere microbial community assembly, particularly plant “cry for help” signaling; 2. core beneficial microbial taxa and their disease-suppressive mechanisms; 3. the critical role of microbial interaction networks; 4. microbiome-based management strategies and their application progress; and 5. current challenges and future research directions. Compared with previous reviews that separately discussed rhizosphere microbiota, disease-suppressive soils, synthetic microbial communities (SynComs), or prebiotics, this review uniquely integrates multiple levels of regulation, from plant genetic determinants (‘M genes’) and root exudate-mediated ‘crying for help’ to microbiome engineering (SynComs and prebiotics) and cross-kingdom interactions (bacteria–fungi–protists–phages). A central conceptual axis of ‘M genes → microbiome engineering → breeding’ is proposed, bridging plant genetics, microbial ecology, and crop improvement for durable disease suppression. Ultimately, this work aims to provide a theoretical foundation for developing efficient and sustainable green control technologies against soil-borne diseases. Full article

Breast cancer remains the most frequently diagnosed malignancy in women worldwide, accounting for approximately 2.3 million new cases and 670,000 deaths annually. The diagnostic landscape has undergone a paradigm shift over the past two decades, evolving from morphology-based classification toward molecularly informed, precision-guided strategies. Early and accurate diagnosis is fundamental to improving outcomes; advances in imaging technology, including digital breast tomosynthesis (DBT), contrast-enhanced mammography (CEM), and abbreviated magnetic resonance imaging (MRI), have improved sensitivity and specificity in diverse patient populations. Simultaneously, the integration of artificial intelligence (AI) and radiomics into screening workflows offers unprecedented potential for risk stratification and a reduction in false-positives. At the pathological level, multi-gene expression profiling assays such as Oncotype DX, MammaPrint, Prosigna, and EndoPredict have refined prognostic classification and guide adjuvant chemotherapy decisions in early-stage hormone receptor-positive disease. The emergence of liquid biopsy, circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and exosomal biomarkers provides minimally invasive tools for real-time monitoring of response, residual disease, and the evolution of resistance mechanisms. Precision diagnostics now encompass next-generation sequencing (NGS)-based comprehensive genomic profiling, enabling identification of actionable alterations such as PIK3CA mutations, HER2 amplification, BRCA1/2 pathogenic variants, and NTRK fusions, each linked to approved therapeutic agents. The purpose of this review is to provide a comprehensive synthesis of current and emerging diagnostic modalities in breast cancer—from population-level screening to individualized molecular profiling—and to examine how integrative, multimodal diagnostic platforms are reshaping clinical decision-making in the era of precision medicine. Full article

Background/Objectives: Several trials have highlighted the importance of PARP inhibitors (PARPi) in the treatment of BRCA-associated breast cancers (BC), initiating changes in practice. However, data on the real-life outcomes of PARPi therapy is limited. In this study, we characterized the clinical characteristics and outcomes of patients with advanced BC and germline BRCA pathogenic variants (PVs) who received PARPi therapy. Methods: We conducted a retrospective single-institution cohort study of patients with advanced BC and germline BRCA1/2 PVs treated with PARPi. Outcomes included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Survival was estimated using Kaplan–Meier methods, and prognostic factors were evaluated using Cox regression analysis. Results: Of the 107 patients treated with PARPi, 48 (44.9%) and 59 (55.1%) had BRCA1 and BRCA2 PVs, respectively. Ninety-seven patients (90.7%) had invasive ductal carcinoma and 42 (39.3%) had triple-negative BC. Nineteen (17.8%) patients had de novo metastatic BC. Sixty-two (57.9%) patients received at least one line of systemic therapy before PARPi; 24 (22.4%) patients received prior platinum. ORR was 62.6%, and the median duration of response (DoR) was 7 months (range, 2.1–96.2). The median PFS was 9 months (95% CI, 6.9–10.5) and median OS was 25.8 months (95% CI, 18.7–31.5). In multivariable models for PFS, bone metastases (HR = 2.25; 95% CI, 1.40–3.61; p = 0.0008) and lung metastases (HR = 2.40; 95% CI, 1.45–3.98; p = 0.0007) were independently associated with increased risk of progression or death. In multivariable models for OS, brain metastases (HR = 3.54; 95% CI, 1.59–7.90; p = 0.0020), bone metastases (HR = 2.22; 95% CI, 1.27–3.88; p = 0.0050), and lung metastases (HR = 2.38; 95% CI, 1.38–4.11; p = 0.0018), were independently associated with increased risk of death. Conclusions: The clinical outcomes of our real-world patients are similar to those reported in previous clinical trials. In addition, metastatic site distribution was independently prognostic for survival outcomes and may support baseline risk stratification at the time of PARPi initiation. Further studies of predictive markers of response and resistance, as well as sequencing with platinums and combinations with other targeted agents, are needed to optimize the benefits of PARPi in this patient population. Full article