Engineered microbes are emerging as a new class of living immunotherapeutics. Unlike conventional biologics or cell therapies with fixed mechanisms, these systems can sense and respond to dynamic tissue environments. They integrate environmental, metabolic, and immunological cues and process these signals through programmable biological circuits, executing context-dependent immune modulation with spatial and temporal precision. This review proposes an immune-centered paradigm shift for understanding engineered microbes. We conceptualize them as distributed immune-computational systems composed of sensing, signal processing, memory, and effector modules embedded within host immune networks. Rather than organizing the field by microbial taxonomy or disease category, we focus on immune logic. We describe how engineered microbes detect immune state signals, interpret these inputs through synthetic circuits, and generate outputs that activate, suppress, educate, or reprogram immunity. Applications across cancer, autoimmunity, and infection are discussed with attention to disease-specific immune requirements. We further define immune safety architecture as a core design principle, which includes inflammatory control, tolerance preservation, adaptive regulation, and mechanisms for therapeutic termination. Finally, we outline translational and regulatory considerations, emphasizing immune state-resolved evaluation rather than static pharmacologic endpoints. Together, this paradigm shift positions engineered microbes as programmable immune-modulating systems and provides a conceptual foundation for the rational development of next-generation living immunotherapies.
With the escalating crisis of antimicrobial resistance, the slow pace of traditional antibiotic development presents a critical and growing threat to global public health. Phage therapy, which offers benefits such as high specificity, self-replication, and minimal disruption to the microbiota, has emerged as a promising treatment option. However, its therapeutic potential faces several hurdles, including a limited antibacterial spectrum, inadequate in vivo efficacy, susceptibility to immune clearance, and inability to target intracellular bacteria and biofilm-associated infections. To overcome these issues, new delivery systems have been developed by combining engineered phages with functional materials, such as nanomaterials, hydrogels, and liposomes. This approach significantly improves phage targeting, stability, drug delivery capacity, and controlled release. Nevertheless, engineered phages face challenges such as complex host interactions and intestinal delivery. Future research should incorporate artificial intelligence-assisted design, cross-disciplinary teamwork, and innovative materials to develop phage delivery systems as groundbreaking tools against drug-resistant infections and complex diseases. This review discusses the potential uses of engineered phages in combination with antibiotic therapy, clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein gene editing, innovative smart drug delivery, and tumor immune environment control. It also examines the key challenges in translating laboratory studies to clinical use, including technical issues, immune response regulation, and safety concerns.
The relentless spread of antimicrobial-resistant Escherichia coli underscores the critical need for alternative therapeutics, such as bacteriophages. A major translational hurdle is the efficient and safe initial isolation of lytic phages with defined therapeutic potentials. This study established and validated a safety-conscious pipeline using the non-pathogenic laboratory strain E. coliDH5α (BSL-1) for environmental phage screening, a strategy designed for accessibility and to circumvent early biosafety concerns. After continuous screening, we isolated a novel lytic phage, vB_EcoS_NLE251, from the soil. Comprehensive phenotyping revealed robust stability (tolerant up to 60 °C) and efficient replication, with an optimal multiplicity of infection (MOI) of 100, yielding a high titer of 2.1 × 1010 PFU/mL. Crucially, host-range determination using a panel of 35 clinical E. coliisolates showed that NLE251 only exhibited lytic activity in spot assays against a single biliary tract infection-derived strain (54959124), though subsequent quantitative infection efficiency data indicate extremely low productive infection against this target strain. Genomic analysis (49,336 bp dsDNA, belonging to the class Caudoviricetes) further confirmed the absence of virulence or antibiotic resistance genes, fulfilling a key safety prerequisite for therapeutic use. Although NLE251 is a narrow-spectrum agent, this study provides a validated methodological framework that prioritizes safety and specificity from the initial isolation step, offering a safety-prioritized, standardized pipeline for accelerating phage discovery against multidrug-resistant bacterial infections.
Human immunodeficiency virus (HIV) is a pathogenic virus capable of entering the human body and replicating within T cells, ultimately leading to acquired immunodeficiency syndrome. In contrast, GB-virus C (GBV-C), a member of the Flaviviridae family, also infects humans but, according to current studies, is not associated with any known pathogenic effects. Unlike most RNA viruses, GBV-C encodes a single polyprotein. It is primarily transmitted through blood and sexual contact. GBV-C comprises three strains: GBV-C, hepatitis G virus (HGV), and other less-studied strains. The HGV strain has been detected in patients with liver cirrhosis; however, there is no evidence that it causes liver disease. Notably, GBV-C reduces immune activation in HIV-infected patients. It has been shown to have a significant effect on the target cell receptors for HIV, indicating its potential as a model for vaccine development against HIV. However, there is a lack of information and studies concerning this virus. GBV-C-based vaccine development faces many challenges, such as concerns about safety and efficacy, limited understanding of its mechanisms of action and immunogenicity, HIV strain variability, ethical and regulatory considerations, production and delivery logistics, long-term outcomes, and public perception and acceptance. Nevertheless, bioinformatic techniques can play a crucial role in overcoming these challenges through approaches such as comparative genomics, epitope mapping, structural bioinformatics, and vaccine design and optimization.
Erythropoietin-producing hepatocellular (Eph) receptor A5 (EphA5) binds to ephrin ligands and initiates intracellular signaling through its tyrosine kinase activity. EphA5 is upregulated or mutated in various tumors, and these alterations are associated with tumor progression and sensitivity to immunotherapy, respectively. Therefore, EphA5 has been proposed as an attractive target for tumor diagnosis and therapy. A monoclonal antibody (mAb) against EphA5 is essential for basic research and for the development of mAb-based tumor therapies. In this study, we developed a novel anti-human EphA5 mAb, Ea5Mab-7, using the Cell-Based Immunization and Screening (CBIS) approach. Ea5Mab-7 reacted with EphA5-overexpressed Chinese hamster ovary-K1 (CHO/EphA5), EphA5-overexpressed glioblastoma LN229 (LN229/EphA5), and Saos-2 osteosarcoma cells endogenously expressing EphA5, as assessed using flow cytometry. The binding affinities (KD values) were determined to be 3.2 × 10−9 M for CHO/EphA5, 3.0 × 10−9 M for LN229/EphA5, and 1.3 × 10−9 M for Saos-2. Furthermore, Ea5Mab-7 did not exhibit cross-reactivity with other ephrin receptor-overexpressed CHO-K1 cells. In addition, Ea5Mab-7 was suitable for immunohistochemistry. These results indicate that Ea5Mab-7, established using the CBIS method, facilitates basic studies of EphA5 and is a potential candidate for mAb-based tumor diagnosis and therapy.
The effectiveness of macrolides in the treatment of pneumococcal infections has been increasingly challenged by the emergence and spread of antibiotic resistance mechanisms. This study aims to determine the prevalence of macrolide resistance genes (mefA and ermB) among Streptococcus pneumoniae isolates from selected regions of Indonesia. A total of 703 archived S. pneumoniae isolates were screened for both genes using polymerase chain reaction. A total of 11% and 4% isolates were positive for mefA and ermB, respectively. The major serotype carrying the mefA gene was 19F (48%), followed by serotype 23F (39%). The predominant serotype containing the ermB genes was 19F (17%). The occurrence of macrolide resistance in S. pneumoniae in Indonesia shows a notable pattern, with the most prominent presence observed in serotype 19F.
The cold environments serve as life-entrapping reservoirs of diverse life forms, ranging from eukaryotes to diverse microbial inoculi. Actinobacteria are omnipresent in cold environments, and their existence is notably linked to a remarkable potential for producing and harboring unique metabolites. Their ability to survive in such extreme conditions is supported by a range of adaptations tailored to their specific niche, including cold-resistant traits. In this review, we summarize recent advances (2017–2025) regarding psychrophilic actinobacteria, focusing on newly identified species and novel compounds reported in the literature. Notably, we highlight the discovery of 44 new species as well as nine new compounds across various actinobacteria genera. The inventory of abiotic hurdles associated with cold environments positions this field as a potential hotspot and emerging frontier for sourcing pharmaceutical-like compounds of exceptional ingenuity and complexity. By providing an overview of the recent discoveries in psychrophilic actinobacteria and their intriguing metabolites, this review aims to offer valuable insights to facilitate bioprospecting efforts in cold ecosystems.
In low-resource clinical microbiology laboratories, the identification of non- fermenting, oxidase-positive Gram-negative bacilli remains a significant challenge. Due to limited diagnostic capabilities, there is a pervasive tendency to report all such organisms simply as Pseudomonasspecies, often implicitly considered Pseudomonas aeruginosa. This practice overlooks the vast diversity within the Pseudomonadaceae family, which includes numerous genera such as Burkholderia, Stenotrophomonas, Achromobacter, Ochrobactrum, Ralstonia, and many non-aeruginosa Pseudomonas spp. This misidentification poses serious clinical consequences, as intrinsic antibiotic resistance profiles vary dramatically across these species, leading to inappropriate therapy and treatment failure. Furthermore, it curtails effective epidemiological surveillance and source investigation during outbreaks. This paper delineates the scope of this problem, its impact on patient care and public health, and proposes a multifaceted, feasible way forward for laboratories constrained by resources. With this, the author calls for the adoption of stratified, algorithmic approaches using basic biochemical tests and enhanced training, as well as the strategic development of affordable, context-specific diagnostic solutions.
Nosocomial infections (NIs) are a significant global health issue, specifically in intensive care units (ICUs). The study aims to identify the bacterial profiles and antimicrobial resistance patterns of NI pathogens in the ICU of a tertiary care hospital, with the goal of informing effective treatment and infection control approaches. This cross-sectional, descriptive study was conducted between March 2024 and March 2025 in the ICUs of Saidu Teaching Hospital. Clinical samples were collected from patients who had acquired signs of infection after 48 h of admission. Identification and antimicrobial susceptibility of bacteria were conducted using standard microbiological and Kirby–Bauer disc diffusion techniques. Multidrug resistance (MDR) was defined as non-susceptibility to at least one agent in three or more antimicrobial categories. Among 450 admitted patients, 112 (24.9%) had clinical NIs, and 98 (21.8%) were microbiologically verified. Gram-negative bacilli predominated (78.6%), followed by Acinetobacter baumannii (27.7%) and Pseudomonas aeruginosa (21.4%). Ventilator-associated pneumonia (45.5%) and catheter-associated urinary tract infections (28.6%) were the most common sites of infection. The prevalence of MDR was alarming, 76.8% overall, with 100% of A. baumannii and K. pneumoniae being MDR. Carbapenem resistance was found to be high (A. baumannii: 93.5, K. pneumoniae: 72.2). Most Gram-negative isolates were mostly susceptible to colistin. NIs tend to have a high burden in the ICU, as observed in this study, particularly with Gram-negative bacteria that exhibit MDR. The extreme prevalence of carbapenem-resistant A. baumannii and K. pneumoniae signals an highlights a crisis in antimicrobial resistance. These findings underscore the importance of implementing robust infection prevention and control policies, executing rigorous antibiotic stewardship initiatives, and maintaining ongoing local surveillance to inform empirical treatment and improve patient outcomes.
Arboviral diseases are escalating across South Asia, with ecological and socioeconomic factors positioning the region as a potential global pandemic epicenter. Traditional pathogens such as dengue, chikungunya, and Japanese encephalitis persist alongside emerging threats such as Zika, severe fever with thrombocytopenia syndrome (SFTS), Tamdy, and Karshi viruses, are all expanding geographically. Climate change accelerates vector range shifts, while rapid urbanization, inadequate healthcare infrastructure, cross-border mobility, and fragmented surveillance amplify transmission risks. High population density, limited vector control, and low vaccination coverage create ideal conditions for viral spread and recombination. Recent outbreaks reveal alarming trends, including expanded vector habitats, increased disease severity, and record-breaking epidemic rates. Without coordinated regional strategies integrating enhanced surveillance, vector management, and healthcare capacity building, South Asia’s arboviral burden could catalyze global health crises. This synthesis underscores the urgent need for multidisciplinary interventions to address the complex drivers of arboviral proliferation in this vulnerable region.
Herpes simplex virus type 1 (HSV-1) remains a widespread human pathogen responsible for recurrent infections and significant health burdens. The emergence of drug resistance and limitations of existing antiviral therapies highlight the need for the development of novel antiviral agents with improved efficacy and safety profiles In this study, a library of novel 1,2,4-triazole derivatives fused with a pyrazine moiety (5a–5t) was successfully synthesized and evaluated for their therapeutic potential against HSV-1 and oxidative stress. These compounds were assessed for anti- inflammatory, antioxidant, and anti-HSV–1 activities, demonstrating encouraging biological profiles. In particular, compounds 5f and 5t exhibited markedly improved antiviral efficacy compared to the reference drug, acyclovir. The antioxidant capacity was also notable, with compound 5b showing exceptional radical scavenging potential. Docking studies were conducted to better understand their molecular interactions with the target protein. The findings demonstrated that these molecules could potentially inhibit HSV-1, targeting a key enzyme involved in viral replication. Additionally, in silico analyses were performed to assess drug-likeness, absorption, distribution, metabolism, and excretion characteristics, and metabolic stability, which may aid in the optimization of future lead compounds. Although the experimental methods were accurately implemented, minor variations associated with human error, such as differences in timing during compound administration, measurements, and other experimental procedures, may have occurred. These possible variations, however, are unlikely to significantly affect the observed trends. Ultimately, the study emphasizes these new triazole–pyrazine hybrids as potential lead compounds for the development of potent anti-HSV–1 and possibly antibacterial agents, warranting further pharmacological and clinical investigation.
Cancer remains a major clinical challenge that requires adaptive strategies. This review synthesizes principal therapeutic modalities, with emphasis on drug resistance, how drugs are ordered, and dealing with side effects while keeping the patient in mind. Evidence from pivotal trials and real-world practice demonstrates that resistance affects the treatments selected. Side effects and patient situations are considered to find the right balance between the treatment’s effectiveness and the patient’s quality of life. This review also examines the sequencing of chemotherapy with immune checkpoint blockade, as well as new approaches such as messenger RNA vaccines and proteolysis-targeting chimeras. Cross-cutting issues-including treatment standards, ethical considerations, and economic barriers-are discussed to help shape future cancer care delivery.
The high mutation frequency of the SARS-CoV-2 spike (S) gene undermines the reliability of S-based diagnostics. Identifying conserved protein epitopes that remain stable across SARS-CoV-2 variants is paramount in resource-limited settings. This study aims to identify conserved gene regions of SARS-CoV-2 using whole-genome sequencing and immunoinformatics to support the development of monoclonal antibody-based rapid diagnostics. SARS-CoV-2 positive samples (Ct ≤ 30) collected in Ethiopia (June–August 2022) from a retrospective study (n = 70) were sequenced using Illumina NextSeq-550. Conserved regions were identified via Multiple Alignment using Fast Fourier Transform, entropy plots, and mutation profiling. B-cell epitopes were predicted and assessed for antigenicity and cross-reactivity. Structural modeling was conducted using AlphaFold and visualization tools. High-quality whole-genome sequencing of 63 SARS-CoV-2 samples revealed conserved regions in the nucleocapsid gene across major variants. Three surface-exposed, antigenic, and non-allergenic B-cell epitopes were identified with low cross-reactivity to common human coronaviruses. Structural modeling and docking confirmed their accessibility and strong antibody binding, supporting their potential for robust diagnostic applications. In conclusion, conserved N protein epitopes identified in this study are promising targets for developing robust, variant-resistant rapid diagnostic tools.
Small ruminant lentiviruses are common viral pathogens affecting livestock, primarily sheep and goats, and are responsible for chronic and fatal diseases such as Maedi- Visna and caprine arthritis encephalitis. These infections compromise livestock productivity. Developing a safe and effective vaccine that provides broad protection across host species remains a major challenge. Consequently, we employed different bioinformatics tools to design a novel multi-epitope vaccine construct based on the envelope gene of the causative lentiviruses. The secondary and tertiary structures of the construct were predicted and subsequently refined. The stability and binding affinity of the vaccine construct were evaluated using advanced computational approaches, including molecular docking and molecular dynamics simulation. Also, the immunogenic potential was assessed through immune simulation studies, followed by codon optimization and in silico cloning. However, in vivo studies are required in the near future to confirm the vaccine construct’s efficacy and immunogenicity.
Viruses, as a population of subcellular entities of genetic material in a package, are at least an order of magnitude as numerous as that of their cellular hosts, on which they depend. While the particulars of the emergence of the ancestors of viruses are unknown, the evolutionary histories of their genes are possible by the evolutionary methods of gene sequence comparison and phylogenetic reconstruction. These studies depend on nucleotide or protein sequence data and a reference to the underlying process of genetic replication, which is a cause of taxon-specific differences in the rates of genetic mutation and correction of replication errors. Viral types also do not easily fit within the confines of traditional typologies, such as the use of a host preference for a biological marker of their taxonomic assignments. Instead, their population processes are dynamic and vary across taxa, which are causes of genetic change and new viral lineages. Since a naive deterministic model of evolution is not supported in the corpus of modern science, it is instead an ideal to infer knowledge of viral origins by models based on the stochastic processes of molecular evolution. These approaches are the basis for validating and building knowledge on virus evolution that leads to confidence and robustness in scientific findings (a requisite to the formation of a scientific belief).
The functions of magnesium (Mg) and angiotensin-converting enzyme 2 (ACE2) in lowering blood pressure are well known; however, their roles in long COVID (LC) remain unclear. This review proposes a hypothetical model that mechanistically links symptoms of LC to: (i) deficiencies in essential ACE2-dependent neutral amino acids, including tryptophan and methionine; (ii) altered Mg-dependent one-carbon metabolism; (iii) altered Mg-dependent autophagy; and (iv) altered Mg-dependent mechanistic target of rapamycin (mTOR) signaling, potentially modulated by rapamycin. Mg and vitamin D deficiency are linked to LC. All forms of vitamin D, including its cutaneous precursor, are Mg-dependent. Accordingly, Mg is proposed as an essential factor in the prevention and/or attenuation of LC. The SARS-CoV-2 virus targets ACE2-expressing cells, leading to the downregulation of ACE2 function. ACE2 and sodium-dependent neutral amino acid transporter are required for the absorption of tryptophan, methionine, and branched-chain amino acids, all of which are low in LC. Loss of ACE2 negatively impacts the Mg-dependent serotonin pathway, the Mg-dependent indole pathway, and the methionine-dependent one-carbon metabolism. Autophagy and mTOR kinase are Mg-dependent. Additionally, individuals carrying the methylenetetrahydrofolate reductase 677T allele-which is prevalent in many populations-may exhibit further impairment in one-carbon metabolism. Gut dysbiosis, present in almost 75% of long haulers, may enable Candida overgrowth. Candidalysin has been shown to upregulate mTOR and inhibit autophagy, similar to mechanisms employed by several viruses, including SARS-CoV-2, and may contribute to chronic fatigue. Although numerous linkages are outlined, this mechanistic model is hypothetical, and causal relationships require validation through clinical studies.
Cymbopogon citratus (lemongrass) is a widely utilized medicinal and aromatic plant with a long history of traditional applications across Asia, Africa, and South America. In recent decades, scientific attention has increasingly focused on elucidating its phytochemical composition and validating its therapeutic properties through experimental and molecular studies. The present review critically synthesizes current evidence on the phytochemical constituents of C. citratus and their antimicrobial, antioxidant, and cytoprotective effects, with particular emphasis on underlying biological mechanisms and emerging biomedical relevance. Major bioactive compounds, including citral, flavonoids, phenolic acids, terpenoids, and essential oils, are discussed in relation to their roles in inhibiting pathogenic microorganisms, neutralizing oxidative stress, and maintaining cellular integrity. The review further highlights mechanistic pathways such as membrane disruption, enzyme inhibition, reactive oxygen species modulation, mitochondrial protection, and anti-inflammatory signaling. Recent advances in nanotechnology-based formulations and functional therapeutic applications are also examined. Collectively, the evidence positions C. citratus as a promising natural source for the development of antimicrobial and cytoprotective agents, supporting further translational and clinical investigations. This review synthesizes evidence from experimental, mechanistic, and translational studies published over the last two decades.
Saccharomyces boulardii is a well-established probiotic yeast with documented clinical benefits for gastrointestinal health. This review highlights the key biotherapeutic mechanisms underlying its protective effects, with particular emphasis on its bioactive metabolites, including specialized enzymes, polyamines, organic acids, and vitamins. These postbiotic factors contribute to epithelial barrier reinforcement, immune modulation, and pathogen exclusion, thereby promoting intestinal homeostasis. In addition, S. boulardii supports microbial equilibrium through colonization resistance and regulation of inflammatory signaling pathways, including nuclear factor kappa-light-chain-enhancer of activated B cells. Clinical evidence demonstrates its efficacy in the prevention and management of antibiotic-associated diarrhea, inflammatory bowel disease, and irritable bowel syndrome. Safety considerations are also addressed, noting its biological distinction from Saccharomyces cerevisiae, particularly its inability to undergo hyphal transformation. Owing to its resilience against gastric acidity, bile salts, and concomitant antibiotic therapy, S. boulardii represents a valuable adjunct in contemporary gastrointestinal therapeutics and a promising platform for functional and translational applications.
Lung transplantation (LTx) is the definitive therapeutic option for patients with end-stage lung disease. Improving long-term survival remains a central focus of clinical research in LTx, particularly because post-transplant infection, acute and chronic rejection, and chronic lung allograft dysfunction continue to limit graft survival. However, the prognosis of LTx recipients depends not only on surgical technique but also on pulmonary microbial ecology and immunosuppressive strategies. In recent years, advances in LTx research have increased interest in the post‑LTx pulmonary microbial ecosystem, especially its dynamic remodeling and multifaceted interactions with the host immune system, which play critical roles in infection, rejection, and long-term prognosis. Previous studies have shown that LTx-induced changes in microbial community structure affect the stability of the pulmonary environment and are closely associated with immune rejection, thereby representing key determinants of graft survival. Mechanistically, microbial dysbiosis may influence innate immune activation, macrophage polarization, regulatory T cells and T helper 17 cells balance, microbial metabolites, and gut–lung axis-mediated systemic inflammation. However, the underlying mechanisms of microbial ecology and immune regulation remain unclear, hindering the development of precision therapies and personalized management strategies. This review summarizes post‑LTx pulmonary microbial community dynamics, immune responses, and bidirectional regulatory mechanisms between the immune system and microbiota, and discusses their impact on graft function, with implications for immune management and microbial ecological regulation strategies. Recent advances in multi-omics analysis, microbiome-related biomarkers, artificial intelligence-assisted analysis, non-invasive monitoring, and methodological standardization may further support precision management in LTx recipients.
Honey from citrus limon is of interest for wound healing due to its antimicrobial, antioxidant, and immunomodulatory properties. This in vitro study investigates whether citrus lemon honey (CLH) can modulate key cellular and biochemical processes involved in wound healing, in comparison with Manuka honey. Antioxidant, anti-inflammatory, and antibacterial activities were evaluated alongside keratinocyte (HaCaT) proliferation and migration assays. Physicochemical analysis showed high water-soluble protein content (480.9 ± 28.4 mg equivalent [Eq] bovine serum albumin/100 g), acidic pH (3.4 ± 0.02), low moisture (19.5%), and moderate electrical conductivity (41.6 ± 2.61 μS/cm). In addition, CLH exhibited notable phenolic (313.6 ± 0.6 mg Eq gallic acid/100 g) and flavonoid contents (6.9 ± 2.6 mg Eq quercetin/100 g), accompanied by strong antioxidant activity (total antioxidant capacity: 3.5 ± 0.05 g Eq ascorbic acid/100 g). CLH demonstrated antibacterial activity against both Gram-positive and Gram-negative bacteria (minimum inhibitory concentrations of 0.8–3.1 w/w%), including clinically relevant wound-associated pathogens, highlighting its potential to reduce microbial burden and prevent infection in wound environments. Furthermore, CLH modulated nitric oxide production in lipopolysaccharide-activated THP-1 macrophages. Functionally, CLH promoted keratinocyte viability and migration in a concentration-dependent manner, with an approximately 20% increase in cell viability at 1–2 mg/mL and a 35% enhancement in migration, without cytotoxicity. These effects were comparable in trend, though less pronounced, to those observed with Manuka honey. Taken together, the combined antibacterial, anti-inflammatory, and pro-regenerative effects suggest that CLH may support wound healing by enhancing tissue repair and limiting infection. From a host–microbe interaction perspective, the antibacterial and immunomodulatory effects of CLH suggest a coordinated role in wound healing, where reduced microbial burden and controlled regulation of inflammation may act synergistically to support tissue repair and restore skin integrity. However, further in vivo and clinical studies are required to confirm its therapeutic relevance.
Antimicrobial resistance (AMR) poses an escalating threat to global health by compromising the effectiveness of conventional antibiotics and increasing the risk of treatment failure for common infections. As the development of new antibiotics lags behind the rapid emergence of resistant pathogens, alternative strategies are urgently needed to sustain effective infection management. Vaccines and non- antibiotic therapeutics represent complementary approaches that can reduce reliance on conventional antimicrobials while limiting the selective pressures that drive resistance. While vaccinations prevent infections, reduce pathogen transmission, and decrease antibiotic consumption at both individual and population levels, precision therapeutics, in parallel, enable targeted treatment of resistant infections while preserving host microbial ecology. This review synthesizes current evidence on the role of vaccines as underutilized tools for AMR mitigation and examines emerging non-antibiotic therapeutic strategies with translational and clinical potential. Beyond individual modalities, we propose an integrated framework that combines prevention, precision interventions, stewardship, and surveillance to enhance AMR control. Key considerations include research priorities, regulatory pathways, implementation challenges, and equitable access across diverse healthcare settings. By shifting from a predominantly antibiotic-centered approach toward prevention and targeted biologic interventions, these strategies offer a sustainable pathway to reduce the burden of AMR and preserve the effectiveness of existing therapies.
Crustaceans lack immunoglobulins, and their humoral immunity relies on immune factors present in the hemolymph. A native hemolymph protein with a molecular mass of approximately 120 kDa was found to bind the swimming crab (Portunus trituberculatus) reovirus (SCRV) via virus overlay protein binding assays. This protein was identified as cryptocyanin using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis and sequence alignment. The interaction between SCRV and cryptocyanin was confirmed by coimmunoprecipitation. In the antiviral assays in vivo, cryptocyanin enhanced the survival of P. trituberculatus. Our findings showed for the first time that cryptocyanin can seize viruses, suggesting that cryptocyanin may participate in anti‑infective immunity. This study identifies cryptocyanin as a novel and essential component of the invertebrate innate immune system and provides a theoretical basis for elucidating its function in antiviral defense mechanisms.
This study evaluated the effects of different Arachis hypogaea dietary preparations on parasite load, hematological indices, and physiological responses in Plasmodium berghei-infected mice. Albino mice (n = 45) were randomly assigned to five groups: normal control, infected untreated control, roasted groundnut, boiled groundnut, and a combination of roasted and boiled groundnut diets. Data were analyzed using one-way analysis of variance; p < 0.05 indicated statistical significance. Infection resulted in a high parasite load in the untreated group, with no significant difference compared to the boiled and combined diet groups. However, the roasted groundnut group showed a reduction in parasite load and relatively higher chemosuppressive activity, although differences were not statistically significant. White blood cell counts increased significantly following infection, and dietary treatments did not restore normal levels. Similarly, red blood cell counts and packed cell volume were significantly reduced in infected mice. The roasted groundnut diet moderately improved packed cell volume compared to other treatments, but did not restore it to normal levels. Weight loss was most pronounced in untreated mice, while roasted groundnut intake showed slight mitigation. No significant effects on temperature regulation were observed. Overall, A. hypogaea diets did not significantly reduce parasitemia or improve hematological parameters, indicating limited therapeutic value for malaria management.
Primary healthcare (PHC) workers are central to immunization delivery, yet knowledge and practice gaps continue to undermine the control of vaccine-preventable diseases across sub-Saharan Africa. Nigeria carries the heaviest zero-dose burden on the continent, with over 2.1 million children remaining unvaccinated annually. This study assessed immunization knowledge, attitudes, and practices among PHC workers in rural Kogi local government area (LGA) and urban Lokoja LGA, and identified predictors of immunization practice. A comparative cross-sectional survey enrolled 130 PHC workers through stratified random sampling (Kogi: n = 68; Lokoja: n = 62), using a structured questionnaire and analyzing data with independent-samples t-tests, χ2 tests, and linear and logistic regression in SPSS (α = 0.05). Overall, 78.0% of participants demonstrated good knowledge (mean = 7.70 ± 1.55); however, gaps persisted. Only 30.8% correctly identified that freezing inactivates diphtheria-tetanus-pertussis/Hepatitis B/Pentavalent vaccines, and fewer than half (46.9%) recognized that live vaccines are safe for mildly ill children. Knowledge significantly predicted practice (β = 0.192, p = 0.028), though it accounted for only 3.7% of the variance in practice. A multivariable model explained 15.5% of variance, with knowledge (p = 0.028) and rural location (β = 0.198, p = 0.034) as significant independent predictors. Rural workers reported better immunization practices than their urban counterparts (4.20 vs. 3.67; p = 0.034) despite comparable knowledge levels, suggesting that contextual factors, including supervision intensity and workload distribution, shape performance beyond individual knowledge. Prior training was the strongest predictor of good knowledge (odds ratio = 10.52, p = 0.001). These findings show that addressing Nigeria’s immunization gap requires more than training alone; sustained improvements in staffing, supervisory systems, and cold chain infrastructure are equally essential.