Search Results (7,771)

In plants, resistance genes (R) are key players in combatting diseases caused by various phytopathogens. Typically, resistance relies on detecting a single pathogen-derived molecular pattern. However, R-gene-mediated resistance is often race specific, follows the gene-for-gene hypothesis, and can be overcome in field conditions as pathogens evolve. On the contrary, altering plant susceptibility genes (S-genes) facilitates compatibility and results in broad and durable resistance. S-genes are negative regulators present in plants and exploited by pathogens to facilitate their growth and cause infection. Several studies across crop species have reported manipulation of S-genes using genome editing to confer broad spectrum resistance. This review focuses on the plant defense mechanism against biotic stress, R-genes vs. S-genes, different types/classes of S-genes, different tools for S-gene discovery, and the use of gene editing technologies to target S-genes in addition to their applications, challenges, and future perspectives. Full article

Gray mold, caused by Botrytis cinerea Pers. Fr. (teleomorph: Botryotinia fuckeliana), is a major disease affecting Moroccan vineyards. However, limited information is available on the natural populations of this pathogen. In this study, 82 single-spore isolates collected from vineyards in two major wine-growing regions were evaluated for phenotypic, physiological, and molecular variability. The isolates exhibited differences in morphotypes, conidial size, and sclerotia production on PDA medium. Temperature significantly affected mycelial growth rate (mm d⁻¹). All isolates were virulent on grapevine leaves, showing varying levels of aggressiveness. Among the representative isolates, 20 were heterothallic and 2 were homothallic. Mating-type analysis revealed that 12% belonged to MAT1-1 and 75% to MAT1-2. Transposable element genotyping showed that the population was composed of 41.7% transposa, 29.2% vacuma, 16.7% Flipper-only, and 12.5% Boty-only. This work represents the first report on genotypic variation in B. cinerea populations from Moroccan vineyards. The findings provide new insights into the morphenotypic and genetic diversity of the pathogen and may support the development of improved strategies for disease management. Full article

Conventional plant disease management primarily depends on chemical pesticides. However, with the rising concerns related to human health, environmental sustainability, and the emergence of resistant pathogens, biocontrol agents (BCAs) have gained more attention as eco-friendly alternatives. Among the potential biocontrol agents, yeasts stand out due to their safety, adaptability, and diverse antagonistic mechanisms, ranging from competition and enzyme secretion to volatile compound production and immunity induction. Despite their potential, yeast-based BCAs face limitations in field efficacy, regulation, and an incomplete understanding of their molecular interactions. Most current studies focus on simple, pairwise interactions, overlooking the complexity of agroecosystems, where plants, pathogens, and BCAs interact within broader microbial communities. This review addresses the importance of understanding tripartite interactions among plants, pathogens, and yeasts, supported by integrated transcriptomic and comparative genomic approaches, as well as meticulous observations of phenotypic expressions to uncover strain-specific defense mechanisms and mode of action. By referring to well-studied models like Blumeria graminis f.sp. hordei–Hordeum vulgare–Pseudozyma flocculosa and Trichoderma tripartite systems, we highlight the underexplored potential of yeasts to modulate plant immunity and influence pathogen behavior through complex molecular crosstalk. Bridging these knowledge gaps through integrating proteomic, metabolomic, and transcriptomic analyses, we can better harness yeasts in sustainable and targeted biocontrol strategies. Full article

Antibiotic resistance remains one of the most formidable challenges to modern medicine, threatening to outpace therapeutic innovation and undermine decades of clinical progress. While resistance was once viewed narrowly as a clinical phenomenon, it is now understood as the outcome of complex ecological and molecular interactions that span soil, water, agriculture, animals, and humans. Environmental reservoirs act as silent incubators of resistance genes, with horizontal gene transfer and stress-induced mutagenesis fueling their evolution and dissemination. At the molecular level, advances in genomics, structural biology, and systems microbiology have revealed intricate networks involving plasmid-mediated resistance, efflux pump regulation, integron dynamics, and CRISPR-Cas interactions, providing new insights into the adaptability of pathogens. Simultaneously, the environmental dimensions of resistance, from wastewater treatment plants and aquaculture to airborne dissemination, highlight the urgency of adopting a One Health framework. Yet, alongside this growing threat, novel therapeutic avenues are emerging. Innovative β-lactamase inhibitors, bacteriophage-based therapies, engineered lysins, antimicrobial peptides, and CRISPR-driven antimicrobials are redefining what constitutes an “antibiotic” in the twenty-first century. Furthermore, artificial intelligence and machine learning now accelerate drug discovery and resistance prediction, raising the possibility of precision-guided antimicrobial stewardship. This review synthesizes molecular insights, environmental drivers, and therapeutic innovations to present a comprehensive landscape of antibiotic resistance. By bridging ecological microbiology, molecular biology, and translational medicine, it outlines a roadmap for surveillance, prevention, and drug development while emphasizing the need for integrative policies to safeguard global health. Full article

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen frequently associated with delayed wound healing, particularly in chronic skin injuries. Its capability to form biofilms, secrete virulence factors, and the faculty to compete with other microorganisms makes it a major challenge in clinical wound management. Recent literature reveals different molecular and cellular mechanisms through which P. aeruginosa disrupts the wound healing process. Findings highlight that it interferes with key phases of healing by modulating host immune responses, degrading extracellular matrix components, and inhibiting keratinocyte migration. Its quorum-sensing systems regulate the expression of critical virulence factors such as exotoxin A, elastases, pyocyanin, and rhamnolipids. Additionally, the production of the biofilm matrix components alginate, and polysaccharides provide protection against host defenses and antibiotics. Interactions with other microorganisms, including antagonistic effects on Staphylococcus epidermidis and synergistic relationships with Staphylococcus aureus, modify the wound microbiota. Promising therapeutic alternatives have shown efficacy in disrupting biofilms and reducing virulence. These insights remark the importance of targeting both P. aeruginosa and its ecological interactions to enhance wound healing outcomes and develop more effective treatments. This review aimed to highlight the pathogenic role of P. aeruginosa and its interactions with other microbial species in the context of skin wound healing. Full article

Aquaculture has rapidly become a vital sector for ensuring global food security by meeting the growing demand for animal protein. Bangladesh, one of the world’s leading aquaculture producers, recorded a production of 4.91 million MT in 2022–2023, largely driven by inland farming systems. Despite this remarkable growth, the sector is highly vulnerable to disease outbreaks, which are aggravated by different factors. Pathogens such as bacteria, viruses, fungi, and parasites cause significant losses, while conventional disease diagnosis in Bangladesh still depends mainly on visual assessment and basic laboratory techniques, limiting early detection. This narrative review highlights recent advances in diagnostics as molecular tools, immunodiagnostics, nanodiagnostics, machine learning, and next-generation sequencing (NGS) that are widely applied globally but remain limited in Bangladesh due to infrastructure gaps, lack of skilled manpower, and resource constraints. Current treatment strategies largely rely on antibiotics and aquaculture medicinal products (AMPs), often misused without proper diagnosis, contributing to antimicrobial resistance (AMR). Promising alternatives, including probiotics, immunostimulants, vaccines, and enhanced biosecurity, require greater adoption and farmer awareness. The near-term priorities for Bangladesh include standardized disease and AMR surveillance, prudent antibiotic stewardship, phased adoption of validated rapid diagnostics, and investment in diagnostic and human capacity. Policy-level actions, including a national aquatic animal health strategy, stricter antimicrobial regulation, strengthening diagnostic infrastructure in institution, are crucial to achieve sustainable disease management and ensure long-term resilience of aquaculture in Bangladesh. Full article

The Mycobacterium tuberculosis complex (MTBC) represents one of the most significant bacterial pathogen groups affecting both animals and humans worldwide. This review provides a comprehensive analysis of MTBC species distribution across different animal hosts and evaluates current laboratory diagnostic methodologies for pathogen detection and identification. The complex comprises seven primary species: Mycobacterium bovis, M. caprae, M. tuberculosis, M. microti, M. canettii, M. africanum, and M. pinnipedii, each exhibiting distinct host preferences, geographical distributions, and pathogenic characteristics. Despite sharing >99% genetic homology, these species demonstrate variable biochemical properties, morphological features, and pathogenicity profiles across mammalian species. Current diagnostic approaches encompass both traditional culture-based methods and advanced molecular techniques, including whole genome sequencing. This review emphasises the critical importance of rapid, accurate detection methods for effective tuberculosis surveillance and control programmes in veterinary and public health contexts. Full article

Background: Rare pediatric neurological diseases (RPND) often remain undiagnosed for years, creating prolonged and costly diagnostic odysseys. Combining Human Phenotype Ontology (HPO)-based deep phenotyping with exome sequencing (ES) and reverse phenotyping offers the potential to improve diagnostic yield, accelerate diagnosis, and support sustainable healthcare in resource-limited settings. Objectives: To evaluate the diagnostic yield and clinical impact of an integrated approach combining deep phenotyping, ES, and reverse phenotyping in children with suspected RPNDs. Methods: In this multicenter observational study, eighty-one children from eleven hospitals in South Kazakhstan were recruited via the Central Asian and Transcaucasian Rare Pediatric Neurological Diseases Consortium. All patients underwent standardized HPO-based phenotyping and ES, with variant interpretation following ACMG guidelines. Reverse phenotyping and interdisciplinary discussions were used to refine clinical interpretation. Results: A molecular diagnosis was established in 34 of 81 patients (42%) based on pathogenic or likely pathogenic variants. Variants of uncertain significance (VUS) were identified in an additional 9 patients (11%), but were reported separately and not included in the diagnostic yield. Reverse phenotyping clarified or expanded clinical features in one-third of genetically diagnosed cases and provided supportive evidence in most VUS cases, although their classification remained unchanged. Conclusions: Integrating deep phenotyping, ES, and reverse phenotyping substantially improved diagnostic outcomes and shortened the diagnostic odyssey. This model reduces unnecessary procedures, minimizes delays, and provides a scalable framework for advancing equitable access to genomic diagnostics in resource-constrained healthcare systems. Full article

Cardiomyopathies affect over 3 million individuals globally, with conventional treatments exhibiting up to 60% resistance and 25% 30-day readmission rates. This review synthesizes the current evidence on the role of neuro-immune interactions in the pathogenesis of cardiomyopathy and evaluates emerging therapies targeting this axis. We systematically examined clinical trials and mechanistic and multi-omics data across cardiomyopathy phenotypes, focusing on autonomic-immune dysregulation. Sympathetic overactivation, present in approximately 85% of patients, correlates with elevated pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and contributes significantly to therapeutic non-response. Concurrent parasympathetic withdrawal impairs cholinergic anti-inflammatory pathways, as reflected by reduced heart rate variability and baroreflex sensitivity. At the molecular level, shared mechanisms include inflammasome activation, neuroimmune synaptic signaling, and neurogenic inflammation. Emerging therapies targeting this axis are promising. Vagus nerve stimulation, as demonstrated in the INOVATE-HF trial, improves functional outcomes, whereas IL-1β antagonists reduce cardiovascular events by 15–20% in the context of inflammatory diseases. Bioelectronic interventions, such as transcutaneous vagal nerve stimulation and baroreflex activation therapy, offer noninvasive dual-modulatory strategies that address both neural and immune pathways, positioning the neuroimmune axis as a central driver of cardiomyopathy, regardless of etiology. The integration of genetic and metabolomic profiling may enable precision therapies targeting neuroimmune circuits, thereby overcoming the limitations of hemodynamic-focused care. This mechanistic framework shifts the therapeutic paradigm from symptomatic relief to targeted modulation of pathogenic pathways, with implications for millions of patients with cardiomyopathy and broader inflammatory cardiovascular disorders. Full article

Background/Objectives: Malaria remains the most critical parasitic disease globally, responsible for over 600.000 deaths annually. In sub-Saharan Africa, co-infections of Plasmodium falciparum with other pathogens, particularly Staphylococcus aureus, are common in children with severe malaria. Therefore, the design of new compounds targeting both pathogens appears to be an urgent priority. Methods: A small series of hybrid compounds was designed and synthesized by linking the pharmacophore of the antimalarial drug chloroquine with the phenothiazine core. These compounds were tested in vitro against a panel of microbial strains and further analyzed through in silico simulations to predict their physical-chemical properties. Results: Compounds 4b and 5b emerged the most potent candidates of the series, showing a sub-micromolar inhibitory activity on P. falciparum, and a promising micromolar potency on S. aureus alongside with a low toxicity on mammalian cells. Molecular docking followed by molecular dynamics (MD) simulations identified the respiratory membrane NDH-2 enzyme as common target in both pathogens. Conclusions: Both experimental and computational findings provide compelling evidence for the use of the designed compounds in a STOP strategy, i.e., Same-Target-Other-Pathogen, to treat malaria and bacterial infections concurrently. Full article

Ilex verticillata (winterberry) is a valuable ornamental shrub increasingly threatened by leaf blight, a disease that compromises its aesthetic and economic value. While fungal pathogens like Alternaria alternata are known to cause leaf blight in horticultural crops, their role in I. verticillata and the host’s defense mechanisms have not been fully characterized. Our study investigated the pathogen-host interaction by identifying the causal agent and examining the physiological and molecular defense mechanisms of I. verticillata. Through morphological and multi-locus molecular analyses (ITS, TEF1-α, G3PDH, RPB2), A. alternata was confirmed as the primary pathogen, fulfilling Koch’s postulates. Pathogenicity assays revealed distinct disease progression stages, from necrotic lesions to tissue degradation. Transcriptomic profiling uncovered dynamic host responses, with early upregulation of pattern recognition receptors (PRRs) and transcripts encoding antioxidant enzymes (SOD, CAT), followed by downregulation of metabolic pathway genes. Phytohormone analysis highlighted intricate crosstalk, with salicylic acid (SA) peaking during mid-infection and jasmonic acid (JA) rebounding later, reflecting a coordinated defense strategy. Additionally, the oxidative stress marker malondialdehyde (MDA), an indicator of membrane lipid peroxidation, surged early, indicating membrane damage, while sustained induction of antioxidant enzymes suggested adaptive responses. The key finding was distinct phytohormone crosstalk, characterized by a mid-infection SA peak followed by a late JA rebound, alongside an early oxidative burst marked by MDA accumulation and sustained antioxidant enzyme activity. These findings provide a framework for understanding I. verticillata’s defense mechanisms and offer insights for developing targeted disease management strategies, such as resistant cultivar breeding or hormone-mediated interventions. Full article

Healthcare-associated infections (HAIs) in the elderly represent a growing clinical and public health concern, primarily driven by age-related biological remodeling. Key mechanisms include immunosenescence, inflammaging, gut microbiota dysbiosis, and profound metabolic and epigenetic alterations, all of which progressively weaken host defense and resilience to pathogens. In this review, we delineate the molecular pathways underlying these processes, with particular attention to impaired innate and adaptive immune responses, dysfunctional cellular signaling, and disrupted immunometabolic networks that increase susceptibility to multidrug-resistant organisms and aggravate clinical outcomes in older patients. We also address the synergistic impact of frailty-related factors such as malnutrition, multimorbidity, and polypharmacy on infection risk. Finally, we discuss emerging translational perspectives, including nutritional interventions and microbiota-targeted strategies aimed at restoring immune competence and reducing infection burden. By integrating molecular mechanisms with clinical implications, this review highlights innovative opportunities for personalized prevention and management of HAIs in the aging population. Full article

Staphylococcus aureus is a major pathogen responsible for staphylococcal food poisoning (SFP), with its pathogenicity primarily dependent on staphylococcal enterotoxins (SEs). Among these, staphylococcal enterotoxin A (SEA) is a critical risk factor due to its high toxicity, high detection rate (accounting for 80% of SFP cases), strong thermal stability, and resistance to hydrolysis. Traditional SEA immunoassays, such as enzyme-linked immunosorbent assay (ELISA), are prone to false-positive results caused by nonspecific binding interference from S. aureus surface protein A (SpA). In recent years, nanobodies (single-domain heavy-chain antibodies) have emerged as an ideal alternative to address SpA interference owing to their small molecular weight (15 kDa), high affinity, robust stability, and lack of Fc regions. In this study, based on a previously developed highly specific monoclonal antibody against SEA (mAb-4C6), four anti-SEA nanobodies paired with mAb-4C6 were obtained through two-part (four-round) of biopanning from a naive nanobody phage display library. Among these, SEA-4-20 and SEA-4-31 were selected as optimal candidates and paired with mAb-4C6 to construct double-antibody sandwich ELISAs. The detection limits for SEA were 0.135 ng/mL and 0.137 ng/mL, respectively, with effective elimination of SpA interference. This approach provides a reliable tool for rapid and accurate detection of SEA in food, clinical, and environmental samples. Full article

Agrocybe chaxingu is a commercially important edible mushroom in China, valued for its rich bioactive compounds and distinctive umami flavor. In recent years, frequent disease outbreaks have severely limited production, as many pathogens spread rapidly and are difficult to control, posing a significant threat to the sustainable development of the industry. In this study, a systematic disease survey across major A. chaxingu cultivation areas in Jiangxi Province led to the isolation and identification of 17 potential fungal pathogens and 2 potential myxomycete pathogens using combined morphological characterization and multilocus phylogenetic analyses including the internal transcribed spacer (ITS) region, 28S large subunit ribosomal RNA (LSU), translation elongation factor (tef1), RNA polymerase largest subunit (rpb1), RNA polymerase second largest subunit (rpb2), Histone (H3), Beta tubulin (tub2), and 18S ribosomal RNA (18S rRNA). Among the identified diseases, white slime disease showed the highest incidence (17.3%) and was attributed to the slime mold Fuligo gyrosa, with pathogenicity confirmed according to Koch’s postulates. F. gyrosa proved highly virulent to both fruiting bodies and mycelia, enveloping host mycelium via plasmodial expansion, inhibiting growth, inducing structural rupture, and causing progressive degradation. Infection was accompanied by the deposition of characteristic stress-related pigments in the mycelium. This study provides the first detailed characterization of F. gyrosa infection dynamics in A. chaxingu mycelium. These findings provide new insights into the myxomycete pathogenesis in edible fungi and provide a foundation for the accurate diagnosis, targeted prevention, and sustainable management of diseases in A. chaxingu cultivation. Full article

Human cytomegalovirus (HCMV) establishes lifelong latency following primary infection, residing within myeloid progenitor cells and monocytes. To achieve this, the virus employs multiple immune evasion strategies. It suppresses innate immune signaling by inhibiting Toll-like receptor and cGAS-STING pathways. In addition, the virus suppresses major histocompatibility complex (MHC)-dependent antigen presentation to evade T cell recognition. As the downregulation of MHC molecules may trigger NK cell activation, the virus compensates for this by expressing proteins such as UL40 and IL-10, which engage inhibitory NK cell receptors and block activating signals, thereby suppressing NK cell immune surveillance. Viral proteins like UL36 and UL37 block host cell apoptosis and necroptosis, allowing HCMV to persist undetected and avoid clearance. In settings of profound immunosuppression, such as after allogeneic hematopoietic stem cell transplantation (allo-HSCT) or solid organ transplantation, slow immune reconstitution creates a window for viral reactivation. Likewise, immunosenescence and chronic low-grade inflammation during aging increases the risk of reactivation. Once reactivated, HCMV triggers programmed cell death, releasing viral PAMPs (pathogen-associated molecular patterns) and host-derived DAMPs (damage-associated molecular patterns). This release fuels a potent inflammatory response, promoting further viral reactivation and exacerbating tissue damage, creating a vicious cycle. This cycle of inflammation and reactivation contributes to both transplant-related complications and the decline of antiviral immunity in the elderly. Therefore, understanding the immune regulatory mechanisms that govern the switch from latency to reactivation is critical, especially within the unique immune landscapes of transplantation and aging. Elucidating these pathways is essential for developing strategies to prevent and treat HCMV-related disease in these high-risk populations. Full article