Frontiers in Cellular and Infection Microbiology最新文献

Skin wound infections are common and clinically challenging. Conventional antibiotic therapies are increasingly ineffective because of escalating bacterial resistance, highlighting the urgent need for alternative treatment strategies. Antibacterial hydrogels, multifunctional polymeric materials that integrate moisturizing, drug delivery, controlled release, and wound-healing properties, have emerged as highly promising candidates for managing infected wounds. Based on their underlying antimicrobial mechanisms, these systems can be broadly classified into three main categories: chemical, physical, and biological antibacterial hydrogels, which achieve bactericidal efficacy through drug release, physical disruption, or modulation of the host microenvironment and immune responses, respectively. Of tremendous significance is the advent of stimuli-responsive intelligent hydrogels, which provides new opportunities for achieving precise and efficient antibacterial therapy. This review systematically summarizes the material selection, design strategies, and representative advances in antibacterial hydrogels, with particular emphasis on their core mechanisms, strengths, and limitations, aiming to offer theoretical foundations and research perspectives for the rational optimization and clinical translation of next-generation antibacterial hydrogels.

Nontargeted metagenomic surveillance of the poultry enteric virome reveals underrecognized threats to poultry health and productivity in intensive production systems. In South Asia, avian rotavirus A (AvRV-A) and avian orthoreovirus (ARV) are frequently detected in broilers by conventional diagnostics, whereas chicken megrivirus genotype C (ChMeV-C) is often identified through metagenomic surveillance. Often present in both clinical disease and coinfections, these viruses may impair gut function, immune responses, and growth performance, yet their genomic diversity and evolutionary dynamics in poultry remain poorly characterized. Here, we report complete genomes of AvRV-A, ARV, and ChMeV-C strains co-detected via nontargeted metagenomic next-generation sequencing (ntNGS) in a pooled cloacal sample comprising 150 commercial broiler chickens (19 and 33 days old) collected from three commercial farms in Kamrup Rural District, Assam, Northeast India. Despite routine vaccination, all three flocks experienced > 10% mortality, poor weight gain, and postmortem lesions including pale kidneys and hepatomegaly. Phylogenetic analyses revealed segmental clustering in ARV and AvRV-A consistent with reassortment-driven divergence, though not supported by detectable recombination, while ChMeV-C clustered within a distinct C1 sublineage, suggesting intercontinental lineage connectivity and highlighting the need to expand regional genomic baseline data. We also identified nonsynonymous single nucleotide polymorphisms in several key viral proteins, including RNA-dependent RNA polymerases (VP1 of AvRV-A, λB of ARV, and 3D of ChMeV-C), capsid proteins (VP2 and VP7 of AvRV-A, λA and σB of ARV, and VP0 and VP1 of ChMeV-C), and replication-associated nonstructural proteins. These findings expand the genomic baseline for poultry enteric viruses in South Asia, reveal novel polymorphic signatures, and underscore the value of ntNGS-based metagenomic surveillance in virus detection, diversity monitoring, and informing vaccine and biosecurity strategies.

The prevalence of mupirocin resistance in MRSA severely limits therapeutic options for skin and soft tissue infections. This study aimed to evaluate the potential synergistic activity between mupirocin and protocatechuic acid ethyl ester (EDHB) through in vitro and in vivo investigations. Clinical S. aureus isolates were characterized for antibiotic resistance profiles and molecular features via antimicrobial susceptibility testing, MLST, and spa typing. For MRSA isolates, checkerboard and time-kill assays were performed to assess in vitro synergy. The potential interference of EDHB with bacterial membrane integrity and efflux pumps was investigated using propidium iodide and ethidium bromide, respectively. The disk diffusion method was applied to test the retained antimicrobial activity of mupirocin and EDHB in ointment formulations. A murine dermal wound model was established to evaluate in vivo efficacy by topical application of mupirocin and EDHB, alone or in combination, on infected wounds. EDHB alone exhibited limited activity but synergistically reduced mupirocin MICs by 4-8-fold in most strains. Checkerboard analysis revealed synergistic or partial synergistic interactions against MRSA. Time-kill curves further indicated that combining these two drugs can effectively inhibit the planktonic S. aureus. EDHB rapidly disrupts cytoplasmic membrane integrity via concentration-dependent propidium iodide influx, independent of norA/mepA efflux pump modulation. The enhanced antibacterial activity of mupirocin and EDHB was sustained in ointment formulations, resulting in superior therapeutic outcomes with combination therapy compared to monotherapy. EDHB acts as a membrane-disrupting adjuvant that synergizes with mupirocin against MuR-MRSA, offering a promising strategy to combat recalcitrant S. aureus infections through localized combination therapy.

The oral-gut axis represents a critical bidirectional pathway linking oral microbiota to systemic health. Dysbiosis of the oral microbiome, driven by pathogens like Porphyromonas gingivalis, Fusobacterium nucleatum, Streptococcus species, and Helicobacter pylori, disrupts gut ecology via direct translocation, metabolite signaling (e.g., TMAO, SCFAs), and immune crosstalk (e.g., Th17). This leads to gut barrier dysfunction, systemic inflammation, and metabolic disturbances, contributing to diverse diseases beyond the oral cavity. Evidence supports causal links with conditions including rheumatoid arthritis, cardiovascular diseases, neurodegenerative disorders, metabolic syndrome, and gastrointestinal cancers. Emerging diagnostic tools exploit these oral pathogens as biomarkers for non-invasive disease detection. Therapeutic strategies, such as probiotics, dietary interventions, and periodontal therapy, target this axis to restore microbial homeostasis and ameliorate systemic inflammation. Future research must focus on longitudinal human studies and multi-omics approaches to elucidate mechanistic details and develop effective clinical interventions for preventing and managing systemic diseases linked to oral-gut microbial dysbiosis.

Objective: To characterize the systemic effects of high-fat diet (HFD)-induced obesity across different ages, explore the microbiota-related obesity endotype using 16S rRNA sequencing, and identify key microbial genera as candidate markers for longitudinal monitoring and future interventional validation.

Materials and methods: Male C57BL/6J mice were randomly assigned to a standard chow diet (SCD) or HFD group, maintained until 4, 12 and 18 months of age as the young, middle-aged and old groups, respectively, at which time animals were euthanized. Systemic effects were evaluated by measuring body weight, Lee's index, glucose-lipid metabolism, liver function, and blood oxygen levels, coupled with behavioral tests for mood and cognitive performance. Blood samples were collected to quantify LPS and Aβ1-42 levels using ELISA. Oral and fecal samples were collected for 16S rRNA sequencing to analyze microbiota diversity and community structure. Differential genera were identified by LEfSe, and those consistently altered in both oral and gut samples were operationally designated as marker genera. Targeted metabolomics was performed to analyze short-chain fatty acids (SCFAs). Correlations were evaluated using Spearman analysis.

Results: Compared with SCD, HFD mice showed systemic alterations across all age groups, including progressive obesity, elevated blood lipids and liver enzymes, accompanied by reduced blood oxygen, increased Aβ1-42 and LPS levels, increased anxiety-/depression-like behaviors, and impaired spatial memory. HFD significantly remodeled the alpha/beta-diversity and community structure of oral and gut microbiota, inducing stable enrichment of Romboutsia_B and depletion of beneficial genera (Bifidobacterium, Akkermansia, and Muribaculum). The abundance of Romboutsia_B positively correlated with obesity, blood lipids, liver enzyme levels, hypoxia, and inflammatory markers, but negatively correlated with multiple cognitive-behavioral parameters. Functional prediction and SCFA further profiling indicated that HFD enhanced lipid metabolism and environmental adaptation pathways, while reducing polysaccharide degradation and vitamin metabolism.

Conclusions: Long-term HFD is associated with systemic remodeling of the oral-gut-liver-brain axis across ages. Romboutsia_B, a pro-inflammatory-associated genus stably enriched in the oral and gut across all age groups, holds potential as a noninvasive microbial biomarker and candidate target for future intervention studies for obesity and its liver-brain comorbidities.

Coccidiosis, caused by Eimeria parasites, is a major threat to global poultry production, and increasing restrictions on conventional anticoccidial drugs highlight the need for safer, more sustainable alternatives. Progress has been hindered by the lack of rapid, sensitive, and animal-sparing in vitro assays for quantifying parasite replication and drug efficacy. This study reports the development of a novel bioluminescent platform for anticoccidial screening based on a genetically modified Eimeria tenella line expressing NanoLuc luciferase (EtNluc). Parasite-associated bioluminescence enabled rapid and quantitative monitoring of intracellular development, allowing the tracking of different replication phases through schizont formation and merozoite release. Time course analysis showed minimal changes in relative light units (RLU) between 2 and 24 hours post infection (hpi), followed by a marked increase between 24 and 72 hpi, consistent with parasite replication. Among the tested multiplicities of infection (MOI), 4:1 exhibited the fastest growth, described by a linear model (slope = 2908 RLU/h, R² = 0.84). A same-well repeated-measure analysis (2 and 72 hpi) confirmed the dose-dependent replication, with mean slopes of 2052.85, 765.07 and 523.63 RLU/h, respectively, supporting the selection of the MOI 4:1 for anticoccidial screening. These experimental conditions were used to evaluate the anticoccidial efficacy of commercial anticoccidial drugs (salinomycin and robenidine) and natural compounds (thyme and oregano essential oils, thymol, and carvacrol) under two experimental designs: short pre-incubation of sporozoites, and continuous exposure throughout intracellular development. Pre-incubation with commercial anticoccidials reduced invasion approximately to 65% for salinomycin and 44% for robenidine, whereas the essential oils and their bioactive constituents inhibited invasion by 30-55%, and reduced the replication slope to 33-60% of control values. Continuous exposure significantly impaired intracellular development for all treatments, reducing replication to 10-30% of controls, providing additional evidence that plant-derived compounds can complement commercial anticoccidials for integrated strategy for coccidiosis control in chickens. Overall, the EtNluc bioluminescent system provided a rapid, sensitive, and scalable method for quantifying E. tenella growth, suitable for in vitro anticoccidial screening, supporting the characterization of novel anticoccidial while reducing reliance on animal experimentation.

[This corrects the article DOI: 10.3389/fcimb.2025.1612198.].

Fungal diseases represent a growing yet under-recognized global health threat, with mortality comparable to major infectious diseases but a disproportionately weak therapeutic pipeline. This review examines the antifungal innovation gap as a systemic phenomenon shaped by intertwined scientific, economic, and societal constraints. While multidrug-resistant pathogens underscore the urgent need for new antifungal agents, progress is hindered by fungal-human cellular similarity, high development costs, limited commercial incentives, and toxicity concerns. Agricultural fungicide practices that drive resistance and intellectual-property regimes that restrict affordability and generic entry further complicate this landscape. These scientific and economic barriers coexist with profound inequities in global access to existing antifungals, revealing a persistent gap between therapeutic availability and public health needs. The resulting public-health consequences include delayed treatment, reliance on suboptimal therapies, and widening disparities in outcomes across low-resource settings. This review proposes that antifungal agents should be conceptualized as global public goods and that non-profit development models offer a promising pathway to overcome current bottlenecks. An integrated perspective across clinical, agricultural, regulatory, and public-health domains underscores the need for coordinated strategies to restore innovation, ensure equitable access, and strengthen global preparedness against fungal diseases.

Background: Sepsis continues to be a life-threatening complication following ureteroscopic lithotripsy (URSL). Available clinical prediction tools tend to be inadequate in their capacity to depict the underlying pathophysiology of sepsis-systemic immune-inflammatory imbalance. It is particularly difficult in patients who lack obvious preoperative microbiological findings. The study aims to evaluate the new Systemic Immune-Inflammatory Complex Index (SIICI) as well as other indices such as (SII, SIRI, PIV) in predicting post-URSL sepsis.

Methods: We performed a single-center retrospective study of 803 patients who underwent URSL. Multivariate logistic regression was used to create a clinical baseline model. To assess the incremental predictive value, each inflammatory index was added separately to the baseline model. The model performance was compared using the area under the ROC curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), likelihood ratio test (LRT) and decision curve analysis (DCA).

Results: The "Base + SIICI" model was found to be the most effective among the four indices. It had the highest degree of discrimination (AUC = 0.863, 95% CI: 0.819-0.908), which is a considerable improvement over the baseline model (AUC = 0.807, p<0.001). There were meaningful improvements in reclassification (NRI = 0.133, p=0.001) and discrimination (IDI = 0.058, p=0.002), a significant likelihood ratio test (p<0.001) backed up these findings. The decision curve analysis confirmed that higher net clinical benefit was found at a larger variety of probability thresholds. Notably, the model performed well in individuals with negative preoperative urine cultures (AUC = 0.850). A visual nomogram was developed and validated based on this model, showing good calibration and a bootstrap-corrected AUC of 0.849. An online calculator was also created to facilitate clinical application.

Conclusion: SIICI is a new index that offers high incremental value in predicting sepsis after URSL compared to traditional indices like SII, SIRI and PIV. Nomogram based on SIICI presents a strong and useful instrument of early stratification of risks of development and can assist in making proactive clinical decisions, particularly where standard infection indicators cannot be used.

The rising burden of neglected infectious diseases and the accelerating spread of antimicrobial resistance (AMR) demand rapid, accurate, and decentralized diagnostic solutions. Point-of-care (POC) molecular diagnostics enable early diagnosis and resistance profiling during the clinical encounter, without reliance on centralized laboratories, which is particularly important in low-resource settings. Molecular POC technologies are being developed around the following advances: isothermal nucleic acid amplification technologies, rapid polymerase chain reaction (PCR), CRISPR-based diagnostic detection technologies, nanomaterials-enabled biosensors, and microfluidic platforms for sample-to-results with near laboratory-quality accuracy within clinically relevant timeframes (typically < 30 minutes). The combination of artificial intelligence (AI) and cloud-based digital health systems supports the automated interpretation and provision of real-time surveillance and antimicrobial stewardship. Next-generation molecular POC platforms provide higher sensitivity and mechanistic insights into drug-resistance in TB, malaria, and bacterial infections. Barriers include clinical validation, cost, scalability, and equitable access. The convergence of molecular diagnostics, nanotechnology and AI-powered analytics leads to future-oriented, transformative opportunities in precision therapy areas, AMR surveillance and infectious disease preparedness.