Search Results (11,054)

Lipopeptides (LPs) have evolved from naturally occurring compounds to key therapeutic agents against multidrug-resistant (MDR) bacterial infections. However, their expanding clinical use has triggered emerging resistance mechanisms, posing serious challenges to anti-infective therapy. This systematic review outlines the development of LP resistance and highlights innovative strategies to counteract it. To overcome these evolving barriers, the field has transitioned from traditional empirical optimization to multidimensional rational design. Moving beyond conventional structure–activity relationship (SAR)-guided chemical synthesis, current approaches integrate diverse innovative methodologies. Based on these advances, this review provides the first systematic summary of contemporary strategies for developing novel LPs, offering new perspectives and methodological support to combat resistant bacterial infections and accelerate the development of next-generation LP-based therapeutics. Full article

Bovine mastitis remains a major challenge in dairy production despite extensive antimicrobial use, with therapeutic failure increasingly attributed to factors beyond classical antimicrobial resistance (AMR). Growing evidence indicates that treatment inefficacy arises from the combined effects of pharmacokinetic/pharmacodynamic (PK/PD) constraints, biofilm-mediated tolerance, intracellular persistence, and the adaptive capacity of mastitis pathogens. Intramammary therapy is particularly limited by poor tissue penetration, episodic drug elimination via milk flow, and inactivation by milk components, frequently resulting in subtherapeutic exposure at the site of infection. These limitations are amplified in chronic and subclinical mastitis, where biofilms and intracellular reservoirs reduce antimicrobial susceptibility and promote relapse and resistance selection. This narrative review integrates current knowledge on pharmacokinetic and pharmacodynamic (PK/PD) barriers, microbial survival strategies, and antimicrobial resistance (AMR) mechanisms that underlie treatment failure in bovine mastitis. It critically evaluates conventional antimicrobial therapies alongside emerging approaches, including antimicrobial peptides, bacteriophages and endolysins, nanoparticle-based delivery systems, immunomodulators, CRISPR-guided antimicrobials, and drug repurposing strategies. Overall, available evidence highlights the potential of these approaches to enhance therapeutic durability, particularly in settings where biofilm formation, intracellular persistence, and resistance limit conventional treatment efficacy. By mapping research coverage across mastitis phenotypes and therapeutic outcomes, this review identifies key gaps in long-term efficacy and resistance mitigation and underscores the need for PK/PD-guided, biofilm-aware, and resistance-conscious strategies to support durable next-generation mastitis management. Full article

Klebsiella oxytoca has emerged as an important opportunistic pathogen in nosocomial infections, particularly during the COVID-19 pandemic, due to its capacity to acquire and disseminate resistance and virulence genes through horizontal gene transfer (HGT). This study presents a genome-based comparative analysis of K. oxytoca within the genus Klebsiella, aimed at exploring the evolutionary plausibility of outer membrane vesicle (OMV) associated processes in bacterial adaptation. Using publicly available reference genomes, we analyzed pangenome structure, phylogenetic relationships, and the distribution of mobile genetic elements, resistance determinants, virulence factors, and genes related to OMV biogenesis. Our results reveal a conserved set of envelope associated and stress responsive genes involved in vesiculogenic pathways, together with an extensive mobilome and resistome characteristic of the genus. Although these genomic features are consistent with conditions that may favor OMV production, they do not constitute direct evidence of functional OMV mediated horizontal gene transfer. Instead, our findings support a hypothesis generating evolutionary framework in which OMVs may act as a complementary mechanism to established gene transfer routes, including conjugation, integrative mobile elements, and bacteriophages. Overall, this study provides a genomic framework for future experimental and metagenomic investigations into the role of OMV-associated processes in antimicrobial resistance dissemination and should be interpreted as a recently identified evolutionary strategy inferred from genomic data, rather than a novel or experimentally validated mechanism. Full article

Gastrointestinal nematode (GIN) infections are the most prevalent parasitic diseases in grazing sheep worldwide, causing significant productivity losses, high mortality and, as a result, economic losses and emerging animal welfare concerns. Conventional control strategies, primarily relying on anthelmintic treatments, face limitations due to rising drug resistance and environmental concerns, underscoring the need for sustainable alternatives. Selective breeding for host genetic resistance has emerged as a promising strategy, while recent advances in transcriptomics and integrative omics research are providing deeper insights into the immune pathways and molecular and genetic mechanisms that underpin host–parasite interactions. This review summarizes current evidence on transcriptomic signatures associated with resistance and susceptibility to H. contortus and T. circumcincta GIN infections, highlighting candidate genes, functional genetic markers, key immune pathways, and regulatory networks. Furthermore, we discuss how other omics approaches, including genomics, proteomics, metabolomics, microbiome, and multi-omics integrations, provide perspectives that enhance the understanding of the complexity of the GIN resistance trait. Transcriptomic studies, particularly using RNA-Sequencing technology, have revealed differential gene expression, functional genetic variants, such as SNPs and INDELs, in expressed regions and splice junctions, and regulatory long non-coding RNAs that distinguish resistance from susceptible sheep, highlighting pathways related to Th2 immunity, antigen presentation, tissue repair, and stress signaling. Genomic analyses have identified SNPs, QTL, and candidate genes linked to immune regulation and parasite resistance. Proteomic and metabolomic profiling further elucidates breed- and tissue-specific alterations in protein abundance and metabolic pathways, while microbiome studies demonstrate distinct microbial signatures in resistant sheep, suggesting a role in modulating host immunity. In conclusion, emerging multi-omics approaches and their integration strategies provide a comprehensive framework for understanding the complex host–parasite interactions that govern GIN resistance, offering potential candidate biomarkers for genomic selection and breeding programs aimed at developing sustainable, parasite-resistant sheep populations. Full article

Methicillin-resistant Staphylococcus aureus (MRSA) is a significant pathogen in both healthcare-associated (HA-MRSA) and community-associated (CA-MRSA) infections, posing major challenges due to its evolving antimicrobial resistance (AMR) and genetic diversity. This study investigates the prevalence, antimicrobial resistance patterns, and molecular characteristics of HA-MRSA and CA-MRSA isolates in Saudi Arabia. A retrospective analysis was conducted on 178 MRSA isolates obtained from clinical samples. MRSA identification was performed using cefoxitin disk diffusion, and antimicrobial susceptibility testing for vancomycin, linezolid, and ciprofloxacin was conducted using the BD Phoenix M50 system. Molecular characterization included SCCmec typing, spa typing, and PCR-based detection of virulence genes (pvl, tst, eta, etb, lukS, lukF). Statistical analysis was carried out using SPSS, with a significance threshold of p < 0.05. Among 1496 S. aureus isolates, 178 (11.9%) were confirmed as MRSA, with HA-MRSA (61.8%) being more prevalent than CA-MRSA (38.2%). Notably, 7.8% of HA-MRSA isolates exhibited heteroresistant vancomycin-intermediate S. aureus (hVISA). Ciprofloxacin resistance was significantly higher in HA-MRSA (85.0%) compared to CA-MRSA (38.9%). SCCmec type V was the predominant genotype (87.1%), suggesting increased infiltration of CA-MRSA strains into hospital settings. Spa typing revealed high genetic diversity, with t037 being the most common (27%). Virulence genes were detected in 6% of isolates, indicating limited dissemination of these factors. The findings highlight the increasing prevalence of MRSA, the emergence of hVISA, and shifts in clonal distribution, underscoring the need for ongoing molecular surveillance and stringent antimicrobial stewardship programs to control MRSA spread in both healthcare and community environments. Full article

Background/Objectives: The COVID-19 pandemic profoundly disrupted gastric cancer care, reducing access to screening, delaying diagnosis, and altering therapeutic pathways worldwide. Beyond clinical challenges, it exposed structural weaknesses in healthcare systems but also accelerated innovation. Methods: We conducted a narrative review supported by a structured literature search (PubMed/MEDLINE, Scopus, Web of Science; 1 January 2014–30 November 2025), with a narrative synthesis of observational studies, registry analyses, and meta-analyses addressing COVID-19–related changes in gastric cancer epidemiology, diagnosis, treatment, vaccination, and telemedicine. A PRISMA-style flow diagram was used to illustrate study selection. Results: Elective endoscopy volumes fell by up to 80%, leading to diagnostic backlogs and increased proportions of advanced-stage gastric cancer. Surgical postponements, modified chemotherapy and radiotherapy schedules, and reduced molecular/genetic testing further compromised outcomes. Conversely, vaccination, telemedicine, capsule endoscopy, and adaptive triage frameworks enabled partial recovery of services. Geographical variations were observed in the recovery of gastric cancer care services, with regions that had established screening infrastructure generally resuming activity more rapidly, whereas others experienced ongoing delays and diagnostic backlogs. Conclusions: This review integrates epidemiological, diagnostic, and therapeutic evidence to demonstrate how COVID-19 redefined gastric cancer care. By highlighting regional disparities and outlining a conceptual model for oncologic resilience, it provides an innovative framework for future crisis preparedness. The lessons of the pandemic—digital health integration, flexible treatment protocols, and international collaboration—represent a foundation for more robust, equitable gastric cancer management in the post-pandemic era. Full article

Candidozyma auris (previously named Candida auris) has been recognized as a significant public health threat due to its extensive transmission in hospital settings, high mortality rates, and multidrug resistance. Evidence regarding optimal antifungal treatment in children remains limited. The present systematic review aims to synthesize available evidence on pediatric C. auris infections, focusing on antifungal treatment, resistance profiles, and clinical outcomes. A systematic search was conducted across PubMed, Scopus, and Web of Science, identifying case reports and case series of pediatric patients with confirmed C. auris infection. Data were extracted on demographics, comorbidities, infection site, antifungal therapy, and outcomes. Risk of bias was assessed using JBI Critical Appraisal checklists. Fourteen studies comprising 62 patients were included, with most cases being bloodstream infections. C. auris showed widespread fluconazole resistance and variable susceptibility to amphotericin B. Echinocandins were the most commonly used agents, generally associated with survival. Overall mortality was 35%, similar to that reported for adults. Combination therapy showed numerically higher survival, although given the small sample size and heterogeneity of treatment regimens, no comparative inferences can be made. Pediatric C. auris infections mirror adult patterns of antifungal resistance and mortality. Echinocandins remain first line therapy; however, the emergence of echinocandin resistance underscores the urgent need for antifungal stewardship, standardized pediatric guidelines, and novel antifungal development. Full article

Purpose: Chronic Obstructive Pulmonary Disease (COPD) is a progressive respiratory condition often accompanied by various comorbidities that significantly affect patient outcomes. High resolution computed tomography (HRCT) has emerged as a valuable tool for diagnosing and managing COPD-related comorbidities. This study aimed to explore the impact of chest computed tomography (CT) imaging in identifying and characterizing comorbidities in COPD patients. Methods: The study was conducted on 99 patients with COPD, the median age of the study population was 70.0 years (Q1–Q3: 62.0–75.0); 86% were men (85), and 14% were women (14). All patients underwent chest HRCT to identify the presence of comorbidities. Results: According to the GOLD classification (ABE groups), 3% were type A, 27% were type B, and 69% were type E. The prevalence of comorbidities identified on chest HRCT was reported as 66% for coronary artery calcification (CAC), 83% for osteoporosis, 36% for pulmonary artery enlargement (PAE), 31% for emphysema, 19% for bronchiectasis, 17% for hiatal hernia, 14% for lung cancer, 12% pulmonary infections, and 3% for interstitial abnormalities. In 4%, there were no comorbidities, one comorbidity was found in 11%, two comorbidities in 17%, and three comorbidities and more in 68% of cases. Conclusions: Chest HRCT imaging serves as a valuable tool for identifying and assessing comorbidities in patients with COPD. Incorporating chest CT imaging into the routine evaluation of COPD patients may contribute to a more comprehensive understanding of their condition and lead to better clinical outcomes. Full article

Asian soybean rust (ASR), caused by Phakopsora pachyrhizi (Syd.), poses a serious threat to global soybean production. The main approach to managing this disease has been through repeated fungicide applications which have reduced efficacy due to fungicide resistance. Recently, spray-induced gene silencing (SIGS) through exogenous application of double-stranded RNA (dsRNA) has emerged as a promising approach for plant disease management. In the present study, twelve different dsRNAs targeting genes important for P. pachyrhizi urediniospore germination, infection of the host plant or resistant to commonly used fungicides were produced in Escherichia coli on a large scale. Nine of these dsRNAs significantly reduced ASR severity (by 24.0% to 81.1%) and fungal biomass (50.5% to 83.1%) compared to the control when applied as a foliar spray in our growth chamber studies. Three of the most effective dsRNAs targeting an acyltransferase (ACE), cytochrome B (CYTB1) and a reductase (S12) also significantly reduced disease severity (78.2 to 82.3%) and fungal growth (79.8 to 85.4%) compared to the control in the greenhouse studies. Further investigation of the P. pachryrhizi urediniospore germination and hyphal growth in the presence of these dsRNAs in vitro revealed these dsRNAs reduced the spore germination rate from 72.1% to 0.0–26.6% at 4.5 h and hyphal growth from 254.0 µm to 2.7–40.5 µm at 9 h, with dsRNA targeting the S12 gene being the most effective. These results highlight the potential of SIGS using selected dsRNAs as a sustainable strategy for managing ASR through suppressing urediniospore germination and hyphal growth. Full article

As an emerging threat to global food security, wheat blast necessitates the development of a rapid and field-deployable detection system to facilitate early diagnosis, enable effective management, and prevent its further spread to new regions. In this study, we aimed to validate and improve a Recombinase Polymerase Amplification coupled with PCRD lateral flow detection (RPA-PCRD strip assay) kit for the rapid and specific identification of Magnaporthe oryzae pathotype Triticum (MoT) in field samples. The assay demonstrated exceptional sensitivity, detecting as low as 10 pg/µL of target DNA, and exhibited no cross-reactivity with M. oryzae Oryzae (MoO) isolates and other major fungal phytopathogens under the genera of Fusarium, Bipolaris, Colletotrichum, and Botrydiplodia. The method successfully detected MoT in wheat leaves as early as 4 days post-infection (DPI), and in infected spikes, seeds, and alternate hosts. Furthermore, by combining a simplified polyethylene glycol-NaOH method for extracting DNA from plant samples, the entire RPA-PCRD strip assay enabled the detection of MoT within 30 min with no specialized equipment and high technical skills at ambient temperature (37–39 °C). When applied to field samples, it successfully detected MoT in naturally infected diseased wheat plants from seven different fields in a wheat blast hotspot district, Meherpur, Bangladesh. Training 52 diverse stakeholders validated the kit’s field readiness, with 88% of trainees endorsing its user-friendly design. This method offers a practical, low-cost, and portable point-of-care diagnostic tool suitable for on-site genomic surveillance, integrated management, seed health testing, and quarantine screening of wheat blast in resource-limited settings. Furthermore, the RPA-PCRD platform serves as an early warning modular diagnostic template that can be readily adapted to detect a wide array of phytopathogens by integrating target-specific genomic primers. Full article

Background: We report an uncommon presentation of Lyme disease and highlight the importance of a detailed history in a patient with new-onset sixth nerve palsy. Methods: Case report and literature review. Results: A 46-year-old man receiving infliximab presented to the ophthalmology emergency department with horizontal binocular diplopia. History revealed a diffuse headache that had begun three weeks earlier. Ophthalmologic examination demonstrated a left sixth cranial nerve palsy. The workup showed positive Borrelia serum IgG, which was interpreted as a likely false-positive result given the limited specificity of serologic testing. At follow-up, the patient reported left-sided peripheral facial palsy, and worsening headache and diplopia. Further history revealed prior erythema migrans treated with doxycycline four months earlier. Considering these new findings, a lumbar puncture was performed and demonstrated intrathecal production of Borrelia antibodies. Neuroborreliosis, a neurologic involvement secondary to systemic infection by the spirochete Borrelia burgdorferi, was diagnosed. The patient was treated with oral doxycycline for 28 days with complete resolution of symptoms. Conclusions: Lyme disease may present with progressive neuro-ophthalmologic symptoms, underscoring the crucial role of ophthalmologists in its diagnosis. Moreover, immunosuppression may delay diagnosis and allow neurological progression, highlighting the need for careful history taking and close follow-up. Full article

The emergence of SARS-CoV-2 posed a great global threat and emphasized the urgent need for diagnostic tools that are rapid, reliable, sensitive and capable of real-time monitoring of SARS-CoV-2 infections. Recent investigations have identified a potential connection between SARS-CoV-2 infection and gut dysbiosis, highlighting the sophisticated interplay between the virus and the host microbiome. This review article discusses the eminence of nanobiosensors, as state-of-the-art tools, to investigate and clarify the connection between SARS-CoV-2 pathogenesis and gut microbiome imbalance. Nanobiosensors are uniquely advantageous owing to their sensitivity, selectivity, specificity, and reliable monitoring capabilities, making them well-suited for identifying both viral particles and microbial markers in biological samples. We explored a range of nanobiosensor platforms and their potential use for concurrently monitoring the gut dysbiosis induced by different pathological conditions. Additionally, we explore how advanced sensing technologies can shed light on the mechanisms driving virus-induced dysbiosis, and the implications for disease progression and patient outcomes. The integration of nanobiosensors with microfluidic devices and artificial intelligence algorithms has also been explored, highlighting the potential of developing point-of-care diagnostic tools that provide comprehensive insights into both viral infection and gut health. Utilizing nanotechnology, scientists and healthcare professionals may gain a more profound insight into the complex interaction dynamics between SARS-CoV-2 infection and the gut microenvironment. This could pave the way for enhanced diagnostic and prognostic approaches, treatment courses, and patient care for COVID-19. Full article

Immunotherapy, especially immune checkpoint inhibitors (ICIs), has become one of the core therapeutic approaches in cancer in recent years. It demonstrates remarkable efficacy in the treatment of melanoma and lung cancer. Conversely, its use in treating gastric cancer (GC) is not associated with considerable benefits. The high heterogeneity of GC and the tumor microenvironment (TME) may directly influence this phenomenon. This review focuses on the correlation between Helicobacter pylori (H. pylori) infection, gastric physiology, and molecular subtype-specific induction pathways, with emphasis on the unique metabolic features of GC. It explores the connection of H. pylori infection, gastric physiologic functions, and molecular subtype-specific induction mechanism of GC with the special metabolism of GC. It also explains the relationship between immune metabolic reprogramming and the suppressive TME in GC. Crucially, we summarize emerging therapeutic strategies targeting metabolic vulnerabilities. Furthermore, we explore the potential of subtype-guided metabolic therapies to overcome the challenges of the immunosuppressive tumor microenvironment in GC. Full article

Piscine lactococcosis is an emerging bacterial disease that threatens freshwater and marine aquaculture in the Mediterranean region. This study characterized isolates of Lactococcus garvieae and Lactococcus petauri from farmed fish through molecular identification, genomic typing and antimicrobial susceptibility testing. A total of 39 bacterial strains were analyzed using species-specific real-time PCR assays, multilocus sequence typing and broth microdilution to determine minimum inhibitory concentrations. Results suggest a temporal shift in freshwater systems, where L. garvieae predominated in earlier isolates (mainly ST13, CC4), while L. petauri (ST14, CC14) appears as the dominant species in recent years. In marine fish, only L. garvieae was detected, mainly ST95 (CC95), a lineage previously reported in Europe. Molecular variability was found in both species with lineages capable of infecting livestock and humans. Amoxicillin displayed promising results; florfenicol showed moderate activity, while flumequine exhibited no inhibitory effect. Oxytetracycline and trimethoprim–sulfamethoxazole showed variable results requiring prudent use. These region-specific susceptibility profiles provide updated baseline data to guide empirical antimicrobial therapy while awaiting laboratory confirmation, highlighting the evolution of lactococcosis in aquaculture and emphasizing the need for molecular surveillance, antimicrobial stewardship, and vaccine updates within a One Health framework to mitigate impacts on Mediterranean aquaculture and public health. Full article

Bacteriophage (phage) therapy, including monophage preparations, phage cocktails, engineered phages, and phage-derived enzymes, has re-emerged as a potential option for difficult-to-treat and biofilm-associated infections in the context of rising antimicrobial resistance. Recent scientific and regulatory developments, such as the 2024 World Health Organization Bacterial Priority Pathogens List and the introduction of the European Pharmacopoeia general chapter 5.31 on phage therapy medicinal products, highlight the growing interest in establishing quality, safety, and governance standards for clinical implementation. This narrative review provides an overview of current clinical applications of phage therapy, drawing on published case reports, case series, early-phase clinical studies, and regulatory experiences across different healthcare settings. Clinical use has been reported in respiratory, urinary tract, musculoskeletal, cardiovascular, and device-associated infections, particularly in cases involving multidrug-resistant pathogens, often in combination with antibiotics. At the same time, the biological characteristics of phages, such as strain specificity, adaptive composition of phage cocktails, and the need for individualized formulations, pose significant regulatory and translational challenges. Access to phage therapy currently relies on heterogeneous regulatory mechanisms, including compassionate use programmes, magistral preparations, named-patient pathways, and other national frameworks. Overall, phage therapy represents a promising strategy for selected infections, but its broader clinical adoption will depend on harmonized regulatory approaches, robust quality standards, and the generation of stronger clinical evidence to support safe and scalable use. Full article