Background and Aim: Chitosan-based DNA nanoparticles have emerged as a promising next-generation platform for veterinary vaccines, addressing several limitations of conventional attenuated, inactivated, and recombinant formulations. Chitosan is a biodegradable, biocompatible, and low toxicity polymer with mucoadhesive properties that enhance cellular uptake and protect nucleic acids from enzymatic degradation. These characteristics make it an attractive candidate for delivering plasmid DNA encoding viral antigens across diverse animal species. Recent advances demonstrate that chitosan–DNA nanoparticles can induce robust humoral and cellular immune responses, stimulate mucosal immunity, and achieve high levels of protection in terrestrial livestock, poultry, fish, and crustaceans. A wide range of viral pathogens has been targeted using this approach, including Foot-and-Mouth disease virus, Newcastle disease virus, infectious bronchitis virus, spring viremia of carp virus, white spot syndrome virus, and infectious pancreatic necrosis virus. Depending on the species and formulation strategy, nanoparticles have been successfully administered intranasally, intramuscularly, intraperitoneally, or orally, highlighting their versatility for mass vaccination in both terrestrial and aquatic systems. Reported protection rates range from 60% to 100% in mammalian and avian models, while oral nanoparticle vaccines in shrimp and fish have demonstrated sustained immune activation and survival benefits. The ability to incorporate genetic adjuvants, such as cytosine-phosphate-guanine motifs, cytokines, or complement fragments, further enhances the immunogenicity of these platforms. Despite these promising results, several challenges remain. Most studies use small laboratory animals or controlled experimental settings, and data from large-scale field trials in cattle, pigs, and equines remain scarce. The stability of nanoparticle formulations during long-term storage, the scalability of manufacturing processes, and the standardization of dosing regimens require further investigation. Overall, chitosan–DNA nanoparticles represent a safe, flexible, and rapidly adaptable vaccine carrier system with significant potential to transform veterinary immunization. Their capacity to elicit mucosal and systemic immunity, enable needle-free delivery, and support DIVA-compatible vaccine design positions them as a valuable tool for controlling emerging and re-emerging viral diseases in the context of One Health.
Nils Wetzstein, Margo Diricks, Thomas B. Anton
et al.
Abstract Background The Mycobacterium avium complex (MAC) comprises the most frequent non-tuberculous mycobacteria (NTM) in Central Europe and currently includes twelve species. M. avium (MAV), M. intracellulare subsp. intracellulare (MINT), and M. intracellulare subsp. chimaera (MCH) are clinically most relevant. However, the population structure and genomic landscape of MAC linked with potential pathobiological differences remain little investigated. Methods Whole genome sequencing (WGS) was performed on a multi-national set of MAC isolates from Germany, France, and Switzerland. Phylogenetic analysis was conducted, as well as plasmids, resistance, and virulence genes predicted from WGS data. Data was set into a global context with publicly available sequences. Finally, detailed clinical characteristics were associated with genomic data in a subset of the cohort. Results Overall, 610 isolates from 465 patients were included. The majority could be assigned to MAV (n = 386), MCH (n = 111), and MINT (n = 77). We demonstrate clustering with less than 12 SNPs distance of isolates obtained from different patients in all major MAC species and the identification of trans-European or even trans-continental clusters when set into relation with 1307 public sequences. However, none of our MCH isolates clustered closely with the heater-cooler unit outbreak strain Zuerich-1. Known plasmids were detected in MAV (325/1076, 30.2%), MINT (62/327, 19.0%), and almost all MCH-isolates (457/463, 98.7%). Predicted resistance to aminoglycosides or macrolides was rare. Overall, there was no direct link between phylogenomic grouping and clinical manifestations, but MCH and MINT were rarely found in patients with extra-pulmonary disease (OR 0.12 95% CI 0.04–0.28, p < 0.001 and OR 0.11 95% CI 0.02–0.4, p = 0.004, respectively) and MCH was negatively associated with fulfillment of the ATS criteria when isolated from respiratory samples (OR 0.28 95% CI 0.09-0.7, p = 0.011). With 14 out of 43 patients with available serial isolates, co-infections or co-colonizations with different strains or even species of the MAC were frequent (32.6%). Conclusions This study demonstrates clustering and the presence of plasmids in a large proportion of MAC isolates in Europe and in a global context. Future studies need to urgently define potential ways of transmission of MAC isolates and the potential involvement of plasmids in virulence.
ABSTRACTThe species- and clone-specific susceptibility of Staphylococcus cells for bacteriophages is governed by the structures and glycosylation patterns of wall teichoic acid (WTA) glycopolymers. The glycosylation-dependent phage-WTA interactions in the opportunistic pathogen Staphylococcus epidermidis and in other coagulase-negative staphylococci (CoNS) have remained unknown. We report a new S. epidermidis WTA glycosyltransferase TagE whose deletion confers resistance to siphoviruses such as ΦE72 but enables binding of otherwise unbound podoviruses. S. epidermidis glycerolphosphate WTA was found to be modified with glucose in a tagE-dependent manner. TagE is encoded together with the enzymes PgcA and GtaB providing uridine diphosphate-activated glucose. ΦE72 transduced several other CoNS species encoding TagE homologs, suggesting that WTA glycosylation via TagE is a frequent trait among CoNS that permits interspecies horizontal gene transfer. Our study unravels a crucial mechanism of phage-Staphylococcus interaction and horizontal gene transfer, and it will help in the design of anti-staphylococcal phage therapies.IMPORTANCEPhages are highly specific for certain bacterial hosts, and some can transduce DNA even across species boundaries. How phages recognize cognate host cells remains incompletely understood. Phages infecting members of the genus Staphylococcus bind to wall teichoic acid (WTA) glycopolymers with highly variable structures and glycosylation patterns. How WTA is glycosylated in the opportunistic pathogen Staphylococcus epidermidis and in other coagulase-negative staphylococci (CoNS) species has remained unknown. We describe that S. epidermidis glycosylates its WTA backbone with glucose, and we identify a cluster of three genes responsible for glucose activation and transfer to WTA. Their inactivation strongly alters phage susceptibility patterns, yielding resistance to siphoviruses but susceptibility to podoviruses. Many different CoNS species with related glycosylation genes can exchange DNA via siphovirus ΦE72, suggesting that glucose-modified WTA is crucial for interspecies horizontal gene transfer. Our finding will help to develop antibacterial phage therapies and unravel routes of genetic exchange.
Bloodstream infections (BSIs) are a critical medical concern, characterized by elevated morbidity, mortality, extended hospital stays, substantial healthcare costs, and diagnostic challenges. The clinical outcomes for patients with BSI can be markedly improved through the prompt identification of the causative pathogens and their susceptibility to antibiotics and antimicrobial agents. Traditional BSI diagnosis via blood culture is often hindered by its lengthy incubation period and its limitations in detecting pathogenic bacteria and their resistance profiles. Surface-enhanced Raman scattering (SERS) has recently gained prominence as a rapid and effective technique for identifying pathogenic bacteria and assessing drug resistance. This method offers molecular fingerprinting with benefits such as rapidity, sensitivity, and non-destructiveness. The objective of this study was to integrate deep learning (DL) with SERS for the rapid identification of common pathogens and their resistance to drugs in BSIs. To assess the feasibility of combining DL with SERS for direct detection, erythrocyte lysis and differential centrifugation were employed to isolate bacteria from blood samples with positive blood cultures. A total of 12,046 and 11,968 SERS spectra were collected from the two methods using Raman spectroscopy and subsequently analyzed using DL algorithms. The findings reveal that convolutional neural networks (CNNs) exhibit considerable potential in identifying prevalent pathogens and their drug-resistant strains. The differential centrifugation technique outperformed erythrocyte lysis in bacterial isolation from blood, achieving a detection accuracy of 98.68% for pathogenic bacteria and an impressive 99.85% accuracy in identifying carbapenem-resistant Klebsiella pneumoniae. In summary, this research successfully developed an innovative approach by combining DL with SERS for the swift identification of pathogenic bacteria and their drug resistance in BSIs. This novel method holds the promise of significantly improving patient prognoses and optimizing healthcare efficiency. Its potential impact could be profound, potentially transforming the diagnostic and therapeutic landscape of BSIs.
Toscana virus (TOSV), a member of the <i>Phlebovirus</i> genus transmitted by sandflies, is acknowledged for its capacity to cause neurological infections and is widely distributed across Mediterranean countries. The potential geographic distribution and risk to the human population remained obscure due to its neglected nature. We searched PubMed and Web of Science for articles published between 1 January 1971 and 30 June 2023 to extract data on TOSV detection in vectors, vertebrates and humans, clinical information of human patients, as well as the occurrence of two identified sandfly vectors for TOSV. We further predicted the global distribution of the two sandfly vectors, based on which the global risk of TOSV was projected, after incorporating the environmental, ecoclimatic, biological, and socioeconomic factors. A total of 1342 unique studies were retrieved, among which 389 met the selection criteria and were included for data extraction. TOSV infections were documented in 10 sandfly species and 14 species of vertebrates, as well as causing a total of 7571 human infections. The occurrence probabilities of two sandfly vectors have demonstrated the greatest contributions to the potential distribution of TOSV infection risk. This study provides a comprehensive overview of global TOSV distribution and potential risk zones. Future surveillance and intervention programs should prioritize high-risk areas based on updated quantitative analyses.
The use of natural polymers has increased due to concern about environmental pollution caused by plastics and emerging pollutants from fossil fuels. In this context, polysaccharides from macroalgae and microalgae arise as natural and abundant resources for various biological, biomedical, and food applications. Different nanomaterials are produced from these polysaccharides to act as effective carriers in the food and pharmaceutical industry: drug and nutrient carriers, active compound encapsulation, and delivery of therapeutic agents to tumor tissues. Polysaccharides-based nanomaterials applied as functional ingredients incorporated into foods can improve texture properties and decrease the caloric density of food products. These nanostructures also present the potential for developing food packaging with antioxidant and antimicrobial properties. In addition, polysaccharides-based nanomaterials are biocompatible, biodegradable, and safe for medical practices to prevent and manage various chronic diseases, such as diabetes, obesity, and cardiovascular disease. In this sense, this review article addresses the use of algal polysaccharides for manufacturing nanomaterials and their potential applications in food and biomedical areas. In addition, the paper discusses the general aspects of algae as a source of polysaccharides, the nanomaterials produced from these polymers, as well as recent studies and the potential use of algal polysaccharides for industries.
Climate change has an impact on agricultural activity because of its direct reliance on climate change. There are two types of relationships between agriculture and climate change, and they are extremely important, particularly for developing and underdeveloped or low-income countries, which rely heavily on agriculture for subsistence and lack adaptation infrastructure when compared to developed countries. Geographically high-latitude places that already have low temperatures might benefit from a prolonged growing season when temperatures rise due to climate change. GHG emissions such as carbon dioxide, nitrous oxide, and methane have an impact on agricultural lands. Gases have an impact on climate through emitting greenhouse gases. Emissions are mostly caused by tillage operations, fossil fuels, fertilized agricultural soils, and farm animal waste, and have a significant impact on the agriculture industry. Agriculture, on the other hand, might be a solution to climate change by lowering emissions and extensively implementing mitigation and adaptation measures. Best management approaches such as use of microbial inoculants to reduce fertilizer inputs, carbon sequestration and methane oxidation has potential to reduce greenhouse gases from agro-ecosystem.
Bruce Nzimande, John P. Makhwitine, Nompumelelo P. Mkhwanazi
et al.
The emergence of drug-resistant Human Immunodeficiency Virus-1 strains against anti-HIV therapies in the clinical pipeline, and the persistence of HIV in cellular reservoirs remains a significant concern. Therefore, there is a continuous need to discover and develop new, safer, and effective drugs targeting novel sites to combat HIV-1. The fungal species are gaining increasing attention as alternative sources of anti-HIV compounds or immunomodulators that can escape the current barriers to cure. Despite the potential of the fungal kingdom as a source for diverse chemistries that can yield novel HIV therapies, there are few comprehensive reports on the progress made thus far in the search for fungal species with the capacity to produce anti-HIV compounds. This review provides insights into the recent research developments on natural products produced by fungal species, particularly fungal endophytes exhibiting immunomodulatory or anti-HIV activities. In this study, we first explore currently existing therapies for various HIV-1 target sites. Then we assess the various activity assays developed for gauging antiviral activity production from microbial sources since they are crucial in the early screening phases for discovering novel anti-HIV compounds. Finally, we explore fungal secondary metabolites compounds that have been characterized at the structural level and demonstrate their potential as inhibitors of various HIV-1 target sites.