Search Results (7,873)

Acinetobacter baumannii is a critical priority ESKAPE pathogen whose resistome co-occurrence architecture, temporal dynamics, and One Health distribution remain poorly characterized. A total of 20,739 genomes (2000–2025; NCBI, PubMLST, BV-BRC) were annotated using CARD-RGI v6.0.5, AMRFinderPlus v4.2.7, and ResFinder v4.7.2. A co-occurrence network was constructed using Jaccard filtering (≥10%; >0.30) with Bayesian bootstrap and Louvain. Temporal trends were assessed by linear regression with Benjamini–Hochberg (2003–2024), and One Health compartments were assessed using balanced PERMANOVA (Bray–Curtis, 999 permutations). The network comprised 41 nodes and 82 edges with a small-world topology; five communities and nine hub genes were identified. Eighteen ARGs showed significant trends (FDR); six last-resort determinants (blaOXA-23-like, blaNDM, armA, ftsI, msr(E), mph(E)) increased in prevalence. The compartment explained significant variance in the resistome (R² = 0.210; p < 0.001). abaF showed the highest One Health convergence (0.814), and blaNDM was detected in 52 countries. The A. baumannii resistome exhibits a convergent architecture of co-resistance: a small-world network preserved in One Health compartments for more than two decades. The rise in six last-resort determinants signals a population-based transition toward broader profiles, establishing a framework for integrated antimicrobial resistance surveillance. Full article

Background/Objectives: The emergence of methicillin-resistant Staphylococcus aureus (MRSA) highlights the need for new antibacterial agents. Here, we report the identification and evaluation of a novel Gram-positive selective antibacterial: NDM-552. Methods: Antibacterial activity was determined by broth microdilution against a panel of Gram-positive and Gram-negative pathogens. Mechanistic studies included BOCILLIN-FL competition assays, microscale thermophoresis (MST), and antibiotic interaction with oxacillin and moenomycin. Additionally, time–kill analyses, frequency-of-resistance measurements, cytotoxicity assays, plasma stability studies, and a murine wound infection model were performed to characterize NDM-552. Results: NDM-552 exhibits activity against Gram-positive pathogens including S. aureus, Enterococcus faecium, and Staphylococcus epidermidis, with minimum inhibitory concentrations (MICs) of 1–2 µg/mL. NDM-552 displays no activity against Gram-negative bacteria. NDM-552 displays bacteriostatic activity against MRSA and additive interactions with oxacillin and moenomycin. The frequency of resistance in MRSA is low (2.39 × 10⁻⁹). BOCILLIN-FL competition assays and MST binding analysis identify the essential penicillin-binding protein 2 (PBP2) as the potential target of NDM-552. NDM-552 demonstrates acceptable cytotoxicity, favorable plasma stability, and reduces bacterial burden in a murine wound infection model. Conclusions: NDM-552 is a potent Gram-positive selective antibacterial agent that potentially targets PBP2-associated cell wall biosynthesis and exhibits in vivo efficacy against MRSA. Findings establish NDM-552 as a promising scaffold for the development of new antibacterial agents. Full article

Background/Objectives: Bacterial colonization is an under-recognized component of antimicrobial resistance (AMR), particularly among cardiovascular outpatients who frequently interact with healthcare services. While surveillance has traditionally focused on multidrug-resistant (MDR) pathogens causing clinical infection, the ecological characteristics of colonization including multisite carriage, polymicrobial communities, and commensal or low-virulence organisms recovered on antimicrobial-containing media remain poorly defined. This study investigated the burden and ecological patterns of colonization by organisms with reduced antimicrobial susceptibility in cardiovascular outpatients. Methods: In this cross-sectional study, 36 adult cardiovascular outpatients were screened using sputum, nasal, and skin specimens (108 samples) on antimicrobial-supplemented selective media. Isolates were identified by MALDI-TOF mass spectrometry, susceptibility was determined using the VITEK 2 system, and colonization patterns were analyzed using exact statistical methods. Results: Colonization by organisms with reduced antimicrobial susceptibility was detected in 61.1% of patients (95% CI, 44.9–75.2), and at least one validated MDR pathogen in 52.8% (95% CI, 37.0–68.0). Sputum showed the highest colonization prevalence. Multisite colonization occurred in 72.7% of colonized patients, with 40.9% positive at all three anatomical sites. Polymicrobial colonization was common (mean 1.9 species per colonized patient). Resistant commensal bacteria including Neisseria flavescens, Neisseria mucosa, Moraxella catarrhalis, and Lacticaseibacillus casei were recovered alongside recognized pathogens and showed reduced susceptibility across multiple antibiotic classes. Colonization showed significant concordance across anatomical sites, indicating a whole-body colonization state rather than a series of independent site events. Prior hospitalization and concurrent antibiotic therapy were significantly associated with colonization, whereas prior percutaneous coronary intervention and individual comorbidities were not. Conclusions: Cardiovascular outpatients frequently harbour complex bacterial communities characterized by multisite colonization, polymicrobial carriage, commensal and low-virulence organisms recovered on selective media, and MDR pathogens. These findings highlight bacterial colonization as a potential community reservoir of AMR and support targeted pre-procedural screening together with community antimicrobial stewardship. As a single-centre, cross-sectional study of 36 patients, these results are exploratory and hypothesis-generating and require confirmation in larger, multicentre cohorts. Full article

Background: Highly pathogenic avian influenza (HPAI) poses a critical global threat to both the poultry industry and public health. Although Morocco currently maintains HPAI-free status, the country faces substantial risk due to its location along major migratory flyways and its extensive commercial trade networks within the poultry sector. Available data indicate that the links between live bird markets, production farms, and related facilities in the poultry sector constitute a pivotal determinant of disease epidemiology. This study aimed to analyze these movements and determine how they can influence the spread of the disease and to guide policymakers in developing effective risk-based surveillance and control strategies tailored to the local context.: A questionnaire-based cross-sectional survey was conducted across the Casablanca-Settat region, including nine provinces and 138 municipalities, to investigate the movement patterns within the poultry sector in this region. Social network analysis (SNA) was employed to construct a movement network, and findings were spatially visualized using Geographic Information Systems (GIS) and analyzed through network analysis in R.: A total of 945 transport routes were recorded in 126 municipalities. Centrality measures identified three predominant network nodes exhibiting high degree and betweenness centrality values. Our findings indicate that although the network has a low density, the transmission of IAHP remains critical due to frequent bidirectional links and a heterogeneous network structure. The high concentration of movements by a few “hub” municipalities leads to an early emergence and rapid dissemination.: The identification of highly influential nodes allows veterinary authorities to prioritize and target surveillance activities toward municipalities with the greatest likelihood of disease introduction or persistence. The network’s structural connectivity suggests a theoretical potential for rapid HPAI spread, underscoring the importance of the frequent bidirectional links identified between municipalities. This protects both Morocco’s poultry industry and public health. Full article

Acinetobacter (A.) baumannii is an important multidrug-resistant pathogen increasingly recognized across animal and environmental settings, and carbapenem-resistant A. baumannii (CRAB) is classified as a critical-priority pathogen by the World Health Organization. This study investigated the antimicrobial resistance (AMR) and genomic characteristics of 122 A. baumannii isolates comprising 72 veterinary and 50 environmental isolates collected in Andhra Pradesh, India. Antimicrobial susceptibility testing, whole-genome sequencing (WGS), resistance and virulence gene profiling, multilocus sequence typing (MLST), core-genome analysis, single nucleotide polymorphism (SNP) phylogeny, and pan-genome analysis were performed. Overall, 58.2% of isolates were multidrug-resistant (MDR), and 41.8% were extensively drug-resistant (XDR). Sequence type (ST) 52 predominated among veterinary isolates, whereas ST2 was more frequent among environmental isolates. The presence of carbapenem-resistant isolates along with the ST2 lineage enhances the similarity to clinical A. baumannii. Several intrinsic resistance genes, including blaOXA-23, armA, aph(3″)-Ib, aph(6)-Id, tet(B), mph(E), and msr(E), were more prevalent in the ST2-associated population. Virulence-associated determinants were widely conserved. Core-genome MLST (cgMLST) and core-genome SNP (cgSNP) analyses identified highly related isolates within both lineages, while pairwise SNP differences were 0–7. Pan-genome analysis identified 4204 gene clusters and distinct accessory gene patterns between ST2 and ST52. These findings indicate that resistance gene distribution was closely associated with lineage structure and support integrated genomic surveillance of A. baumannii across animal and environmental reservoirs. Full article

Fungal pathogens, such as Fusarium spp. and Alternaria spp., cause substantial yield losses worldwide through root and fruit rot, wilting, and leaf and fruit spots, and increasing restrictions on chemical pesticides have intensified interest in sustainable alternatives such as essential oils, plant extracts, and microbial biocontrol agents. However, these three treatment categories are rarely compared directly under identical experimental conditions, which limits conclusions about their relative efficacy. This study directly compared, for the first time under the same in vitro conditions, the antifungal activity of peppermint and thyme essential oils, clove and rosemary plant extracts, and three commercial biological products (Mycostop, Asir Fruit, Aegis) against Fusarium avenaceum and Alternaria alternata using the agar incorporation method, with fungicidal versus fungistatic activity determined by reinoculation. Most treatments inhibited mycelial growth of both pathogens relative to the untreated control, although a few treatments (Asir Fruit at early DAI and lowest-concentration thyme EO) showed no inhibition or even slight stimulation of A. alternata growth. At 7 days after inoculation, thyme essential oil (1000 µL/L) and clove plant extract at all concentrations tested completely inhibited both pathogens, and reinoculation confirmed that clove extract alone was fungicidal, likely reflecting its high eugenol content and consequent irreversible membrane damage; all other treatments were fungistatic, consistent with reversible effects on membrane permeability. Peppermint essential oil (2000 µL/L) inhibited F. avenaceum and A. alternata by 96% and 73%, respectively, while rosemary extract was comparatively weaker (57% and 21%). Among the commercial products, Mycostop, which contains Streptomyces griseoviridis, was the most effective, plausibly reflecting sustained antagonistic activity beyond metabolite secretion alone. These findings indicate that clove extract and thyme oil match or exceed commercial biocontrol products in vitro and warrant evaluation under greenhouse and field conditions as candidates for integrated disease management. Full article

Candida albicans biofilms are a major cause of persistent infections and contribute to antifungal resistance as well as limitations in drug delivery. Targeting virulence traits such as biofilm formation and hyphal transition represents an effective strategy for controlling fungal pathogenicity without exerting strong selective pressure on planktonic growth. In this study, a library of structurally diverse benzophenone derivatives was screened to identify compounds with antibiofilm and anti-hyphal activities against azole-resistant C. albicans. Most benzophenone derivatives exhibited weak antifungal activity (MIC ≥ 200 µg/mL). However, several halogenated benzophenones markedly suppressed biofilm formation. Among them, decafluorobenzophenone at 10 µg/mL displayed the strongest inhibition, reducing biofilm formation to approximately 1–2% of control levels while maintaining substantial planktonic cell viability. Microscopy confirmed hyphal suppression, while qRT-PCR showed a 36-fold reduction in ALS3 expression. These findings indicate that multi-halogenated benzophenones act primarily as anti-virulence agents targeting biofilm formation and hyphal development. Molecular docking suggested a possible interaction of decafluorobenzophenone with the Als3 binding pocket. Decafluorobenzophenone showed low toxicity, with unaffected Caenorhabditis elegans viability at 10 µg/mL, plant germination at 100 µg/mL, and only slight hemolysis at 100 µg/mL. The results highlight halogen substitution as a key structural determinant and identify benzophenone scaffolds as promising leads for developing novel antibiofilm strategies against azole-resistant Candida infections. Full article

Escherichia coli is a highly diverse bacterial species that includes strains with significant pathogenic potential for both animals and humans. Urban pigeons (Columba livia domestica) are widely distributed and frequently interact with human environments. In contrast, exhibition pigeons are maintained under controlled conditions, providing an opportunity to compare bacterial populations across different ecological settings. Comparative data on virulence-associated gene patterns between free-living urban and exhibition pigeon populations remain limited, particularly when both populations are investigated within the same geographical setting. The present study aimed to investigate the distribution and co-occurrence patterns of selected virulence-associated genes in Escherichia coli isolates recovered from urban and exhibition pigeons. A total of 453 faecal samples (153 urban and 300 exhibition pigeons) were collected, from which 133 Escherichia coli isolates were recovered (65 from urban and 68 from exhibition pigeons), corresponding to an overall isolation rate of 29.4%. A representative subset of isolates was independently confirmed by species-specific PCR and Sanger sequencing before virulence gene profiling. Subsequently, all isolates were screened for six virulence-associated genes (fimC, ompA, tsh, hlyA, astA, and iroN) by PCR. Virulence gene prevalence, gene profiles, co-occurrence patterns, and virulence scores were analysed, and statistical comparisons between groups were performed. The most prevalent gene was ompA (88.0%), followed by fimC (66.2%) and iroN (32.3%), whereas hlyA was detected only sporadically (3.8%). The most common virulence profile was fimC + ompA (24.8%), followed by ompA alone (20.3%). Co-occurrence analysis identified fimC and ompA as the most frequently co-detected gene pair (79/133 isolates; 59.4%); however, their association was weak and not statistically significant (φ = 0.078, p = 0.371). Frequent co-detection with the iron acquisition-associated gene iroN was also observed. No statistically significant differences were observed in the distribution of the investigated virulence-associated genes between urban and exhibition pigeon isolates, although urban isolates exhibited a broader diversity of gene combinations. In conclusion, pigeon-derived E. coli isolates harboured diverse combinations of selected virulence-associated genes, with adhesion-associated genes being the most frequently detected determinants. These findings provide baseline data on the distribution of selected virulence-associated genes in pigeon-derived Escherichia coli isolates and support future studies incorporating additional virulence markers, whole-genome sequencing, and comparative analyses to understand their epidemiological relevance better. Full article

Senecavirus A (SVA), an emerging causative agent of porcine vesicular disease, belongs to the genus Senecavirus of the family Picornaviridae. The virus has been circulating in pig herds in the USA dating back to 1988, evolved into clinically significant pathogenic SVA variants causing a pandemic in the USA and Canada since 2014, and thereafter gradually spread to the Americas and Asia. To date, most studies have illustrated the infection dynamics, epidemiology, diagnostic methods, and vaccine development, yet the molecular pathogenesis of SVA remains incompletely characterized. As a novel picornavirus capable of establishing persistent subclinical infections, SVA has been detected in tissues such as tonsils and testicles for up to 156 days post-infection, posing a substantial challenge to swine health and production systems. In parallel, SVA has gained attention as an oncolytic virotherapy candidate for neuroendocrine tumors due to its tumor-selective tropism. Therefore, elucidating the mechanisms underlying SVA pathogenesis will not only support the development of effective countermeasures for swine but also inform the engineering of recombinant variants with enhanced therapeutic potential for human oncology. This review comprehensively summarizes the current knowledge on viral and host determinants of SVA pathogenesis, from the viral genome, evolution, and recombination to ANTXR1 host immunity, and programmed cell death, and presents future research directions, aiming to identify key knowledge gaps to guide future studies on SVA. Full article

Endophytes are diverse microorganisms inhabiting plant tissues that can promote plant growth, enhance stress tolerance, or suppress pathogens. However, the ecological roles of endophytes after host senescence and death remain poorly understood. This review examines how a subset of endophytes helps maintain ecosystem function in living plants, senescent tissues, litter, and associated microbial environments. Mechanisms of endophyte-mediated plant protection in living plants include pathogen inhibition, host regulation, nutrient acquisition, and abiotic stress tolerance. We also investigate post-senescence persistence and potential roles in litter decomposition and nutrient cycling via microbial and functional legacies, priority effects, extracellular enzyme activities, and community reassembly. Vertical transmission and horizontal dispersal can move microorganisms among stages, whereas host filtering acts after arrival to determine which microorganisms establish within host tissues. However, a full same-strain life-history loop has not been established. We propose an open, non-linear ecological continuum for selected endophytes that connects endophytic colonisation, saprotrophic persistence, and potential new-host establishment. In the future, longitudinal, strain-resolved, multi-omics, and synthetic-community studies will be conducted to verify the cross-stage connections and offer a microbial framework for plant protection, litter management, and ecological restoration. Full article

Ticks are prominent hosts for many viruses that are pathogenic to humans on almost every continent. Despite the documented historical association of ticks with viral disease in humans, clinical case reports are low, likely due to under-recognition of these pathogens. A key feature of understanding tick-borne virus transmission to humans lies in the natural invertebrate and vertebrate hosts supporting ecological maintenance. As humans are often infected as incidental hosts during the tick–virus life cycle, determining relevant ticks and mammals involved in maintenance can inform prevention strategies, surveillance priorities, and diagnostic assay development. This review aims to cover common trends in tick-borne virus ecology, including the wide breadth of implicated tick species, an unclear role for definitive vertebrate reservoirs, and the focal distributions of these viruses closely linked to these host ecological features. Here we also provide examples of prominent tick-borne viruses causing human disease between the Old (Africa, Asia, Europe) and New (Americas) Worlds, highlighting parallels in initial discoveries, vectors, and vertebrates including tick-borne encephalitis, Crimean–Congo hemorrhagic fever, severe fever with thrombocytopenia syndrome, Colorado Tick fever, and Powassan, Heartland, and Bourbon viruses. Full article

The peptidoglycan (PG) sacculus of Gram-negative bacteria is continuously reorganized by a diverse enzymatic repertoire, including lytic transglycosylases, endopeptidases, carboxypeptidases, amidases and LD-transpeptidases, that operate alongside PG synthases to maintain envelope integrity throughout the cell cycle. This remodeling machinery has been extensively characterized in the context of growth and division and it is now emerging also as a key determinant of bacterial survival under non-growing and stress conditions. This review summarizes current knowledge on PG remodeling in Gram-negative bacteria, with emphasis on its regulation during stationary phase, environmental stress, and outer membrane perturbation. How these remodeling pathways, characterized by increased 3–3 cross-linking and enhanced PG–outer membrane coupling, contribute to survival under β-lactam exposure and how related enzymatic configurations can give rise to antibiotic tolerance and resistance is also discussed. Finally, recent progress in targeting PG remodeling enzymes, particularly lytic transglycosylases and peptidases, as adjuvant strategies to potentiate existing antibiotics are reviewed. In summary, PG remodeling represents a mechanistically validated but still underexploited target for addressing antibiotic tolerance and resistance in Gram-negative pathogens. Full article

Background/Objectives: The apelin/APJ system has demonstrated neuroprotective effects in experimental studies by regulating key pathogenic mechanisms of ischemic stroke, including oxidative stress, apoptosis, cerebral edema, and inflammation. This study aimed to investigate the role of serum apelin levels measured within the first 24 h in predicting 28-day and long-term mortality in patients with ischemic cerebrovascular disease. Methods: This prospective cohort study included 44 patients hospitalized with a diagnosis of acute ischemic stroke due to large artery atherosclerosis. Serum apelin levels were measured using the ELISA method from blood samples obtained within the first 24 h after symptom onset. Patients were prospectively followed for 28-day and long-term mortality. Results: During the follow-up period, 32.6% of the patients died. The median serum apelin level was significantly higher in the deceased group compared to the survivors [105.0 pg/mL vs. 55.8 pg/mL]. In ROC analysis, the area under the curve (AUC) for apelin in predicting mortality was 0.727 (95% CI: 0.550–0.903). The optimal cut-off value was determined as ≥70.47 pg/mL (sensitivity: 85.71%, specificity: 62.07%). In Kaplan–Meier analysis, the 28-day mortality rate was 52.2% in the high-apelin group (≥70.47 pg/mL), whereas it was 10.0% in the low-apelin group (<70.47 pg/mL) (p = 0.004). In multivariate Cox regression analysis, an apelin level <70.47 pg/mL was identified as an independent prognostic factor (HR: 0.16; 95% CI: 0.03–0.94). The cumulative survival rates at days 28, 56, and 180 were 56.1%, 46.7%, and 11.7%, respectively, in the high-apelin group, while these rates were 100%, 100%, and 81.8%, respectively, in the low-apelin group. The mean NIHSS score was significantly higher in the high-apelin group, and a strong, positive, and highly significant correlation was found between serum apelin level and NIHSS score (r = 0.703, p < 0.001). Conclusions: High serum apelin levels measured within the first 24 h in acute ischemic stroke are associated with increased 28-day and long-term mortality. The association of high endogenous apelin levels with poor prognosis in the clinical setting suggests that apelin is mobilized as a stress response during ischemia, and that elevated circulating levels may actually reflect the severity of the ischemic insult. Full article

Background/Objectives: Mitochondrial Complex V (Complex V [CX-V], or ATP synthase) is the terminal enzyme of oxidative phosphorylation and is responsible for the majority of cellular ATP production. An increasing body of evidence suggests that CX-V dysfunction may contribute to mitochondrial impairment observed in neurodegenerative disease. This review evaluated current research on the structure, regulation, and function of CX-V, examined the consequences of CX-V dysfunction, and assessed its proposed role in neurodegenerative disorders. Methods: A comprehensive review of the published literature was carried out, with emphasis on primary research investigating CX-V structure and function, inherited CX-V disorders, and experimental evidence linking CX-V dysfunction to neurodegenerative disease. The reviewed studies used a range of experimental approaches, including structural biology, biochemical studies, patient-derived cellular models, animal models and post-mortem human tissue. Results: Current evidence demonstrates that disruption of CX-V impairs ATP production, alters mitochondrial membrane potential, and oxidative phosphorylation, and that pathogenic variants cause primary mitochondrial disease. Across Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis/frontotemporal dementia, glaucoma and inherited optic neuropathies, alterations in CX-V activity, regulation and structural integrity are consistently associated with mitochondrial dysfunction. Direct evidence supporting CX-V as a primary driver of neurodegeneration remains very limited, with many observations originating from broader studies of general mitochondrial dysfunction. Conclusions: CX-V dysfunction represents a recurring feature of mitochondrial impairment across a variety of neurodegenerative disorders and may exacerbate neuronal vulnerability by disrupting cellular bioenergetics. Current evidence indicates that CX-V may serve as a common downstream target of multiple pathological pathways rather than acting as a primary pathological factor. Future studies require direct assessment of CX-V activity in clinically relevant human models and patient tissues to determine its contribution to disease progression and examine its potential as a therapeutic target. Full article

Stenotrophomonas maltophilia is increasingly recognized as a difficult-to-treat healthcare-associated opportunistic pathogen, particularly in critically ill and immunocompromised patients, in whom it causes severe respiratory, bloodstream, and device-associated infections. Its intrinsic resistance to multiple antimicrobial classes, capacity to acquire additional resistance determinants, and ability to establish persistent biofilms substantially limit therapeutic options. This review integrates current knowledge of the structural basis, regulatory circuitry, and ecological interactions governing S. maltophilia biofilm development and examines how these processes converge with antimicrobial resistance. Biofilm formation is driven by coordinated adhesion and motility, extracellular matrix production, quorum sensing, cyclic di-GMP signaling, two-component regulatory systems, and adaptive responses to iron limitation and oxidative stress. Multidrug efflux systems contribute not only to antibiotic extrusion but also to membrane homeostasis, motility, stress adaptation, and biofilm-associated phenotypes, thereby providing a functional link between antimicrobial resistance and bacterial persistence. In polymicrobial communities, interspecies signaling and competitive or cooperative interactions further reshape biofilm architecture and antimicrobial tolerance. Collectively, current evidence indicates that S. maltophilia biofilm formation arises from interconnected regulatory networks rather than isolated molecular determinants. Targeting matrix assembly, signaling pathways, stress adaptation, or resistance-associated physiology may therefore complement conventional antimicrobial therapy. Future studies should prioritize clinically representative isolates, physiologically relevant multispecies models, and in vivo validation to translate mechanistic insights into effective anti-biofilm interventions. Full article