npj Biofilms and Microbiomes最新文献

With the increase in the placement of prosthetic joints and other hardware in the body, associated infections have risen. These infections are complicated to treat due to the underlying bacteria generating matrices that resist clearance by immune system effectors or antibiotics. These matrices, biofilms, have two primary ways of being eradicated: either by physical removal during surgery or by killing the underlying bacteria, usually with antibiotics. The viruses that kill bacteria, bacteriophages, are readily capable of entering biofilms and eradicating the bacteria therein. Therefore, bacteriophages have therapeutic potential as a supplement to antibiotics for the treatment of prosthetic joint infections. In this investigation, we generate a mathematical and computer-simulation model to explore the contributions of the innate immune system with antibiotics, bacteriophage, and the joint action to control biofilm-associated infections. Our results question the proposition that bacteriophages are an effective addition in the treatment of prosthetic joint infections.

Oral microorganisms contribute to the progression of oral squamous cell carcinoma (OSCC), and the gut microbiome may also influence OSCC by modulating systemic immunity. This study investigated oral and gut microbial changes in a 4-nitroquinoline N-oxide (4-NQO)-induced OSCC mouse model. After 16 weeks of 4-NQO exposure, significant alterations were observed in the beta diversity of both oral and gut microbiomes. Notably, the relative abundance of Lactococcus increased, especially in oral microbiomes, from week 6 to 16, followed by a decline at week 22, suggesting a 4-NQO-induced niche favorable to its proliferation. Absolute quantification revealed a 4-NQO-induced increase in total bacterial load in the oral cavity, accompanied by elevated absolute abundance of Lactococcus. Unexpectedly, oral administration of Lactococcus strains isolated from 4-NQO-treated mice mildly alleviated inflammation. In vitro, lysates from these strains exhibited protein-dependent cytotoxicity against murine OSCC cells. These results suggest that Lactococcus strains may exert protective effects during OSCC progression.

Treatment options for Staphylococcus aureus infections are increasingly limited, particularly in livestock, where S. aureus causes mastitis requiring prolonged antibiotic therapy. This study engineered Phage Inducible Chromosomal Islands (ePICIs) to deliver CRISPR-Cas9 modules targeting small RNA genes. ePICIs exhibit bactericidal activity without chromosomal integration, an expanded host range compared to their parental phages, and biofilm-dependent efficacy influenced by the extracellular matrix composition. Biofilms mediated by the Bap protein strongly protect bacteria from ePICIs, whereas PIA/PNAG-based biofilms do not. Despite Bap-mediated protection in vitro, ePICIs achieved bactericidal effects comparable to vancomycin in a mouse mastitis model caused by Bap-producing strains. These findings reveal key factors affecting phage-delivered CRISPR-Cas efficacy and highlight that antibiofilm therapies should not be dismissed based solely on in vitro performance. Non-replicative ePICIs thus represent a promising alternative for treating localized infections such as mastitis.

It has become increasingly appreciated that gut microbes influence host stress hormone responses through direct and indirect mechanisms. These relationships may have broad implications on hormone bioavailability, receptor signaling, and stress resilience. In this review, we summarize current evidence for microbe-stress factor interactions and their consequences for host physiology. We further examine how microbiota-stress crosstalk may contribute to inflammatory bowel disease, highlighting emerging mechanisms and potential microbiota-targeted therapies.

The interplay between nutrient availability and arbuscular mycorrhizal fungi (AMF) symbiosis during plant growth exhibits intricate complexity. In this study, we employ integrated physiological, transcriptomic, proteomic, and metabolomic analyses to investigate how sugarcane differentially adapts to nitrogen (N) fertilization and AMF colonization. Under nitrogen stress conditions, AMF colonization significantly enhances sugarcane growth, increasing plant height, stem diameter, and biomass while stimulating root exudation and rhizospheric nutrient mobilization-particularly available N, phosphorus (P), and potassium (K). Multi-omics analyses reveal that AMF induces nitrogen-dependent metabolic reprogramming in sugarcane roots, activating pathways such as carbohydrate and lipid metabolic pathways while suppressing butanoate and ascorbate metabolism. Weighted gene co-expression network analysis (WGCNA) identifies key root modules strongly correlated with soil N, P, and K availability, indicating AMF-mediated coordination of nutrient acquisition strategies. Field trials demonstrate that AMF boost sugarcane yield under nitrogen stress by enhancing root elongation and carbon partitioning for sucrose accumulation. Temporal integration of transcriptomic and metabolomic data highlights flavonoid biosynthesis as a persistently activated pathway across growth stages, potentially facilitating AMF symbiosis and stress resilience. Our findings elucidate how sugarcane optimizes AMF-mediated nutrient acquisition under nitrogen stress through root transcriptional and metabolic adjustments, providing insights for sustainable crop nutrient management.

Alveolar echinococcosis (AE), a chronic parasitic disease caused by Echinococcus multilocularis (E. multilocularis), remains poorly characterized with respect to central nervous system (CNS) involvement, and its long-term effects on mental health have not been systematically investigated. In this study, we established a BALB/c mouse model of chronic E. multilocularis infection and applied an integrative framework combining behavioral assessments, histomorphological analyses (hematoxylin-eosin staining, Nissl staining, and transmission electron microscopy), cytometric bead array (CBA), and multi-omics approaches (16S rRNA sequencing, metagenomics, and untargeted metabolomics) to investigate infection-induced neuroimmune-gut microbiota interactions. Chronically infected mice exhibited pronounced depression-like behavioral phenotypes, accompanied by hippocampal neuronal nuclear membrane atrophy and disrupted microglial homeostasis. Both peripheral and central inflammatory profiling revealed elevated levels of pro-inflammatory mediators, particularly IL-6 and MCP-1, suggesting coordinated systemic immune activation and neuroimmune alterations. Notably, fecal microbiota transplantation (FMT) from infected donors was sufficient to induce depression-like behaviors in recipient mice, supporting a contributory role of infection-associated gut microbiota alterations in behavioral abnormalities. Integrated multi-omics analyses further revealed a marked reduction in Lactobacillus abundance in infected mice, which was positively correlated with decreased levels of key metabolites within the tryptophan/5-hydroxytryptamine (5-HT) metabolic pathway. Collectively, these findings suggest that chronic E. multilocularis infection may be associated with depression-like behaviors through gut microbiota dysbiosis and related metabolic perturbations. This study provides initial insights into the potential mechanisms underlying neuropsychiatric complications in AE and proposes a conceptual framework for future investigations into early intervention and microbiota-targeted therapeutic strategies.

The coexistence and horizontal transfer of antibiotic resistance genes (ARGs) and virulence factor genes (VFGs) carried by urban wildlife represent an emerging form of biological pollution, constituting a significant threat to public health. We employed meta-omic approaches to evaluate the effects of host traits (sex, age, etc.), environmental factors (including geographical location and time), and diet (including food composition and antibiotic residues) on the bacterial, ARG, and VFG profiles of Vespertilio sinensis, an urban-dwelling bat. Our results demonstrate that the feces of V. sinensis harbor diverse ARGs and VFGs, but their genomic evidence for horizontal mobility in bacterial communities is limited. Notably, environmental changes over time and across geographical locations are associated with the ARG and VFG profiles, potentially due to the influence of pollutants in specific habitats. Dietary factors are associated with their dynamics through the microbiome, with antibiotic residues exerting selective pressure on ARG profiles. No significant impacts of sex, age, body size, and reproductive status on the gut microbiota, resistome, or virulome were observed. This study provides valuable insights into the ecological drivers of the gut microbiome, resistome, and virulome in bats, thereby contributing to our understanding of the public health risks associated with urban wildlife.

Major Depressive Disorder (MDD) affects around 20% of people globally and is often comorbid with anxiety. This study investigates prucalopride, a serotonin type 4 receptor (5-HT₄R) agonist approved for constipation, as a fast-acting anxiolytic/antidepressant using a mouse model of stress, based on corticosterone (CORT) administration. Behavioral effects of prucalopride (0.5 and 1.5 mg/kg/day) were compared to fluoxetine, a common SSRI, over 7 (subchronic) and 28 (chronic) days. Prucalopride showed faster and more significant improvements in emotionality scores than fluoxetine, reversing CORT-induced behavioral changes within 7 days. Gut microbiota analysis revealed CORT-induced changes at the subchronic timepoint. While chronic prucalopride did not alter microbial alpha diversity, it significantly shifted microbial composition (beta-diversity). Notably, prucalopride restored levels of the genus Ruminococcus, which were depleted by CORT. Our findings highlight prucalopride's rapid anxiolytic and antidepressant-like effects and its impact on gut microbiota, supporting the potential of 5-HT₄R-targeting molecules as therapeutic options for psychiatric disorders.

Exopolysaccharides (EPS) are critical components of the biofilm matrix, and ppGpp has been demonstrated to positively influence biofilm formation. Here, we elucidate the underlying mechanism by which ppGpp regulates EPS production by facilitating HpaR1 to modulate the expression of the gum cluster in the phytopathogen Xanthomonas campestris pv. campestris (Xcc). ppGpp affected the yield of EPS without influencing its primary or advanced structure, as confirmed by Fourier transform infrared spectroscopy and scanning electron microscopy. Expression of the gum cluster, which governs EPS biosynthesis in Xcc, was down-regulated in the ppGpp-deficient mutant (ΔrelAΔspoT) compared to the wild type (WT). Comparison of EPS production between knock-out mutants of the gum cluster and ppGpp-deficient mutant revealed that the gum cluster was a key determinant of EPS production, with ppGpp acting upstream of the gum cluster. Transcriptomic and qPCR analyses indicated that ppGpp modulated global transcription in Xcc, positively regulating expression of hpaR1, which encodes the transcription factor for the gum cluster. This regulatory role was further substantiated by electrophoretic mobility shift assays, which showed that ppGpp enhanced the DNA-binding activity of HpaR1. Furthermore, genetic complementation with hpaR1 restored EPS production, confirming its functional role in this regulatory pathway. In summary, these findings provide novel insights into the molecular mechanisms linking ppGpp signaling to EPS production in X. campestris pv. campestris.