Search Results (86)

Bovine respiratory disease (BRD) remains one of the most consequential health and economic challenges in U.S. beef production, particularly within integrated systems where microbial, environmental, and management factors intersect. This review synthesizes contemporary epidemiological insights, emphasizing BRD’s multifactorial pathogenesis driven by dynamic host–pathogen–environment interactions involving agents such as Mannheimia haemolytica, Pasteurella multocida, and Mycoplasma bovis, alongside stressors from transportation, weaning, and commingling. BRD imposes annual losses exceeding two billion dollars through diminished feed efficiency, reduced carcass yield, increased treatment costs, and mortality. Despite progress in vaccination, biosecurity, and therapeutic interventions, BRD persists due to diagnostic subjectivity and limitations of traditional control measures. The review underscores emerging innovations, including precision livestock technologies, AI-enabled surveillance, and metabolomic biomarkers as transformative tools for early detection and targeted mitigation, while noting barriers related to cost, data harmonization, and scalability. The rising threat of antimicrobial resistance further highlights the need for stewardship frameworks that balance therapeutic effectiveness and public health priorities. Additionally, the paper analyzes policy and economic considerations, arguing for coordinated efforts among producers, veterinarians, researchers, and regulators. BRD is reframed as a systems-level challenge requiring integrated scientific, operational, and regulatory strategies to enhance resilience and sustainability across U.S. beef production. Full article

Pseudomonas aeruginosa is a resilient Gram-negative pathogen frequently implicated in healthcare associated infections, particularly among immunocompromised individuals and those with chronic conditions such as cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), or cancer. It is well known for its high resistance to antibiotic treatment. This review briefly mentions P. aeruginosa’s resistance mechanisms, biofilm formation, and virulence factors, while primarily focusing on treatment challenges and recent advancements in therapeutic strategies aimed at overcoming resistance. Covered are novel non-antibiotic interventions such as quorum sensing inhibitors, quorum quenching agents, iron chelators, lectin and efflux pump inhibitors, as well as antimicrobial peptides and nanoparticles. Traditional medicine, phytochemicals, and probiotics are also evaluated. Additionally, this review explores the development of a viable vaccine, bacteriophage therapy, lactoferrin-hypothiocyanite combination, and topical use of electrochemical scaffolds. This review emphasizes the need for extensive safety studies and in vivo validation of these emerging non-antibiotic therapeutic strategies to determine their efficacy, pharmacological behavior, and clinical feasibility before they can be translated into practice. Many of these emerging treatments could play a vital role in future combination therapies by enhancing the efficacy of existing antibiotics and countering resistance and virulence mechanisms. Advancing these approaches from laboratory to clinical application remains a major challenge, making the development of approved therapies or vaccines a critical scientific and public health priority. Full article

Non-typhoidal Salmonella (NTS) are globally distributed zoonotic pathogens of major concern within the One Health–One Biofilm framework. Fluoroquinolone-resistant Salmonella strains are included by the World Health Organization (WHO) in the Bacterial Priority Pathogens List as high-risk agents. A key virulence determinant of Salmonella is its ability to form biofilms, which may display multidrug-resistant (MDR) characteristics and contribute to bacterial persistence and treatment failure. Animals, particularly poultry and reptiles, represent important reservoirs of Salmonella, and reptile-associated salmonellosis (RAS) may manifest as extraintestinal infections in humans. In the post-antibiotic era, there is an urgent need to identify effective alternatives to conventional therapies. This review summarizes current knowledge on Salmonella biofilms, with particular attention to their MDR potential, and discusses possible strategies for their prevention and eradication, including specific immunoprophylaxis, bacteriophage therapy, and alternative antimicrobials. The promising antimicrobials include plant-based compounds/extracts, bacteriocins, fatty acids, and synthetic/semi-synthetic substances. The integration of vaccination, phage therapy, and novel anti-biofilm compounds may provide a sustainable alternative to antibiotics in controlling Salmonella infections and aligns with the principles of the One Health approach. Full article

Mesoporous silica nanoparticles (MSNs) are among the most adaptable nanocarriers in modern pharmaceutics, characterized by a high surface area, tunable pore size, controllable morphology, and excellent biocompatibility. These qualities enable effective encapsulation, protection, and the delivery of drugs in a specific area and, therefore, MSNs are powerful platforms for the targeted and controlled delivery of drugs and theragnostic agents. Over the past ten years and within the 2021–2025 period, the advancement of MSN design has led to the creation of hybrid nanostructures into polymers, lipids, metals, and biomolecules that have yielded multifunctional carriers with enhanced stability, responsiveness, and biological activities. The current review provides a review of the synthesis methods, surface functionalization techniques, and physicochemical characterization techniques that define the next-generation MSN-based delivery systems. The particular focus is put on stimuli-responsive systems, such as redox, pH, enzyme-activated, and light-activated systems, that enable delivering drugs in a controlled and localized manner. We further provide a summary of the biomedical use of MSNs and their hybrids such as in cancer chemotherapy, gene and nucleic acid delivery, antimicrobial and vaccine delivery, and central nervous system targeting, supported by recent in vivo and in vitro studies. Important evaluations of biocompatibility, immunogenicity, degradation, and biodistribution in vivo are also provided with a focus on safety in addition to the regulatory impediments to clinical translation. The review concludes by saying that there are still limitations such as large-scale reproducibility, long-term toxicity, and standardization by the regulators, and that directions are being taken in the future in the fields of smart programmable nanocarriers, green synthesis, and sustainable manufacture. Overall, mesoporous silica and hybrid nanoparticles represent a breakthrough technology in the nanomedicine sector with potentials that are unrivaled in relation to targeted, controlled, and personalized therapeutic interventions. Full article

Background/Objectives: Central nervous system (CNS) infections remain a significant public health challenge and require rapid and accurate diagnosis to guide clinical management. Although the incidence of bacterial meningitis has declined owing to widespread vaccination, viral etiologies continue to dominate CNS infections. The aim of this study was to assess the epidemiological trends, age distribution, and seasonality of CNS infections using multiplex PCR. Methods: A retrospective analysis was conducted on cerebrospinal fluid (CSF) samples collected between January 2021 and December 2022 from patients with CNS infections at King Abdulaziz Medical City. A BioFire FilmArray Meningitis/Encephalitis (ME) panel was used to detect pathogens. Patient demographics, pathogen distribution, and seasonal trends were analyzed. Results: A total of 2460 CSF samples were tested, of which 130 (5%) were positive for at least one pathogen. Viral pathogens accounted for 82.3% of the infections, with human herpesvirus-6 (HHV-6) (31%) and enterovirus (EV) (20%) being the most common. Bacterial pathogens represented 17.7% of the cases, with Streptococcus pneumoniae (6%) and Escherichia coli K1 (5%) being the predominant bacterial agents. The highest infection burden was observed in infants aged 0–6 months, with a marked male predominance. Seasonal analysis revealed multiple peaks in viral infections, particularly of HHV-6 and EVs, whereas bacterial infections were sporadic, with Streptococcus agalactiae and Streptococcus pneumoniae peaking in October and November. Conclusions: Viral infections, particularly HHV-6 and EVs, dominated CNS infections, with distinct seasonal and age-related variations. These findings underscore the value of multiplex PCR in improving the rapid diagnosis of CNS infections and aiding in timely treatment and antimicrobial stewardship. Full article

The focus of this study was to explore phage display systems employing bacteriophage lambda (λ) gene fusions to its capsid decoration protein gpD as reagent tools for tackling disease. The biological activity of gpD-fusions was examined by testing for the retained antimicrobial toxicity of cathelicidins or defensins fused to gpD. Our previous finding that only COOH fusions of either cathelicidins or defensins to gpD were toxigenic was expanded to show that only the reduced form of fused defensin antimicrobial polypeptides was found to be toxigenic. Compared in review are gene-fusion lytic display systems (where the fusion-display gene is integrated within the viral genome) with a surrogate system, employed herein, that exogenously provides the fusion-display protein for addition to phage capsid. It is easily possible to produce fully coated lambda display particles (LDP) serving as single epitope vaccines (SEV), or antimicrobials, or to produce partially coated LDP without any complex bacteriophage genetic engineering, making the system available to all. The potential to build vaccine vector phage particles (LDNAP) comprising essentially sheathed DNA vaccines encapsulated within an environmentally protective capsid is described. LDNAP are produced by introducing a cassette into the phage genome either by phage–plasmid recombination or cloning. The cassette carries a high-level eukaryotic expression promoter driving transcription of the vaccine candidate gene and is devoid of plasmid resistance elements. Full article

Over the past five decades, the emergence and re-emergence of multiple flaviviruses have triggered significant global outbreaks, posing serious threats to public health. Among them, West Nile virus (WNV) is a major cause of mosquito-borne illness, typically presenting as an acute systemic febrile disease and, in some cases, progressing to the central nervous system involvement. No specific antiviral therapies or effective vaccines are available for WNV infections. In this context, antimicrobial peptides (AMPs) with antiviral properties—known as antiviral peptides (AVPs)—have gained attention as potential therapeutic agents due to their ability to interfere with various stages of the viral life cycle. Two frog-derived melittin-like peptides, AR-23 and RV-23, were synthesized and purified, and their hemolytic activity was assessed on human erythrocytes. Antiviral activity against WNV was evaluated in Vero cells using cytopathic effect reduction assays and real-time PCR quantification of viral RNA. Time-of-addition experiments were conducted to explore the stage of viral inhibition. In silico molecular docking studies were performed to examine interactions between the peptides and the viral E glycoprotein. Both peptides displayed strong antiviral effects during the early phases of infection, likely through direct interaction with viral particles and disruption of virus–host interactions. Compared with melittin, AR-23 and RV-23 showed greater efficacy and lower cytotoxicity, highlighting their potential as promising therapeutic candidates for flavivirus infections. Full article

Campylobacter hepaticus is the etiological agent of Spotty Liver Disease (SLD), a newly emerging bacterial disease of laying hens resulting in significant mortality and production losses primarily in free-range systems. Although its economic impact continues to grow, the molecular basis of C. hepaticus pathogenesis remains poorly understood. In this study, we conducted transcriptomic profiling of C. hepaticus in three host-relevant conditions, exposure to chicken bile, infection of a chicken liver hepatocellular carcinoma (LMH) cell line, and isolation from liver lesions of naturally infected chickens. Through RNA-seq analysis, we found unique gene expression signatures in each environment. In the bile, C. hepaticus exhibited differential expression of 412 genes, with upregulation of genes related to motility, cell envelope remodeling, glycosylation, nitrate respiration, and multidrug efflux systems, indicating a stress-adaptive, metabolically active lifestyle. In LMH, on the other hand, 125 genes were differentially expressed, primarily reflecting downregulation of motility, oxidative stress response, chaperones, and core metabolic processes, suggesting that these cells adopt a less active, intracellular dormant lifestyle. Transcriptomic analysis of C. hepaticus isolated from the liver identified 26 differentially expressed genes, featuring selective upregulation of genes associated with nitrate respiration, sulfur metabolism, and pyridoxal 5’ phosphate homeostasis, alongside downregulation of the major outer membrane porin (momp), stress response chaperones (dnaK, groL), and genes involved in oxidative stress defense and energy production. Furthermore, the immune evasion-related gene cmeA and a glycosyltransferase gene were found to be highly upregulated. This study presents the first in-depth transcriptomic exploration of C. hepaticus in multiple host relevant niches. Our findings reveal niche-specific gene expression profiles and highlight metabolic and structural adaptations that enable C. hepaticus to survive during bile exposure, persist within host cells, and contribute to liver pathology. These insights provide a basis for identifying novel virulence determinants and may inform the development of targeted interventions, including vaccines or antimicrobial therapy, to control SLD in commercial poultry operations. Full article

Slaughterhouses serve as critical surveillance hubs for identifying subclinical and economically important diseases in food-producing animals. Trueperella (Arcanobacterium) pyogenes, an opportunistic pathogen commonly found on the mucous membranes of livestock, is associated with mastitis, abortion, and suppurative infections such as abscesses. In this study, we investigated 30 pig carcasses fully condemned due to vertebral osteomyelitis (VO) at two slaughterhouses in Gwangju, Republic of Korea, between November 2023 and May 2024. From abscess lesions, 11 T. pyogenes strains were isolated and characterized morphologically, biochemically, and genetically. The hemolytic exotoxin pyolysin (plo gene), a major virulence factor, was detected in five isolates (45.46%). Phylogenetic analysis of partial 16S rDNA sequences confirmed close clustering with known T. pyogenes reference strains. All 11 isolates exhibited multidrug resistance, showing resistance to 8–14 antimicrobial agents per strain. Complete resistance (11/11, 100%) was observed against amikacin (AMI), nalidixic acid (NAL), chloramphenicol (CHL), florfenicol (FFN), and trimethoprim/sulfamethoxazole (SXT). High resistance rates were also detected for erythromycin (ERY) and clindamycin (CLI) (10/11, 90.9%), ceftazidime (TAZ), ceftriaxone (AXO), ciprofloxacin (CIP) (7/11, 63.6%), and tetracycline (TET) and streptomycin (STR) (5/11, 45.5%), while gentamicin (GEN) resistance was found in three isolates (27.3%). In contrast, none of the isolates showed resistance to ampicillin, cefoxitin, or cefotaxime. These findings underscore the epidemiological value of abattoir-based monitoring in detecting emerging pathogens and tracking antimicrobial resistance. The results provide important baseline data to inform disease control strategies, guide antimicrobial stewardship, and support One Health approaches, including the development of preventive measures such as vaccines. Full article

Pneumococcal meningoencephalitis is a severe infection associated with high morbidity and mortality. Although typically community-acquired, postoperative cases following elective ENT surgery are exceedingly rare. Antimicrobial resistance (AMR) among Streptococcus pneumoniae further complicates management, and missed opportunities for vaccination represent preventable risks. We report a case of a 41-year-old man with multiple comorbidities who developed fulminant S. pneumoniae meningitis 48 h after septoturbinoplasty. The clinical course was atypical, with altered consciousness but no classical meningeal signs, necessitating urgent intubation and intensive care admission. Cerebrospinal fluid cultures identified an MDR pneumococcal strain resistant to penicillin and macrolides but susceptible to vancomycin and meropenem. Empirical therapy with vancomycin and meropenem, combined with adjunctive corticosteroids and multidisciplinary ICU care, led to complete neurological recovery. This case highlights a rare but life-threatening postoperative complication and underscores two critical lessons. First, the growing challenge of multidrug-resistant pneumococcus requires timely recognition, aggressive empiric therapy, and access to effective agents. Second, the absence of pneumococcal vaccination in this high-risk surgical patient illustrates a preventable gap in care. Integrating vaccination screening into preoperative evaluations may reduce the risk of catastrophic postoperative CNS infections. Full article

Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains one of the most devastating infectious diseases worldwide, with rising multidrug resistance limiting the effectiveness of conventional treatments. Novel therapeutic approaches are urgently needed to complement or replace existing regimens. Among emerging candidates, antimicrobial peptides (AMPs) stand out as versatile molecules capable of exerting direct antimycobacterial effects while also modulating the host immune response. This review explores peptide-based strategies against TB, with a focus on four major axes of innovation. First, we examine host-directed pathways, including the vitamin D–cathelicidin axis and other immunomodulatory mechanisms and their regulatory role in the induction of endogenous AMPs such as cathelicidin LL-37, which contributes to host-directed defense. Second, we discuss peptide-based vaccines designed to elicit robust and durable protective immunity, representing a complementary alternative to classical vaccine approaches. Third, we highlight the synergistic potential of AMPs in combination with first-line and second-line anti-TB drugs, aiming to restore or enhance bactericidal activity against resistant strains. Finally, we analyze technological platforms, including nanocarriers and inhalable formulations, that enable targeted pulmonary delivery, improve peptide stability, and enhance bioavailability. By integrating molecular design, immune modulation, and advanced delivery systems, peptide-based strategies provide a multifaceted approach to overcoming the limitations of current TB therapy. Collectively, these advances position AMPs not only as promising standalone agents but also as key components in combination and host-directed therapies, with strong potential to reshape the future clinical management of tuberculosis. Full article

Streptococcus pneumoniae has been a PCV10 vaccine-preventable agent in Bulgaria since 2010. Our objective is to determine the phylogenetic structure of 170 invasive and non-invasive pneumococcal isolates, focusing on their serotypes and antimicrobial susceptibility. Serotyping was performed using latex agglutination, capsular swelling reaction, and serotype-specific PCRs. Antibiotic susceptibilities were assessed by broth microdilution. MLST was conducted to define the clonal composition. The non-PCV10 serotypes accounted for 88.2%. The predominant invasive pneumococcal disease (IPD) serotypes were 19A (39.3%), 19F (21.4%), 6C (10.7%), 7F (7.1%), and 3 (7.1%). The prevalent NIPD serotypes were 19A (18.3%), 6C (15.5%), 3 (10.6%), 15A (7.7%), and 6A (6.3%). The overall antimicrobial non-susceptibility rates were: benzylpenicillin (55.2%), ceftriaxone (15.2%), cefuroxime (35.8%), amoxicillin-clavulanic acid (38.8%), erythromycin (60.5%), clindamycin (57.0%), tetracycline (43.5%), trimethoprim-sulfamethoxazole (62.9%), and chloramphenicol (13.5%). The multidrug resistance (MDR) strains were 60.5%. The predominant clone CC320, represented 20.0% MDR 19A and 19F strains linked to Taiwan^19F-14 and GPSC1. CC273/Greece^6B-22 and CC386 accounted for 5.3% 6A and 6C isolates. Most serotype 3 isolates are associated with CC505, associated with Netherlands³-31 and GPSC12. Switching to a conjugate vaccine with broader serotype coverage could reduce the incidence of 19A, 6C, and 15A MDR S. pneumoniae clones in our country. Full article

Neisseria gonorrhoeae is a Gram-negative diplococcus that causes gonorrhea through sexual contact. This ancient STD remains a major public health concern due to reproductive health impacts, antimicrobial resistance (AMR), and lack of a vaccine. Cannabis sativa contains antibacterial cannabinoids, though its role in combating antibiotic resistance is underexplored. The 2Fe-2S iron–sulfur cluster protein is a potential antibiotic target, as these clusters are vital for bacterial proteins involved in electron transport, enzyme activity, and gene regulation. Disrupting them may impair bacterial survival and function. In this investigation, the 2Fe–2S iron sulfur cluster binding domain-containing protein (NGFG_RS03485), identified as a potential therapeutic target from the core proteome of 12 Neisseria gonorrhoeae strains, was selected for this study. Potential antimicrobial agents were explored through molecular docking studies involving 16 cannabinoid analogs—9 obtained from literature sources and 7 identified via fingerprint similarity searches. The study revealed that four cannabinoids form favorable bonds with active regions against our targeted protein; with a high binding affinity formed from the molecular docking; 1,3-Benzenediol, 2-[3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-, (1R-trans). Dronabinol, Cannabinolic acid A (CBNA), Cannabigerolic acid (CBGA), and Ferruginene C are derivatives identified. Drug-likeness assessments were conducted to evaluate the pharmacokinetic and toxicity properties of the cannabinoids and compared against the antibiotics. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus are major respiratory pathogens associated with substantial morbidity and a risk of severe disease. However, the effectiveness of current vaccines and antiviral drugs is limited by viral mutations. Umeboshi, a traditional Japanese food prepared from pickled Prunus mume, is known for its health benefits; certain components of P. mume have exhibited antimicrobial properties. However, the efficacy of P. mume against SARS-CoV-2 and influenza virus remains unknown. We aimed to examine the antiviral activity of P. mume extracts against SARS-CoV-2 and influenza virus. Cytopathic effect (CPE) assays and reverse transcription–quantitative polymerase chain reaction (RT-qPCR) analyses with full-time treatment demonstrated that four extracts (PM2, PM3, PM4, and PM6) among eight tested inhibited the replication of both viruses. Subsequent time-of-addition assays, plaque assays, and transmission electron microscopy (TEM) confirmed that PM2 directly inactivated viral particles of both viruses by disrupting their structural integrity. Additional evaluations of virion integrity and infectivity suggested that the antiviral activity of PM2 may also involve mechanisms other than direct virion disruption. These findings suggest that P. mume-derived components exhibit direct antiviral activities against SARS-CoV-2 and influenza virus, supporting their potential development as antiviral agents or infection-preventive dietary products. Full article

A key feature that differentiates Gram-positive and Gram-negative bacteria is the outer membrane, an asymmetric membrane composed of lipopolysaccharides, phospholipids, lipoproteins and integral proteins, including the outer-membrane proteins (OMPs). By being in direct contact with the extracellular milieu, the outer membrane and OMPs participate in multiple functions in Gram-negative bacteria, including controlling nutrient and molecule access to the cytoplasm, membrane vesicle formation and resistance to environmental stresses. OMPs have a characteristic barrel shape formed by antiparallel β-strands, with or without channels that allow diffusion of substrates through the outer membrane. The marine bacterium Vibrio cholerae is responsible for non-invasive gastroenteritis and cholera disease by consumption of contaminated water or food. Its OMPs, besides having a porin function, contribute to resistance to osmotic pressure and antimicrobial agents, intracellular signaling, adhesion to host cells and biofilm formation, amongst other functions. In this review, in addition to quickly reviewing the general structure of the outer membrane, the OMPs and how they reach the outer membrane, the functions attributed to these proteins are compiled. The mechanisms used by each of the described OMP to accomplish these functions in the marine pathogenic bacterium V. cholerae are discussed. Potential clinical and bioengineering applications of OMPs, such as diagnostic tools, vaccine development, and targeted antimicrobial or anti-virulence strategies are presented. What is known about the OMPs of V. cholerae is presented below. Full article