Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the CNS whose risk and course are shaped by both genetic and environmental factors, among which the intestinal microbiota has emerged as a key, potentially modifiable contributor. People with MS frequently display altered gut microbiota, characterized by depletion of fiber-fermenting, short-chain fatty acid (SCFA)-producing commensals, and expansion of taxa associated with mucus degradation and proinflammatory metabolism. These compositional shifts are paralleled by broad changes in blood and CSF metabolites, including reduced SCFAs, tryptophan-derived aryl hydrocarbon receptor ligands, and secondary bile acids. In addition, several reports highlight the accumulation of aromatic amino acid-derived phenolic and indolic compounds and specific lipid mediators linked to neuroinflammation and neurodegeneration. In this up-to-date review, we synthesize evidence from experimental models and human studies showing how microbial metabolites can influence MS pathogenesis through converging mechanisms: modulation of gut and blood-brain barrier integrity; shaping of T-cell and B-cell responses; direct effects on microglia, astrocytes, and oligodendrocyte lineage cells after crossing into the CNS; and modulation of neural circuits, particularly those involving the vagus nerve. Finally, we highlight current gaps, including the need for longitudinal, harmonized multiomic cohorts, and mechanistic studies integrating microbiome, metabolome, and host readouts across gut, blood, and CNS. Overall, available data support a model in which coordinated disruption of the gut microbiota-metabolite axis, rather than any single pathogen, contributes to MS, opening avenues for microbiota-based and metabolite-based biomarkers and therapies aimed at restoring immune and neuroglial homeostasis.

Sepsis, a common consequence of bloodstream infection (BSI), is a leading cause of global mortality and morbidity. Diagnosis is challenging and slow due to extremely low pathogen loads and reliance on time-consuming blood culture, necessitating empiric therapy that worsens outcomes and antimicrobial resistance. Here, we introduce sedimentation-assisted tandem rocking and enrichment for analysis and monitoring (STREAM), a platform that efficiently isolates and enriches pathogens near their natural doubling times directly from whole blood. By integrating STREAM with single-cell analysis, we achieved rapid and robust diagnosis of BSI from whole-blood samples. Using molecularly barcoded sequential fluorescence in situ hybridization, pathogen identification in 104 positive blood culture samples showed 96.15% concordance with clinical laboratory results. Gel-based single-cell antimicrobial susceptibility testing yields 97.96% essential agreement and 93.9% categorical agreement across 219 drug-dose combinations. The platform enabled comprehensive BSI diagnosis directly from whole blood, achieving a detection limit as low as 0.1 to 1 CFU/ml and delivering full diagnostic results within 6.75 to 17 hours.

The role of symbiotic algae in coral life history and host health is well documented, but the immune and physiological trade-offs of hosting these symbionts remain less explored. While association with the algal symbionts of the genus Durusdinium is known to confer thermotolerance, it has also been linked to coral tissue loss under stress. We investigated whether algal type influences host immunity and stress responses in the tropical coral Pocillopora acuta. Durusdinium-hosting (D-hosting) P. acuta have distinct transcriptomic profiles, higher immune-related gene expression, and elevated baseline levels of immunity transcription factor nuclear factor κB as compared to corals hosting Cladocopium (C-hosting). Under heat challenge, D-hosting P. acuta exhibited tissue loss, oxidative stress, and immune and microbial dysregulation, whereas C-hosting P. acuta were more susceptible to bleaching, metabolic dysregulation, and decline in nitrogen-fixing and antioxidant-producing bacteria. Last, infection with the bacterium Vibrio coralliilyticus caused high tissue loss in D-hosting corals but not in C-hosting corals. Our results suggest a mechanism for how Durusdinium association enhances thermotolerance yet predisposes corals to tissue damage under stress, suggesting immune trade-offs that can compromise host survival under multiple stressors.

Pathogens sense host stress hormones in the gut and use them to regulate motility and virulence. A new study in PLOS Biology transfers this pathway to Escherichia coli Nissle and redesigns its regulation to drive programmable outputs.

Chronic obstructive pulmonary disease (COPD) is featured by persistent airflow limitation and chronic inflammation. Considerable evidence highlights the role of the gut-lung axis, suggesting that disruption of gut microbial balance may contribute to aggravated systemic and pulmonary inflammation. This research intended to assess the impacts of a structured gut-lung axis-targeted nursing intervention on immune-inflammatory parameters, gut microbiota, and clinical outcomes in patients with stable COPD. The study involved the randomization of 115 patients to either the intervention or control group in a 1:1 ratio. The intervention group received a 12-week multimodal program, which included personalized high-fiber/probiotic nutrition, customized exercise plans, and stress management techniques. Patients in the control group did not receive the multimodal program and instead received routine care. The findings indicated that the intervention notably lowered serum IL-6, TNF-α, and CRP. Microbiome analysis further revealed that the intervention significantly enhanced α-diversity (Shannon and Chao1), enriched beneficial butyrate-producing genera (Faecalibacterium, Roseburia, and Bifidobacterium), and reduced the relative abundance of potential pathogens (Enterobacteriaceae), indicating a favorable shift in gut microbial ecology. Compared with the control group, the intervention group also experienced fewer moderate-to-severe exacerbations and showed greater sustained improvement in quality of life (SGRQ and CAT scores). In summary, a comprehensive nursing strategy centered on the gut-lung axis can regulate gut microbiota, alleviate systemic inflammation, lead to a reduction in exacerbation frequency and an improvement in the quality of life among patients with stable COPD, thus presenting a promising supplementary strategy to conventional care.

Four novel bacterial strains representing two novel species were isolated from in situ coal samples. Comparative analysis of 16S rRNA gene sequences showed that strains W1153T and W1478 share the highest sequence similarity with Leucobacter tardus K 70/01T (98.3%), whereas strains Z1108T and W1038 share the highest sequence similarity with L. tardus K 70/01T and Leucobacter exalbidus K-540BT (98.0%). Phylogenetic analysis based on 16S rRNA gene sequences and a core-genome phylogeny constructed from 665 core genes demonstrated that the four strains form two distinct clades, clearly separated from other species within the genus Leucobacter. Whole-genome sequencing revealed genome sizes ranging from 2.6 to 2.8 Mb, with G+C contents of 62.5-63.5 mol%. The average nucleotide identity and digital DNA-DNA hybridization values between the four strains and all recognized species within the genus Leucobacter ranged from 71.1 to 75.6% and 19.3 to 25.6%, respectively. The major cellular fatty acids of the four strains were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0. The respiratory quinone types were MK-11 for strain W1153T and MK-9(H8) for strain Z1108T. The main cell-wall sugars were rhamnose and ribose, with 2,4-diaminobutyric acid present as the diagnostic diamino acid. Based on phenotypic characteristics, phylogenetic analyses and chemotaxonomic evidence, strains W1153T and W1478, and Z1108T and W1038, are proposed as representing two novel species within the genus Leucobacter, named Leucobacter shiyiweii sp. nov. and Leucobacter fengyongliangi sp. nov., respectively. The type strains are W1153T (=GDMCC 1.5845T=KCTC 59606T) and Z1108T (=GDMCC 1.5846T=KCTC 59607T).

Trichothecium roseum is a highly destructive postharvest pathogenic fungus that causes pink mold rot in various fruit and leads to significant agricultural and economic losses. Phytoene is crucial for phytopathogens, but the molecular mechanism by which the phytoene synthase gene crtB regulates fungal pathogenicity remains largely unclear. In this study, we evaluated the functions of TrcrtB a phytoene synthase, in T. roseum via in vivo and in vitro assays. Our results showed that knock-out of TrcrtB showed inhibition of production of phytoene and its relevant downstream metabolites, such as lycopene, carotenes and carotenal, resulting in colorless colony and branching at the mycelial edges in the knockout mutant ΔTrcrtB. Compared with the wild type (WT) strain, the colony expansion was significantly reduced 35% at 5 days post-inoculation (dpi), and conidiation was notably decreased to 45%, 36%, and 70% at 3, 5, and 7 dpi in ΔTrcrtB in vitro. Scanning electron microscope observation revealed similar results. Moreover, the ΔTrcrtB showed higher sensitivity to abiotic stresses than WT, as evidenced by inhibition rates of ΔTrcrtB colony expansion up to 71.76% (menadione), 47.73% (Congo red), 23.01% (SDS), and 17.13% (KCl). The pathogenicity of ΔTrcrtB was dramatically impaired by decreasing the rotten area up to 85.26% on apple fruit and 70.30% on pears fruit. These results suggest that TrcrtB and phytoene are critical for development, stress tolerance and pathogenicity of T. roseum. Collectively, our study highlights the roles of TrcrtB and phytoene in the pathogenic fungus T. roseum, providing new insights into the molecular mechanisms of pink rot pathogenesis.

Background: Streptococcus suis serotype 2 is a major zoonotic pathogen responsible for severe systemic infections in pigs and humans, including septicemia, meningitis, and high mortality outcomes. Cefquinome, a fourth-generation β-lactam antibiotic widely used in veterinary medicine, is commonly applied for the treatment of S. suis infections. However, optimized dosing strategies remain insufficiently defined, particularly under conditions of varying bacterial burden, inoculum size, and reduced susceptibility or resistance phenotypes. These factors may significantly alter pharmacodynamic responses and compromise the predictive value of conventional MIC-based approaches. Objectives: This study aimed to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of cefquinome against S. suis serotype 2 using an integrated ex vivo serum time-kill experiments and semi-mechanistic PK/PD modeling. A secondary objective was to evaluate optimized dosing regimens across different inoculum levels and susceptibility phenotypes, including a cefquinome-resistant mutant. Methods: Cefquinome pharmacokinetics following intramuscular administration at 2 and 4 mg/kg in piglets were described using a two-compartment model. Dose proportionality, exposure linearity, and clearance parameters were assessed. Ex vivo serum time-kill experiments were conducted using a parental strain and a cefquinome-resistant mutant (M1) under normal-inoculum (NI), high-inoculum (HI), and mutant/resistant (MS) conditions. A semi-mechanistic PK/PD model incorporating logistic bacterial growth, sigmoidal Emax killing, nutrient limitation, and a time-delay function was developed to describe dynamic bacterial responses. Model parameters (k0, kmax, EC50) were estimated using nonlinear least-squares regression (Scientist v2.0), and simulations were performed by integrating time-varying PK input functions. Results: Cefquinome demonstrated linear pharmacokinetics with dose-proportional increases in Cmax and AUC between 2 and 4 mg/kg, with comparable clearance across doses. Ex vivo studies revealed time-dependent antibacterial activity with a pronounced inoculum effect. Higher bacterial burdens significantly reduced bactericidal efficiency and promoted regrowth during declining drug exposure. No tested concentrations achieved ≥3-log10 killing in HI or MS conditions, whereas the NI group achieved a maximal reduction of 3.5-log10 CFU/mL. MIC values in serum and medium were consistent (0.03, 0.06, and 0.24 µg/mL for NI, HI, and MS, respectively), indicating minimal protein binding influence. The semi-mechanistic model accurately described observed bacterial dynamics (R2 > 0.99; MSC > 1.5), capturing delayed drug effects, inoculum-dependent growth suppression, and regrowth phenomena. Growth rates were reduced under serum conditions, reflecting nutrient limitation. Importantly, inoculum size exerted a stronger impact on pharmacodynamic outcomes than resistance phenotype, as reflected by reductions in kmax and increases in EC50 under HI conditions. Although %T>MIC exceeded conventional β-lactam targets (>40%) in most regimens, MIC-based indices poorly correlated with observed dynamic killing responses. Conclusions: Cefquinome exhibited time-dependent antibacterial activity against S. suis serotype 2, strongly modulated by inoculum size and reduced susceptibility. The developed semi-mechanistic PK/PD model provided robust prediction of bacterial time-kill behavior and outperformed MIC-based metrics in guiding dose optimization. Simulation results support 2 mg/kg every 24 h for normal infections and 2 mg/kg every 12 h for high-inoculum or less susceptible infections, emphasizing the value of model-informed dosing strategies for optimizing β-lactam therapy.

Methicillin-resistant Staphylococcus aureus (MRSA) infections contribute significantly to the mortality rate associated with antimicrobial resistance, while also increasing medical complications when compared to methicillin-sensitive isolates. Consequently, increasing the efficacy of β-lactams may alleviate the burden associated with this drug-pathogen combination. Dialysed extracts, derived from Pelvetia canaliculata, were further partitioned to generate phlorotannin enriched extracts (PEEs). Minimum inhibitory concentrations (MICs) of extracts were used to determine the antimicrobial and antibiotic-modulating activity against seven clinical MRSA isolates. Whole-transcriptomic sequencing was carried out to determine potential mechanisms of action on the strongest extract-antibiotic combination against an MRSA isolate, determined by the fractional inhibitory concentration index (FICI). The most pronounced β-lactam modulatory effects were seen in the >100 kDa PEE from P. canaliculata in conjunction with amoxicillin (MIC fold-reductions = 12.8-214), while >30 kDa PEE resulted in the strongest FIC index value when combined with penicillin (0.23), indicating a synergistic effect. Whole-transcriptome analysis of this treatment identified multiple differentially expressed genes (Log2FC +1/-1) of statistical significance (p adj < 0.05), namely related to accelerated autolysis, cell-envelope stability, protein synthesis, DNA replication, iron homeostasis and active transport. This study highlights preliminary transcriptomic evidence of biological processes associated with penicillin modulation by P. canaliculata > 30 kDa PEE, providing a foundation for further investigation of its antibiotic-modulating activity.

Antarctic marine-derived fungi represent an underexplored reservoir of bioactive secondary metabolites shaped by extreme environmental pressures. In this study, nine fungal isolates obtained from Antarctic macroalgae, lichens, sponge tissue, and sediments were evaluated for their antimicrobial, anticancer, antibiofilm, and metabolomic profiles. Untargeted LC-MS/MS molecular networking (GNPS) revealed a chemically rich metabolome, dominated by alkaloids, followed by polyketides, meroterpenoids, and diketopiperazines, with Penicillium crustosum (A15A) emerging as a major biosynthetic contributor. The annotation of structurally diverse metabolites, including roquefortines, viridicatin derivatives, andrastins, and multiple diketopiperazines, highlights the metabolic plasticity of Antarctic fungi. Anticancer evaluation indicated cytotoxicity, with Aspergillus awamori (A30), Alternaria malorum (A36), and Cladosporium malorum (A38) displaying activity toward HCT 116 colorectal cancer cells at IC50 ≥ 30 µg/mL. Extracts were screened against methicillin-resistant Staphylococcus aureus (MRSA, COL), methicillin-susceptible S. aureus (MSSA, NCTC8325 4), and Escherichia coli K12, revealing low to no activity against these pathogens. Six of the nine isolates exhibited strong antibiofilm activity without inhibiting planktonic bacterial growth, indicating selective biofilm inhibition against MSSA and meeting the criteria for clinical developmental "hits". Biofilm inhibition ranged from 81.10% to 98.50%, with A15A showing the highest activity (98.50% at 250 µg/mL), followed by A36 (91.16% at 31.35 µg/mL). Botrytis sp. (A22A), P. chrysogenum (A7), Ulocladium microsporum (A24B), and A30 also demonstrated strong antibiofilm activity (81.10-85.89%). To our knowledge, this is the first report describing antibiofilm activity of Antarctic fungal extracts.

Fusarium graminearum, the major pathogen causing maize ear rot, severely threatens food security. Targeted gene deletion was used to characterize physiological functions of FgSRE1 in this pathogen. Transcriptomic profiling was conducted on axenic wild-type and ΔFgSRE1 cultures, plus maize ear tissues colonized by both strains. Nine core DEGs functionally annotated to transmembrane transport, membrane homeostasis and oxidative stress pathways were selected for qRT-PCR validation, including four upregulated genes encoding putative transferases and five downregulated transporter genes. Phenotypic assays revealed that the ΔFgSRE1 mutant displayed severe defects in conidial and ascospore production, along with drastically weakened pathogenicity on maize ears and leaves versus wild-type and complemented strains. qRT-PCR analysis confirmed consistent expression trends with the RNA-seq data: four putative transferase-encoding genes were up-regulated, whereas five genes related to membrane and redox transport were repressed. Together, the genetic and phenotypic results demonstrate that FgSRE1 contributes to reproductive development and virulence in F. graminearum, whereas the transcriptomic data suggest potential associations with metabolic, redox, and membrane-transport-related pathways. Our findings provide a basis for investigating the FgSRE1-associated virulence network and developing eco-friendly maize ear rot control strategies.

Postharvest soft rot is a major constraint in kiwifruit production, causing substantial economic losses and raising food safety concerns. Therefore, the development of sustainable biocontrol alternatives to conventional chemical treatments is urgently needed. In this study, thirty-seven fungi were isolated from healthy kiwifruit tissues and rhizosphere soil and screened for their biocontrol potential. Three highly effective antagonistic strains were ultimately identified: Mucor circinelloides N2-1-1, Aspergillus niger Pb-2-2, and Trichoderma hamatum Nd-1-1. In vitro antagonism assays showed that A. niger Pb-2-2 exhibited the strongest and broadest-spectrum inhibitory activity against four postharvest pathogens, namely Fusarium sp., Alternaria sp., Botryosphaeriaceae sp., and Phomopsis sp. In contrast, in vivo protection assays demonstrated that T. hamatum Nd-1-1 almost provided the highest control efficacy against all four pathogens in kiwifruit fruit. Fermentation broth protection experiments further revealed that A. niger Pb-2-2 produced stable and broad-spectrum antimicrobial metabolites. Although M. circinelloides N2-1-1 showed the weakest antagonistic activity among the three fungi, this is the first report indicating that M. circinelloides has antagonistic activity against phytopathogenic fungi. Physiological analyses indicated that all three antagonistic fungi alleviated the inhibitory effects of pathogens on superoxide dismutase, catalase, and ascorbate peroxidase activities, helped maintain reactive oxygen species homeostasis, and activated the phenylpropanoid pathway, thereby enhancing disease resistance in kiwifruit. These findings provide a theoretical basis and promising microbial resources for the biological control of postharvest soft rot in kiwifruit.

The genus Cladosporium represents one of the largest genera of dematiaceous hyphomycetes, which are commonly found on plants. The species comprising this group predominantly function as plant endophytes, producing important bioactive compounds, or act as pathogens damaging crops of significant economic interest. Nevertheless, their association with Camellia spp. remains to be fully elucidated, with only seven recorded cases mentioning three known species. During an investigation into fungi associated with tea plant, several Cladosporium isolates were obtained from symptomatic leaves of Camellia sinensis cv. Fenghuang Dancong. Using a polyphasic approach that combined morphological observations with multi-locus phylogenetic analyses based on the internal transcribed spacer (ITS), actin (act), and translation elongation factor 1-α (tef1-α), these isolates were identified as three new species in the C. cladosporioides complex, namely C. dancongensis sp. nov., C. fenghuangensis sp. nov., and C. leptosporum sp. nov. These new species can be distinguished from their close relatives (e.g., C. benschiae, C. dracaenae, C. kuwanaspidi, and C. tenuissimum) by distinct morphological features such as conidial dimensions, mycelial width, and colony characteristics. This study expands the understanding of fungi associated with Camellia sinensis and is the first case in which new Cladosporium species inhabit tea plants. Moreover, it will facilitate further research into the phylogenetic relationships of these new species and their role relative to tea plant disease.