Search Results (2,120)

Fusarium crown rot, a widespread and destructive disease affecting cereal crops (particularly wheat and barley), is primarily caused by the soil-borne fungal pathogen Fusarium pseudograminearum. Secondary metabolites (SMs) play a crucial role in colonization and host tissue invasion by pathogenic fungi. In this study, we investigated the functional role of FpTox2, a secondary metabolite-related gene in F. pseudograminearum. An FpTox2 deletion mutant exhibited significantly reduced radial growth compared to wild-type F. pseudograminearum. Notably, the mutant strain completely lost conidiation capacity under induced conditions. Furthermore, although it showed decreased sensitivity to the cell membrane inhibitor sodium dodecyl sulfate (SDS), the mutant demonstrated enhanced susceptibility to NaCl, a metal ion stressor. Most importantly, the pathogen’s virulence was markedly attenuated in wheat stem base infections following FpTox2 deletion, and we demonstrated that FpTox2 regulates pathogen virulence by influencing deoxynivalenol production. In conclusion, FpTox2 is crucial for vegetative growth, asexual development, abiotic stress responses, and full virulence in F. pseudograminearum. Full article

Invasive infections caused by rare moulds (RM) are increasingly reported and often exhibit resistance to antifungal agents. Their epidemiology varies regionally, yet data from Greece are scarce. To address this gap, we conducted a 15-year retrospective study of RM fungaemia at a tertiary academic hospital in Athens, Greece. All microbiologically confirmed cases in hospitalised patients between 2010 and 2024 were reviewed. Demographic and clinical data were retrieved from medical records. Incidence rates were calculated per 1000 admissions and 10,000 bed-days. Isolates were morphologically identified and, when available, molecularly characterised and tested for antifungal susceptibility according to EUCAST guidelines. Eight RM fungaemia episodes (0.8% of total fungaemias) were identified, with an incidence of 0.01/1000 admissions and 0.03/10,000 bed-days, without bacterial co-infections. Haematological malignancies (62%) were the most common underlying condition. Fusarium spp. were the predominant pathogens (6/8), followed by single cases due to Lomentospora prolificans and Acremonium spp. Amphotericin B showed the highest in vitro activity against Fusarium isolates (MIC 0.5–1 mg/L), followed by voriconazole (MICs 2–8 mg/L) whereas other azoles showed no in vitro activity (MICs ≥ 8 mg/L). Half of the infections were breakthrough, whereas in 3/8 cases, the diagnosis was established post-mortem (n = 2) or post-discharge. Among the five patients who received treatment, the crude mortality rate was 60%. This first epidemiological report on RM fungaemia in Greece highlights the predominance of Fusarium spp., the frequency of breakthrough infections, and the challenges in early diagnosis and management. Increased clinical awareness and regional surveillance are essential for optimising outcomes. Full article

Background: Hematopoietic cell transplantation (HCT) and chimeric antigen receptor T-cell (CAR-T) therapy have markedly improved survival in pediatric patients with hematological malignancies. However, these treatments cause profound immunosuppression, leading to significant susceptibility to vaccine-preventable diseases (VPDs), including invasive pneumococcal disease and measles. Timely and tailored immunization strategies are crucial to mitigate infectious risks in this vulnerable population. Methods: We conducted a narrative review of the English-language literature from 2000 to 2024, including clinical guidelines, surveys, and original studies, to evaluate immune reconstitution and vaccination practices in pediatric patients undergoing HCT and CAR-T therapy. Literature searches in PubMed, Scopus, and Web of Science used disease-specific, therapy-specific, and pathogen-specific terms. Data synthesis focused on vaccine schedules, immune recovery markers, and adherence challenges. Results: Profound immune deficits post-HCT and CAR-T therapy compromise both innate and adaptive immunity, often necessitating revaccination. Key factors influencing vaccine responses include time since therapy, graft source, immunosuppressive treatments, and chronic graft-versus-host disease. Although inactivated vaccines are generally safe from three to six months post-HCT, live vaccines remain contraindicated until documented immune recovery. CAR-T therapy introduces unique challenges due to prolonged B-cell aplasia and hypogammaglobulinemia, leading to delayed or reduced vaccine responses. Despite established guidelines, real-world adherence to vaccination schedules remains suboptimal, driven by institutional, logistic, and patient-related barriers. Conclusions: Effective vaccination strategies are essential for reducing infectious morbidity in pediatric HCT and CAR-T recipients. Personalized vaccine schedules, immune monitoring, and multidisciplinary coordination are critical to bridging gaps between guidelines and practice, ultimately improving long-term outcomes for immunocompromised children. Full article

Aspergillus fumigatus is an opportunistic filamentous fungus that primarily affects the respiratory tract of the human body. Depending on its host’s immune response, the pathogen can cause invasive pulmonary aspergillosis (IPA). Biofilm formation by A. fumigatus increases virulence and resistance against antifungals and immune response and is one important factor in IPA development. Here, two human-like models, precision cut lung slices (PCLS) and a biofilm co-culture model, have been developed to test the anti-biofilm activity of voriconazole, amphotericin B, as well as luliconazole against A. fumigatus. In both assays, metabolically active A. fumigatus biofilms were examined at different biofilm developmental stages using an XTT assay. A decrease in the metabolic activity of the fungal biofilms was detected for each of the tested agents in both assays. Significant anti-biofilm effects exist against early-stage biofilm in the co-culture model. In the PCLS assay, amphotericin B showed the strongest inhibition after 24 h. In conclusion, the applied PCLS ex vivo model can be used to study the property and activity of certain antifungal compounds against Aspergillus biofilm. With its close resemblance to human conditions, the PCLS model has the potential for improving the current understanding of biofilm treatments in laboratory settings. Full article

The velvet complex is a master regulator of multiple physiological processes in filamentous fungi. In this study, we characterized the functions of velvet gene FpvelC in Fusarium proliferatum, which was the causative agent of rice spikelet rot disease. Compared with the wild-type Fp9 strain, deletion of FpvelC hindered conidiation, leading to a low level of trehalose content but excessive accumulation of chitin in conidia. Lack of FpvelC resulted in increased sensitivity to oxidative stress and decreased expression of antioxidant genes. Notably, ΔFpvelC exhibited attenuated pathogenicity on rice and maize, failure to produce invasive hyphae, and downregulation of genes encoding xylanases and xyloglucanases during infection processes. Nevertheless, disruption of FpvelC enhanced production of fumonisin B1 (FB1) and fusaric acid concomitantly; transcripts of the clustering genes responsible for the two mycotoxins’ biosynthesis were significantly increased. Additionally, the absence of FpvelC was displayed as more sensitive to rapamycin than the Fp9 strain, accompanied with less intracellular glutamine. Overall, FpvelC played versatile roles in conidiation, response to oxidative stress, pathogenicity and mycotoxins production in F. proliferatum. Full article

Staphylococcus aureus is a leading cause of skin and soft tissue infections (SSTIs), yet the bacterial genomic adaptations underlying the transition from nasal colonization to invasive infection remain incompletely defined. We sequenced and analyzed 157 S. aureus isolates (126 from SSTIs and 31 from asymptomatic nasal colonization) from a primary care network in South Texas. Using genome-wide association studies, non-synonymous single-nucleotide variant (NSNV) profiling, and machine learning, we identified strain-specific adaptations in metabolic and regulatory pathways. SSTI isolates exhibited significant enrichment of nitrogen assimilation, purine biosynthesis, menaquinone production, and anaerobic respiration genes. Elevated copy number and colocalization of phage-linked metabolic genes—including nirB, narH, and nifR3—suggest a pathoadaptive genomic island supporting infection-specific energy generation. The enrichment of α/β-hydrolase domain-encoding genes was associated with clinical severity. To quantify severity, we developed the Purulent Ulcer Skin (PUS) score, which integrates wound size, drainage, and erythema. The α/β-hydrolase and lipoprotein genes were significantly associated with higher PUS scores (higher SSTI severity) and phage-encoded virulence gene products were linked to larger wound size. Machine learning prioritized purL and other metabolic loci as key infection classifiers. NSNVs and unitig-level changes co-localized within nutrient transport, stress resistance, and cytolytic genes, supporting a model of multi-layered genomic selection. Metagenomic assemblies of nasal microbiota were enriched for Staphylococcus, Enterococcus, and Micrococcus species, core metabolic pathways, and taxon-specific virulence determinants. This underscores the roles of metabolic and virulent co-networks within nasal commensals and their adaptive capacity for pathogenic transition. These findings provide a potential genomic blueprint of S. aureus pathoadaptation during SSTI and are a step towards the development of novel therapeutic targets. Full article

Until recently, Stenotrophomonas maltophilia was considered a low-virulence pathogen, usually found as an environmental commensal and colonizer of moist abiotic surfaces. Lately, it has increasingly been implicated in invasive infections with high associated morbidity and mortality. Most epidemiological studies involving patients with S. maltophilia infections have recorded risk factors and their associations with outcomes in critically ill patients. The aim of this study was to investigate its epidemiology as a pathogen in patients hospitalized in medical wards and potential factors associated with mortality. For this purpose, S. maltophilia-positive cultures from patients admitted to medical wards from 1 January 2023 to 30 June 2025 were collected, demographics and patient characteristics were recorded and analyzed and associated with clinical outcome. Twenty-nine patients and their first positive S. maltophilia positive culture were included in the study with a direct attributable mortality of 27.6%. Patients with cardiovascular and chronic obstructive pulmonary disease more commonly developed respiratory tract infections. Among the recorded comorbidities, only diabetes was associated with worse outcome. Most of the strains retained sensitivity to co-trimoxazole and levofloxacin and treatment outcome was not affected by the choice of regimen. This study highlights the rise of S. maltophilia to a true pathogen affecting immunocompetent patients; in combination with its antimicrobial resistance, this justifies its recognition as an emerging pathogen of public health concern. Full article

pH-sensitive intelligent films offer a novel strategy for real-time monitoring of food freshness via visible color changes. This study valorizes onion peel powder (OPP), a polyphenol-rich agro-industrial by-product, by incorporating it into cassava starch-based films at three concentrations (1O, 2O, 3O). Increasing OPP content led to significantly higher total phenolic and flavonoid levels, enhancing the films’ antioxidant properties (p < 0.0001). While the films exhibited selective antibacterial effects, pronounced inhibition zones were observed against Pseudomonas aeruginosa and Escherichia coli, two relevant meat spoilage and pathogenic bacteria. The films displayed clear and gradual color shifts from light to dark brown across a wide pH range (1–13), confirming their suitability as pH indicators. When applied as labels in minced beef packaging stored at 4 °C, the films successfully tracked freshness over 13 days. Film color changes were strongly correlated with microbial load and pH variations, accurately flagging spoilage onset. These findings support the potential of cassava starch/OPP films as biodegradable, cost-effective intelligent packaging tools, contributing to food safety, waste reduction, and circular bioeconomy principles. The system provides a practical, non-invasive solution for meat freshness monitoring without requiring instrumentation. Full article

The genus Aspergillus, widely distributed across natural and urban environments, may cause allergies and opportunistic infections such as chronic or invasive pulmonary aspergillosis. Its high pathogenic potential for immunocompromised patients, together with the alarming increase of azole resistance reported in clinical and environmental isolates, claims urgent actions to assess and control the Aspergillus community in hospital environments. To contribute to that, here, we combine a large environmental survey covering numerous air and surface samples from different zones of three hospitals in Spain, with an integrated approach including general and selective culture- and eDNA-based analyses. Despite the high prevalence of Aspergillus observed, present in almost all indoor zones (mostly in air but also on surfaces) of the three hospitals, its relative abundance in the whole fungal community was limited and dependent on the used methods, with median values ranging from 1.4% (eDNA data) and 6.8% (cultivation at 28 °C) to 28.3% (cultivation at 37 °C). Remarkably, the most protected zones (intensive care units) showed the highest proportion of Aspergillus eDNA sequences. A total of 32 species belonging to 10 Aspergillus sections were molecularly identified, including well-known causal agents of invasive pulmonary infections such as A. fumigatus, A. flavus, A. terreus, A. niger, A. oryzae, A. sydowii, and A. tubingensis. This highlights the importance of such environmental assessments for monitoring and controlling the fungal burden in hospitals. Full article

Background and purpose: Vulvovaginal candidiasis (VVC), caused by Candida albicans (C. albicans), is exacerbated by oxidative stress and uncontrolled inflammation. Pathogens like C. albicans generate reactive oxygen species (ROS) to enhance virulence, while host immune responses further amplify oxidative damage. This study investigates the antioxidant and antifungal properties of Hyssopus cuspidatus Boriss volatile extract (SXC), a traditional Uyghur medicinal herb, against fluconazole-resistant VVC. We hypothesize that SXC’s bioactive volatiles counteract pathogen-induced oxidative stress while inhibiting fungal growth and inflammation. Methods: GC-MS identified SXC’s major bioactive components, while broth microdilution assays determined minimum inhibitory concentrations (MICs) against bacterial/fungal pathogens, and synergistic interactions with amphotericin B (AmB) or fluconazole (FLC) were assessed via time–kill kinetics. Anti-biofilm activity was quantified using crystal violet/XTT assays, and in vitro studies evaluated SXC’s effects on C. albicans-induced cytotoxicity (LDH release in A431 cells) and inflammatory responses (cytokine production in LPS-stimulated RAW264.7 macrophages). A murine VVC model, employing estrogen-mediated pathogenesis and intravaginal C. albicans challenge, confirmed SXC’s in vivo effects. Immune modulation was assessed using ELISA and RT-qPCR targeting inflammatory and antioxidative stress mediators, while UPLC-MS was employed to profile metabolic perturbations in C. albicans. Results: Gas chromatography-mass spectrometry identified 10 key volatile components contributing to SXC’s activity. SXC exhibited broad-spectrum antimicrobial activity with MIC values ranging from 0.125–16 μL/mL against bacterial and fungal pathogens, including fluconazole-resistant Candida strains. Time–kill assays revealed that combinations of AmB-SXC and FLC-SXC achieved sustained synergistic bactericidal activity across all tested strains. Mechanistic studies revealed SXC’s dual antifungal actions: inhibition of C. albicans hyphal development and biofilm formation through downregulation of the Ras1-cAMP-Efg1 signaling pathway, and attenuation of riboflavin-mediated energy metabolism crucial for fungal proliferation. In the VVC model, SXC reduced vaginal fungal burden, alleviated clinical symptoms, and preserved vaginal epithelial integrity. Mechanistically, SXC modulated host immune responses by suppressing oxidative stress and pyroptosis through TLR4/NF-κB/NLRP3 pathway inhibition, evidenced by reduced caspase-1 activation and decreased pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). Conclusions: SXC shows promise as a broad-spectrum natural antimicrobial against fungal pathogens. It inhibited C. albicans hyphal growth, adhesion, biofilm formation, and invasion in vitro, while reducing oxidative and preserving vaginal mucosal integrity in vivo. By disrupting fungal metabolic pathways and modulating host immune responses, SXC offers a novel approach to treating recurrent, drug-resistant VVC. Full article

Malignant giant cell tumor of bone (GCTB) is a rare malignant bone tumor. This analysis was conducted on patients with malignant GCTB at our center. The clinical, demographic, and prognostic characteristics were evaluated and compared. During 1 January 2015 to 31 December 2022, fifty patients were included in the study, which made up 3.3% of the contemporary GCTB patients. The clinical characteristics were comparable between the 24 patients with primary malignant GCTB (PMGCTB) and 26 patients with secondary malignant GCTB (SMGTCB). The tumor location was mainly at the axial and pelvic region (70%) and differed between the two types (p = 0.040). H3F3A pathogenic variant presented frequently in SMGCTB (p = 0.020). Cox regression analysis showed the prognostic outcomes were poor in those with a tumor located in the axial bone and sacrum with invasion of other places. H3F3A mutation status is also a risk factor, while chemotherapy and denosumab failed to demonstrate prognostic benefits. Malignant GCTB is a rare condition with a poor prognosis, especially in SMGTCB. The location and H3F3A mutation status had an influence on prognosis, and systemic therapy should be taken into consideration for patients with unfavorable prognostic features. Full article

Listeria monocytogenes is a Gram-positive bacterial species that causes listeriosis, a major foodborne disease worldwide. The virulence factor inlA facilitates the invasion of L. monocytogenes into intestinal epithelial cells expressing E-cadherin receptors. Naturally occurring premature stop codon (PMSC) mutations in inlA have been shown to result in the production of truncated proteins associated with attenuated virulence. Moreover, different L. monocytogenes strains contain distinct inlA variants. In this study, we first characterized inlA in 546 L. monocytogenes strains isolated from various foods in Shanghai. The results showed that 36.1% (95% Confidence Interval: 32.0~40.2%) of the food isolates harbored inlA with PMSC, which was found to be associated with clonal complex (CC) types, with the highest proportions observed in CC9 and CC121. To investigate the function of inlA, we first used the dominant CC87 isolated from patients as the test strain and constructed an inlA-deleted strain via homologous recombination. Resistance tests and virulence tests showed that while inlA did not affect the resistance of L. monocytogenes, it significantly influenced cell adhesion and invasiveness. To further explore the function of inlA, we performed virulence tests on five CC-type strains carrying inlA with PMSC and their corresponding strains with intact inlA. We found that the virulence of L. monocytogenes strains carrying inlA or inlA with PMSC was associated with their CC type. Our preliminary results showed that premature termination of inlA did not significantly affect the adhesion and invasion abilities of low-virulence CC-type L. monocytogenes strains in Caco-2 cells, but substantially promoted those of high-virulence strains such as CC8 and CC7. In summary, this study preliminarily evaluated the effects of inlA integrity and PMSC mutation variation on the virulence of L. monocytogenes, providing a foundation for further research on inlA-related pathogenic mechanisms. Full article

Pathogenic bacteria have developed different ways to cause infections. One strategy involves using components from host cells. This study looks at the role of the cytoskeleton in the human colon adenocarcinoma Caco-2 and neonatal non-transformed epithelial H4 cell lines during bacterial invasion. The bacteria studied include Cronobacter malonaticus, Cronobacter sakazakii, and E. coli K1, as they are associated with known diseases. Salmonella enteritidis 358 served as a positive control and E. coli K12 as a negative control for the invasion experiments. Before the invasion experiments, cell lines were treated with microfilament inhibitors, specifically Cytochalasin D, and microtubule inhibitors, such as Colchicine, Nocodazole, Vinblastine, and Taxol. The results showed that Cytochalasin D reduced about 60–80% of Cronobacter invasion into H4 cells and 50% of E. coli K1 invasion. In contrast, Colchicine reduced the invasion of some strains to just 2% compared to untreated cells. Meanwhile, Nocodazole and Taxol increased the invasion of C. sakazakii 709 and C. malonaticus 1569 into H4 cells by about 140% and 160%, respectively, while slightly inhibiting other strains. In Caco-2 cells, certain strains exhibited increased invasion due to Cytochalasin D, Vinblastine, and Colchicine treatment. This led to increases of up to 500%, 227%, and 248% compared to untreated cells. However, Nocodazole and Taxol decreased invasion into Caco-2 cells, with only E. coli K1 showing an increase of about 150% in Taxol-treated cells. The findings with eukaryotic cytoskeleton inhibitors on neonatal H4 cells suggest that bacterial invasion mainly relies on microfilaments or microfilament-dependent. No specific dependence on the cytoskeleton was seen in Caco-2 cells. In conclusion, cytoskeletal inhibitors significantly affected bacterial invasion, specifically Cronobacter, compared to untreated cells. This suggests that invasion methods may vary by strain and are influenced by how each inhibitor alters cytoskeleton behavior. Therefore, the invasion process, both with and without cytoskeletal inhibitors, is crucial for understanding how bacteria manipulate cell components during infection. Full article

Mastitis, an inflammatory disease caused by the invasion of various pathogenic microorganisms into mammary gland tissue, is a core health issue plaguing the global dairy industry. The consequences of this disease are manifold. In addition to directly compromising the health and welfare of dairy cows, it also precipitates a substantial decline in lactation function, a precipitous drop in raw milk production, and alterations in milk composition (e.g., increased somatic cell counts and imbalanced ratios of milk protein to fat). These changes result in a marked degradation of milk quality and safety, and in turn, engender significant economic losses for the livestock industry. Therefore, the establishment and implementation of a comprehensive prevention and control system is a key strategy to effectively curb the occurrence of mastitis, reduce its incidence rate, and minimise economic losses. This review systematically explores the complex etiological factors and pathogenic mechanisms of mastitis in dairy cows, and summarises various diagnostic methods, including milk apparent indicators monitoring, pathogen detection, physiological parameter monitoring, omics technologies, and emerging technologies. Furthermore, it undertakes an analysis of treatment protocols for mastitis in dairy cows, with a particular emphasis on the significance of rational antibiotic use and alternative therapies. Moreover, it delineates preventive measures encompassing both environmental and hygiene management, and dairy cow health management. The objective of this paper is to provide a comprehensive and scientific theoretical basis and practical guidance for dairy farming practices. This will help to improve the health of dairy cows, ensure a stable supply of high-quality dairy products, and promote the sustainable and healthy development of the dairy farming industry. Full article

An outbreak characterized by clinical signs of diarrhea and paralysis, occasionally progressing to fatal outcomes, occurred at an ostrich breeding facility. Conventional antibiotic treatments proved ineffective. To investigate the etiology of the disease, brain and liver specimens were collected for diagnostic analysis. An Escherichia coli (E. coli) isolate, designated strain HZDC01, was obtained from cerebral tissues, and whole-genome sequencing was performed for genomic characterization. Genomic analysis revealed that the chromosomal DNA harbors numerous resistance genes, conferring multidrug resistance through complex mechanisms. Furthermore, a p0111-type plasmid carrying the bla_CTX-M-55 gene and an IncX1-type plasmid harboring rmtB, sul1, APH(6)-Id, tet(A), AAC(3)-IIc, aadA2, bla_TEM-1B, and floR genes were identified. These plasmids carry numerous mobile genetic elements that can disseminate via horizontal gene transfer, thereby amplifying the risk of resistance-gene spread within bacterial populations. Additionally, the ibeB and ibeC genes, which encode proteins involved in the invasion of brain microvascular endothelial cells, were identified. These genes may facilitate E. coli penetration of the blood–brain barrier, potentially leading to meningitis and posing a life-threatening risk to the host. This is the first report of the isolation and characterization of extended-spectrum beta-lactamase E. coli from the brain of an ostrich with paralysis. The findings provide valuable genomic insights into the antimicrobial resistance profiles and pathogenic mechanisms of ostrich-derived E. coli isolates. Full article