Search Results (18,588)

Infective endocarditis (IE) continues to represent a major challenge for global health systems. In 2019, its annual incidence was estimated at 13.8 cases per 100,000 individuals, contributing to approximately 66,300 deaths worldwide. Due to its high morbidity and mortality rates, enhancing preventive measures has become a priority in both clinical practice and ongoing research efforts. Since the publication of the 2015 ESC Guidelines for the management of IE, several pivotal studies have emerged, prompting a re-evaluation and potential update of the existing recommendations. One growing concern is the increasing antibiotic resistance among oral streptococci, particularly to macrolides such as azithromycin and clarithromycin, which now show higher resistance levels than penicillin. Changes in national antibiotic stewardship programs may have inadvertently contributed to a rise in IE incidence, in part due to altered prophylactic practices. At the same time, advances in diagnostic modalities—including more widespread and targeted use of echocardiography in patients with positive blood cultures for organisms like Enterococcus faecalis, Staphylococcus aureus, and various streptococci—have likely improved detection rates. Additionally, innovations in imaging, particularly computed tomography (CT) and nuclear medicine techniques, have enhanced the diagnosis of IE, especially among patients with prosthetic heart valves or implantable cardiac devices. This has allowed for better characterization of patient populations, aiding in the refinement of diagnostic criteria and therapeutic approaches. Furthermore, updated antibiotic treatment protocols, informed by EUCAST’s antimicrobial susceptibility data, have helped tailor antimicrobial regimens to current resistance trends. The combination of improved diagnostic sensitivity and evolving microbial resistance patterns has also led to an increased number of patients being considered for cardiac surgery as part of their treatment pathway. This review seeks to synthesize the latest findings and guideline revisions, offering an integrated overview of recent progress in the diagnosis, medical treatment, and surgical management of infective endocarditis. It will also explore current therapeutic strategies and operative indications in light of the most recent evidence. Full article

Among the many concerns surrounding global health, antimicrobial resistance (AMR) is widely recognized as a major threat, especially critical within livestock production, where restrictions on antibiotic use demand effective preventive alternatives. The documented health benefits and structural stability have positioned yeast-derived postbiotics as an attractive alternative, but research has largely focused on Saccharomyces cerevisiae, leaving non-Saccharomyces yeast species underexplored. To this end, in this study nine non-conventional yeast strains were selected and subjected to different thermal and chemical inactivation methods to determine the most suitable conditions for postbiotic obtention. Based on their physicochemical characterization and scalability potential, heat-treated postbiotics were selected for subsequent in vitro evaluation. Immunomodulatory assays demonstrated that heat-inactivated postbiotics from the different yeast strains were internalized by macrophages and induced dose-and-species-dependent expression of maturation markers CD40 and CD86, as well as TNF-α production, eliciting a proinflammatory response in vitro. Moreover, among all the species evaluated in this work, Rhodotorula mucilaginosa and Wickerhamomyces anomalus stood out for their ability to significantly reduce the adhesion of the enteropathogen enterotoxigenic Escherichia coli (ETEC) to intestinal cells in vitro. These results highlight the species-dependent immunomodulatory and anti-infective properties of selected yeast-derived postbiotics. Full article

Fusariumoxysporum f. sp. cubense race 4 (Foc 4) causes Fusarium wilt by penetrating root cell walls, yet the molecular basis of cell wall-mediated resistance remains poorly understood. Here, we investigated the transcriptional, enzymatic, and cellular responses of the resistant banana cultivar Dongjiao No. 1 (DJ) and its susceptible mutant ke2 following Foc 4 infection. RNA sequencing revealed that DJ specifically upregulated a pectin degradation cassette comprising pectin methylesterase (PME3-Like), pectin acetylesterase (PAE1), and polygalacturonases (PG1, PG3, PG5, PG-Like-4) at the bud seedling stage. Immunolocalization further revealed robust, tissue-specific PME deployment, with stable abundance at the primary infection site and differential redistribution in aerial tissues. This enzymatic cascade degraded homogalacturonan, confirmed by the simultaneous loss of pectin epitopes recognized by JIM5 and JIM7 antibodies. Additionally, the upregulation of PTI1, MAPK cascades, calcium-dependent protein kinases (CDPK3, CML31), and respiratory burst oxidase homologs (RBOHs) was also observed in DJ. The differential transcription of salicylic acid signaling (TGA1–PR1), jasmonic acid derepression (TIFY/JAZ), and flavonoid phytoalexin biosynthesis in DJ further reinforced the defense response. In contrast, ke2 failed to activate the pectin degradation machinery, exhibited attenuated immune signaling, and retained intact pectin vulnerable to pathogen exploitation. These findings establish pectin degradation-mediated immunity as a resistance mechanism in banana and provide potential targets for Fusarium wilt resistance breeding. Full article

Background: Global antibiotic consumption continues to rise across pediatric and adult populations, while the genotoxic consequences of host eukaryotic exposure remain less systematically characterized than the parallel problem of antimicrobial resistance. Several lines of evidence, from molecular cytogenetics, redox biology, and systems toxicology, now permit a more mechanistically resolved synthesis of antibiotic-induced genome stress than was previously possible, although a substantial fraction of this evidence is preclinical and warrants cautious clinical extrapolation. Scope: This narrative review evaluates the molecular mechanisms, cytogenetic biomarkers, and translational implications of antibiotic-induced genotoxicity, with a primary focus on six clinically prominent classes (fluoroquinolones, nitroimidazoles, aminoglycosides, macrolides, β-lactams, and tetracyclines) and a brief extension to glycopeptides and glycylcyclines. We organize the evidence around three convergent mechanistic axes rather than around individual drugs. Key findings: Accumulating evidence supports three intersecting off-target axes: (i) eukaryotic topoisomerase II interference, principally documented for fluoroquinolones; (ii) mitochondrial dysfunction, reflecting the evolutionary kinship between the mitoribosome and bacterial ribosomes; and (iii) inflammation-coupled redox stress, often amplified by microbiome perturbation. These pathways converge on a common spectrum of DNA lesions—including double-strand breaks, oxidatively modified bases, replication-fork stalling, and chromosomal mis-segregation) detected by complementary assays (CBMN-Cyt, comet, γH2AX, and oxidative and mitochondrial biomarkers). Pediatric, pregnant, geriatric, and oncology populations may represent biologically distinct susceptibility strata, although direct human evidence for several of these inferences remains limited. Limitations: Causal inference is constrained by infection as a confounder, frequent use of supratherapeutic in vitro concentrations, reliance on immortalized cell lines that may not recapitulate primary-cell repair capacity, inter-laboratory variability across cytogenetic assays, and a marked scarcity of pediatric and pregnancy biomonitoring data. Most existing positive signals derive from preclinical models; clinically validated long-term outcomes, particularly carcinogenic endpoints, remain inconsistently demonstrated for most antibiotic classes outside metronidazole. Conclusions: Antibiotic-induced genotoxicity appears to be a measurable and mechanistically tractable dimension of drug safety, though its clinical magnitude in real-world exposure scenarios requires further investigation. Integrating multi-omics, microphysiological systems, single-cell genotoxicology, and AI-assisted prediction may improve risk resolution, particularly in vulnerable populations. We argue that antimicrobial stewardship discussions should consider host genome integrity alongside resistance, while remaining mindful that the mechanistic case currently outpaces clinical-endpoint validation. Full article

Background:Streptococcus agalactiae (group B Streptococcus, GBS) remains a leading cause of invasive infections in pregnant women, fetuses, and neonates. Universal screening at 36–37 weeks of gestation and intrapartum antimicrobial prophylaxis are essential to prevent adverse outcomes. This study aimed to determine the prevalence, serotype distribution, and antimicrobial susceptibility of GBS isolates among pregnant women in Greece. Methods: Vaginal and rectal swabs were collected from pregnant women undergoing GBS screening between January 2021 and December 2025. Samples were processed using Todd-Hewitt broth with colistin and nalidixic acid, and cultured on blood agar and chromogenic media. The VITEK2 system was used for GBS identification and antimicrobial susceptibility testing against penicillin, erythromycin, clindamycin, tetracycline, levofloxacin, and vancomycin, according to EUCAST guidelines. The double-disk diffusion test was used for macrolide-lincosamide-streptogramin B (MLS_B) phenotyping. Serotyping for all ten serotypes was conducted using a commercial latex agglutination assay. Results: Among 941 women screened, 118 (12.5%) were colonized with GBS. The most prevalent serotypes were III (29.7%), V (18.6%), Ib (14.4%), IX (10.2%), Ia (9.3%), and II (9.3%). All isolates were susceptible to penicillin. Resistance to erythromycin and/or clindamycin was detected in 37 isolates. In these isolates, the predominant MLS_B phenotype was constitutive (cMLS_B, 78.4%), followed by inducible (iMLS_B, 13.5%), L (5.4%), and M (2.7%) phenotypes. Conclusions: GBS colonization was detected in 12.5% of pregnant women, with serotype III predominating, underscoring its clinical relevance due to its association with invasive neonatal disease. Although penicillin remains fully effective, the observed resistance to macrolides and lincosamides, primarily mediated by the cMLS_B phenotype, raises concerns regarding alternative therapies. Full article

Background/Objectives: Acinetobacter baumannii is a major cause of infections in Intensive Care Units (ICUs), driving mortality through high-level antimicrobial resistance. This study utilized whole-genome sequencing (WGS) to evaluate the phenotypic, genotypic and virulence features of carbapenem-resistant A. baumannii (CRAB), which has caused ventilator-associated pneumonia/tracheobronchitis (VAP/VAT) in the ICU of the University Hospital of Split, Croatia. Methods: Over 1 year, lower respiratory tract specimens from 79 VAP/VAT patients were analyzed. CRAB isolates were identified via MALDI-TOF MS and evaluated for antimicrobial susceptibility, and a representative subset underwent WGS and multilocus sequence typing (MLST). Results: Out of 106 specimens, 18 non-duplicate CRAB strains were isolated. Five isolates underwent genomic analysis, identifying two globally distributed, high-risk Pasteur lineages: ST2 and ST492. These lineages displayed distinct resistomes: ST2 carried bla_OXA-23 and bla_ADC-73, while ST492 harbored plasmid-borne bla_OXA-72 (Rep3-T1/AB082 cluster) and bla_ADC-30. All isolates shared aminoglycoside/macrolide-resistance genes, conserved efflux pumps, and virulence determinants (bau, bas, ent, bar) crucial for acinetobactin synthesis and respiratory colonization. Phylogenetic analysis confirmed regional circulation and genetic links to neighboring countries. Conclusions: This study highlights the evolutionary dynamics of endemic CRAB lineages in a Croatian ICU and their global dissemination, which poses a critical threat, demanding strict infection control and novel therapeutics. Full article

(1) Background: methicillin‑resistant Staphylococcus aureus (MRSA) is a zoonotic pathogen, and its hemolysins serve as key virulence factors. Functional membrane microdomains (FMMs) are protein-enriching platforms and regulate diverse physiological functions by recruiting and assembling various proteins. However, whether and how FMMs regulate the hemolytic ability of MRSA remains unclear. This study aimed to investigate FMM-mediated regulation of MRSA hemolysins and the underlying mechanisms. (2) Methods: Homologous recombination was employed to generate FMM-disrupted (N315ΔfloA) and complemented (N315ΔfloA::floA) strains from the MRSA N315 wild-type strain (N315 WT). The three strains were compared with respect to hemolytic activity, transcript levels of key virulence and regulatory genes, and in vivo virulence. (3) Results: Disruption of FMMs significantly enhanced hemolytic activity compared with N315 WT and complemented strains. Meanwhile, FMM disruption repressed the two-component system genes (vraS and vraR), while activating the agr operon (agrB, agrD, agrC and agrA) and its effector molecule RNAIII, leading to upregulation of hemolysin genes (hla, hlb, hld). In vivo, N315ΔfloA infection markedly increased mortality in G. mellonella larvae and BALB/c mice, with significantly elevated pro-inflammatory factors (TNF-α, IL-6, and IL-1β) in mouse plasma. All these phenotypes were effectively reversed in N315ΔfloA::floA. (4) Conclusions: Disruption of FMMs potentiates both hemolytic activity and overall virulence in MRSA, with the potential underlying mechanism involving the VraS/R-Agr regulatory axis that drives transcriptional upregulation of hemolysin-encoding genes. Full article

Intracranial abscesses are extremely rare in alpacas, and previously reported cases have lacked systematic etiological characterization. The virulence characteristics of Mammaliicoccus sciuri (formerly Staphylococcus sciuri) in alpaca intracranial infections remain unclear. We investigated an alpaca with chronic otitis media and an intracranial abscess. Bacteria were recovered from intracranial purulent material and several other sites. A representative isolate was designated CS234. It was identified as M. sciuri by 16S rDNA sequencing and whole-genome sequencing (WGS). Average nucleotide identity (ANI) analysis showed 95.58% identity with M. sciuri NCTC12103. WGS identified mecA, mecA1, fexA, optrA, and sal(A). The isolate showed phenotypic resistance to aminoglycosides, tetracyclines, and macrolides. PCR screening detected several virulence-associated gene targets, including exhB and tsst-1. To our knowledge, this is the first report of exhB in M. sciuri. In an intraperitoneal mouse challenge, the median lethal dose (LD₅₀) was 4.4 × 10⁷ colony-forming units (CFU)/g body weight. Multiple-organ lesions were also observed. These findings indicate systemic pathogenic potential in mice. Recovery of M. sciuri from several affected sites indicates a strong etiological association with the suppurative disease in this alpaca. These findings expand current knowledge of M. sciuri infection and antimicrobial resistance in alpacas. They may also aid the diagnosis and treatment of similar cases. Full article

Lotus corniculatus is a superior leguminous forage with multiple values including forage, ecological, ornamental and medicinal uses. It is also an ideal material for plant bioreactors. As a core technical approach, genetic transformation overcomes the constraints of traditional breeding and facilitates the targeted improvement in stress resistance and agronomic traits in this species. This review summarizes the research progress of the Agrobacterium-mediated genetic transformation of L. corniculatus, focusing on key procedures such as explant selection, strain selection, infection and co-cultivation regimes, basal medium composition, phytohormone regulation, as well as bacteria elimination and transformant screening strategies. We further elaborate on the applications of this transformation system in enhancing tolerance to abiotic stresses (salt, drought and heat), regulating quality-related traits, and developing plant-based vaccine bioreactors. Additionally, this paper critically discusses the major bottlenecks and challenges constraining existing genetic transformation systems in L. corniculatus, and evaluates the prospects for establishing high-efficiency and genetically stable transformation platforms. This review aims to provide theoretical foundations and technical references for germplasm innovation, molecular breeding and comprehensive utilization of L. corniculatus. Full article

Ocular infections are a major cause of morbidity and vision loss worldwide, significantly affecting the quality of life and clinical outcomes. The management of ocular infections has become increasingly difficult due to the rising prevalence of antimicrobial resistance among commonly implicated pathogens. This review summarizes the epidemiology and etiology of ocular infections, with emphasis on bacterial pathogens frequently associated with resistance. Various mechanisms of antimicrobial resistance, including genetic mutations, intrinsic resistance, and biofilm formation, are also discussed. The review further examines the limitations of current therapeutics, such as poor ocular drug penetration, frequent dosing requirements, adverse effects, and reduced efficacy against multi-resistant organisms. In response to these challenges, the need for novel therapeutic approaches with improved stability and prolonged ocular retention is highlighted. Furthermore, the integration of artificial intelligence in ophthalmology is explored, particularly in disease diagnosis, image analysis, treatment planning, and antimicrobial resistance surveillance. Despite these advances, several translational challenges remain, including data set bias, limited external validation, regulatory approval hurdles, data privacy concerns, and restricted accessibility in resource-limited settings, which currently limit the widespread clinical implementation. Therefore, continued surveillance, rational antimicrobial use, and effective therapeutic strategies are essential to reduce the burden of ocular infections and improve patient outcomes. 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

Objectives: The escalation of multidrug-resistant (MDR) clinically relevant bacterial isolates, including Escherichia coli and key ESKAPE pathogens, represents a critical global healthcare threat. While antimicrobial peptides (AMPs) offer promising alternatives, metabolic instability often limits their clinical use. This study investigated the therapeutic potential, antimicrobial efficacy, and resistance dynamics of peptide D-TN6 against highly resistant bacterial strains. Methods: D-TN6 efficacy was evaluated against 164 clinical isolates, including pan-drug-resistant, carbapenem-resistant, and polymyxin-resistant phenotypes. A 20-passage serial induction assay compared resistance development kinetics of D-TN6 against gentamicin over an extended period. Results: D-TN6 demonstrated potent efficacy against MRSA (minimum inhibitory concentration (MIC)₉₀: 1 µg/mL) and remained effective against polymyxin B-resistant Klebsiella pneumoniae (MIC₉₀: 8 µg/mL) and pan-drug-resistant Acinetobacter baumannii (MIC₉₀: 8 µg/mL). In resistance assays, while the gentamicin MIC increased 256-fold by the 17th passage, the D-TN6 MIC remained constant at 1 µg/mL throughout the 20-passage study. Conclusions: These findings underscore D-TN6 as a robust therapeutic candidate. Its efficacy against MDR strains and its feature of low propensity for resistance development—likely due to membrane disruption—position D-TN6 as a promising solution for life-threatening infections where conventional last-resort agents fail. Full article

Chronic wounds are complex environments marked by persistent inflammation, oxidative stress, hypoxia, and conditions that favor antimicrobial resistance (AMR). Conventional antibiotics often fail due to bacterial persistence and the physicochemical barriers of the wound milieu. Biofilm-associated extracellular polymeric substances (EPS), efflux pump activity, quorum sensing (QS), and horizontal gene transfer (HGT) collectively drive antimicrobial tolerance and resistance dissemination, turning chronic wounds into reservoirs of multidrug-resistant pathogens. Consequently, emerging wound therapies demand multifunctional strategies that modulate the wound microenvironment while interfering with resistance-associated phenotypes. Hydrogel–metal–organic framework (MOF) composites have been explored as multifunctional interfaces that combine extracellular matrix-mimetic properties, tunable porosity, stimuli-responsiveness, and controlled therapeutic delivery with the bioactive functions of MOFs. Depending on their composition and architecture, these systems may exert antimicrobial and antibiofilm effects through ionic, electrostatic, osmotic, catalytic, and oxidative mechanisms, while also influencing ROS levels, inflammation, angiogenesis, and local drug transport. However, antimicrobial activity alone does not equate to resistance modulation. Evidence for direct effects on efflux systems, resistance phenotypes, or HGT remains inconsistent across reported platforms. This review critically examines representative hydrogel–MOF systems for chronic wound applications, comparing their composition, physicochemical properties, biological functions, proposed resistance-related mechanisms, advantages, limitations, and current level of evidence. We emphasize distinguishing experimentally demonstrated resistance-modulating effects from mechanistically proposed functions, and identifying design trade-offs and evidence gaps that must be addressed to develop wound interfaces capable of both supporting tissue regeneration and improving infection control. Full article

Background: Colistin remains an important therapeutic option for complicated urinary tract infections (cUTIs) caused by multidrug-resistant Gram-negative bacteria. A loading dose is often recommended to rapidly achieve steady-state plasma concentrations, but its clinical benefit specifically for cUTIs, where local urinary drug concentrations markedly exceed plasma levels, remains unclear. Methods: We conducted a retrospective cohort study of adult patients treated with intravenous colistin for cUTIs at Nakornping Hospital, Chiang Mai, Thailand, between 2015 and 2022. Patients were classified as receiving loading-dose (LD) or non-loading-dose (non-LD) colistin. The primary outcome was 30-day all-cause mortality. Secondary outcomes included clinical response, microbiological response, and nephrotoxicity (defined by RIFLE criteria). Inverse probability weighting (IPW) using the propensity score was applied to adjust for baseline covariates, and Cox proportional hazards regression was used to estimate crude and adjusted hazard ratios (HR) using the non-LD group as the reference. Results: Among 123 patients (74 LD, 49 non-LD), unadjusted 30-day all-cause mortality was 35.14% versus 40.82% (p = 0.524), clinical response was 75.68% versus 71.43% (p = 0.599), and microbiological response was 78.38% versus 65.31% (p = 0.109) for LD versus non-LD, respectively. Nephrotoxicity occurred in 48.65% versus 38.78% (p = 0.281). After IPW adjustment, no statistically significant differences were observed between the LD and non-LD groups for 30-day all-cause mortality (aHR 0.78, 95% CI 0.43–1.42, p = 0.419), clinical response (aOR 1.48, 95% CI 0.54–4.08, p = 0.445), or microbiological response (aOR 2.10, 95% CI 0.81–5.48, p = 0.128). For the safety outcome, nephrotoxicity was analyzed using the Fine–Gray competing risk model, treating death as a competing event. The IPW-adjusted subdistribution hazard ratio was (asHR) 2.23 (95% CI 0.83–5.95, p = 0.110), indicating no statistically significant difference in renal safety between the LD and non-LD groups. Conclusions: Loading-dose colistin was not associated with a statistically significant reduction in 30-day all-cause mortality or improvements in clinical response and microbiological eradication in patients with cUTIs. Nephrotoxicity was numerically lower without a loading dose, but the wide confidence intervals in this study of 123 patients precluded a definitive conclusion regarding renal safety. Omitting the loading dose may be a reasonable option for localized urinary infections, particularly in patients at high risk for acute kidney injury, pending confirmation in larger prospective studies. Full article

In this study, pathogenic bacteria were isolated from diseased Pelteobagrus fulvidraco collected from a yellow catfish farm in northern China. The recovered isolate was subjected to Gram staining, transmission electron microscopy observation, 16S rRNA gene sequencing and whole-genome sequencing, followed by systematic analyses of its antimicrobial resistance, pathogenicity and genomic characteristics. Combined with artificial infection assays and multiple comparative verifications, the pathogen was identified as Vibrio mimicus. Clinical observation of naturally infected fish revealed that superficial skin ulcers of varying severity constituted the hallmark clinical sign of this disease. Genomic analysis uncovered major virulence-related genes, including tlh, vmh and tdh, as well as key antimicrobial resistance genes such as crp and ugd. Artificial infection trials confirmed the strong virulence of this isolate against P. fulvidraco, with distinct clinical manifestations triggered by injections of bacterial suspensions at different concentrations. Mortality was first observed in the high-dose group at 2–3 days post-injection, yet no cutaneous ulceration was detected at this stage. The peak incidence and mortality occurred between 3 and 7 days post-challenge, with diseased fish exhibiting lesions identical to those seen in naturally infected individuals. The median lethal dose (LD₅₀) of the isolate was determined to be 1.72 × 10⁵ CFU/mL. Growth gradient assays across varying temperatures and pH values identified the optimal culture conditions for this strain: 33 °C and pH 8.5. Antimicrobial susceptibility testing demonstrated that the isolate was highly susceptible to piperacillin, norfloxacin, roxithromycin, azithromycin, furazolidone, ceftriaxone and tetracycline, whereas it displayed high-level resistance to compound sulfamethoxazole and clindamycin. Collectively, this work lays a scientific foundation for the isolation, identification and comprehensive research of Vibrio mimicus-induced ulcerative disease in yellow catfish. Full article