Frontiers in Microbiology最新文献

Introduction: Hepatitis E virus (HEV) is a globally prevalent zoonotic pathogen posing major public health risks. Swine, a major meat source, carry HEV strains genetically similar to those in humans, highlighting the risk of zoonotic foodborne transmission. This study aimed to investigate the evolutionary history of HEV through phylogenetic and recombination analyses, further provide key reference bases for public health management, improve food safety standards, and offer support for developing effective strategies to prevent foodborne hepatitis E infections.

Methods: We analyzed 348 full-length genomes of HEV isolated from humans and pigs in Asia over the past three decades. Phylogenetic analysis was conducted using the neighbor-joining method in MEGA11. Recombination analysis was performed with seven methods in RDP4, and sequence similarity was visualized using Simplot.

Results: HEV-4 predominated in Asia, especially China, whereas HEV-3 was regionally endemic. Through genomic analysis, we identified 34 potential natural recombination events, predominantly occurring in the RNA-dependent RNA polymerase (RdRp) region; 14 events occurred between swine and human strains, supporting the hypothesis of cross-species transmission. Moreover, 20 recombination events occurred in China and mainly involved HEV-4 strains, suggesting that HEV has distinct evolutionary dynamics. The detection of five inter-genotypic recombination events may highlight ongoing genetic exchange within HEV populations in Asia, and the biological significance of these events remains to be determined.

Discussion: These findings highlight the importance of tracking the evolutionary dynamics of HEV through genomic surveillance, and further underscore the necessity of conducting ongoing HEV surveillance and research to inform prevention strategies.

The cysteine desulfurase (IscS) is a core component of the ISC iron-sulfur (Fe-S) cluster assembly system in Escherichia coli. Deficiency of IscS leads to serious growth defects in E. coli, along with reduced activity of Fe-S cluster-dependent enzymes. We previously demonstrated that the growth defect of IscS-deficient E. coli (ΔiscS) is completely restored by H₂S exposure, but the underlying molecular mechanism was not fully understood. Here, based on proteomic analysis, we identified 19 up-regulated Fe-S proteins in the ΔiscS mutant upon H₂S exposure, 13 of which are involved with energy metabolism. Correspondingly, H₂S exposure also enhanced the activity of Fe-S enzymes in the mutant. Metabolomic analysis revealed a remarkable increase in the levels of the energy metabolites NAD⁺, succinate, and leucine. These results implied that H₂S could restore cell proliferation and Fe-S cluster biosynthesis by compensating for the functional loss of IscS. We also constructed a series of mutants, each lacking a single component of the ISC assembly system. A key observation was that the ΔiscU mutant, deficient in the Fe-S cluster scaffold protein IscU, failed to have its growth defect rescued by H₂S exposure. These findings indicated that H₂S promotes Fe-S cluster biosynthesis on IscU, ruling out direct assembly on apoproteins. Moreover, Na₂S supplementation during recombinant expression of aconitase B in the ΔiscS mutant significantly increased its Fe-S cluster abundance and enzymatic activity. We also demonstrated that, unlike the ΔiscS mutant, deletion of sufS, which encodes the cysteine desulfurase of the SUF Fe-S cluster biogenesis system, did not significantly impair bacterial growth, and the resulting mutant's proliferation was not affected by H₂S exposure. Our study elucidates the mechanism by which H₂S exposure rescues the proliferation impairment of the ΔiscS mutant. Specifically, we demonstrate that H₂S functions as a sulfur donor for Fe-S cluster assembly, thereby compensating for the biosynthetic deficit.

Background: Alcohol-associated liver disease (ALD) is closely linked to gut microbiota dysbiosis. However, the specific microbial metabolic functions that drive the transition from microbial imbalance to hepatic inflammation and metabolic injury remain unclear, limiting the development of mechanism-based therapeutic strategies.

Methods: This study integrated human microbiome analysis with fecal microbiota transplantation (FMT) experiments in an ALD mouse model. Multi-omics approaches, including 16S rRNA gene sequencing, untargeted metabolomics, and immunological profiling, were employed to systematically characterize the interactions among gut microbiota composition, microbial-derived metabolites, and host immune responses.

Results: We observed that ALD progression was characterized by an early shift in microbial composition followed by a marked decline in microbial diversity, culminating in an ecological collapse of the gut microbiota. FMT from healthy donors significantly improved liver histopathology and serum biochemical parameters, accompanied by restoration of gut microbial diversity and key metabolic functions. Metabolomic analyses revealed enhanced short-chain fatty acid (SCFA) production and activation of α-linolenic acid (ALA)-related metabolic pathways following FMT. These metabolic improvements were associated with reduced inflammatory responses and improved immune homeostasis.

Conclusion: Our findings demonstrate that FMT from healthy donors ameliorates ALD by restoring critical microbial metabolic functions, particularly SCFA production and ALA-related pathways. These results highlight microbial metabolic function as a promising therapeutic target for microbiome-based interventions in ALD.

Introduction: The rise of drug-resistant tuberculosis poses a significant challenge in patient management. Epidemiological cut-off values define drug resistance in Mycobacterium tuberculosis. In our previous study, we reported deviations from the WHO-recommended epidemiological cut-off values and identified subtherapeutic concentrations of rifampicin in clinical Mycobacterium tuberculosis isolates. Building on these findings, the present study systematically evaluated the epidemiological cut-off values and pharmacodynamic profiles of newer and repurposed second-line anti-TB drugs - Bedaquiline, Delamanid, Moxifloxacin, Linezolid, Clofazimine, Levofloxacin, and Pretomanid against the first-line drug-sensitive and isolates that are resistant to Rifampicin and Isoniazid from tuberculosis patients in and around Chennai.

Methods: The Broth microdilution-based Microscopic Observation Drug Susceptibility assay was employed to determine the minimum inhibitory concentration of the drugs against well-characterized wild-type and drug-resistant clinical Mycobacterium tuberculosis clinical isolates. The resulting MIC profiles were subsequently analyzed to delineate pharmacodynamic relationships underlying therapeutic efficacy and resistance development.

Results and discussion: Deviations from the World Health Organization-recommended epidemiological cut-off values were observed, with lower thresholds for delamanid and levofloxacin and higher concentrations for clofazimine and bedaquiline. These shifts indicate region-specific susceptibility patterns in Mycobacterium tuberculosis that have direct implications for the effective treatment of multidrug-resistant tuberculosis. Inaccurate cut-off values may lead to misclassification of resistance, inappropriate regimen selection, and exposure to suboptimal drug concentrations, thereby compromising treatment efficacy and amplifying the risk of acquired resistance. Concordantly, pharmacodynamic analyses revealed sub-therapeutic exposure ranges for several newer and repurposed anti-TB drugs, underscoring the potential for treatment failure even in strains classified as susceptible. Collectively, these findings highlight the urgent need for regionally calibrated epidemiological cut-off values to optimize drug dosing, improve MDR-TB treatment outcomes, and strengthen resistance surveillance frameworks.

Background: Yunnan Province remains a region with a high prevalence of human immunodeficiency virus (HIV) in China. Due to shared transmission routes, HIV/Hepatitis C virus (HCV) co-infection is common. This study aimed to analyze the prevalence and mutation patterns of HIV-1 drug resistance among HIV/HCV co-infected patients specifically following the virological failure of first-line highly active antiretroviral therapy (HAART) in Yunnan, and to compare these characteristics with HIV-1 mono-infected patients.

Methods: A cross-sectional study was conducted among 104 HIV/HCV co-infected and 120 HIV-1 mono-infected patients who experienced virological failure (HIV-RNAgeq 1,000 copies/mL) after at least 6 months of ART. Genotypic drug resistance was tested using an in-house method and analyzed via the Stanford HIV drug resistance database. Multivariable logistic regression and stratified analysis were performed to adjust for confounders.

Results: Among patients with treatment failure, the drug resistance rate in the HIV/HCV co-infection group (37.5%) was significantly lower than in the HIV-1 mono-infection group (55.0%, P = 0.009). Multivariable logistic regression showed that HIV/HCV co-infection was associated with a lower trend of resistance, although it did not reach formal statistical significance after adjusting for gender, treatment duration, and CD4 + Count (aOR = 0.49, P = 0.084). However, stratified analysis revealed that co-infection was significantly associated with lower resistance in patients with a treatment duration of 6-12 months (OR = 0.24, P = 0.001) and those with CD4 + Count ≤ 350 cells/μL (OR = 0.38, P = 0.001). The frequency of the NRTI-related mutation T69D/N/S was significantly lower in the co-infected group (P = 0.029).

Conclusion: Among patients experiencing virological failure, HIV/HCV co-infection is associated with distinct genotypic resistance profiles, particularly in the early stages of treatment failure and among immunodeficient individuals. These findings suggest that co-infection status may influence the pathway to HIV drug resistance. Clinicians should prioritize prompt genotype resistance testing for co-infected patients failing ART to optimize second-line regimen adjustments.

The increasing demand for healthy non-conventional probiotic foods has positioned plant-based milk analogs as viable alternatives to traditional dairy products. In these matrices, fermentation with probiotic lactic acid bacteria (LAB) offers the opportunity to develop new functional foods with enhanced sensory, nutritional, and health properties. The present study aimed to develop a functional probiotic beverage by fermenting a cashew-based matrix with LAB isolated from kefir grains, characterizing its techno-functional and anti-inflammatory properties. A cashew-based beverage was prepared and subjected to various heat treatments before fermentation assays. Lacticaseibacillus paracasei CIDCA 8339 and CIDCA 83124, Lactiplantibacillus plantarum CIDCA 8327, and Lactococcus lactis subsp. lactis CIDCA 8221 were evaluated for beverage fermentation at 30°C. All strains achieved high counts (8-9 log CFU/mL), but only CIDCA 8327 and CIDCA 8339 reduced the pH to approximately 5.00-5.20. Notably, L. plantarum CIDCA 8327 demonstrated the ability to inhibit the growth of undesirable spore-forming microorganisms that survive pasteurization. The mixed-culture of CIDCA 8327 and CIDCA 8339 enhanced LAB growth and acidification (pH 4.53 after 24 h). This effect occurred with increased lactic and acetic acid production. This resulting fermented beverage exhibited a notably high protein (4.7%), fiber (1.8%), and lipid content (7.8%, with over 75% of unsaturated fatty acids) compared to commercial plant-based fermented beverages. The product exhibited colloidal stability for at least 1 month during refrigeration and showed a higher apparent viscosity (130.5 mPa.s) than its unfermented counterpart (102 mPa.s). Additionally, the non-microbial fraction from the fermented beverage successfully suppressed the inflammatory response by 85% in a Caco-2-ccl20:luc reporter system, a significant improvement over the 50% reduction seen with the unfermented product. This suggests that LAB produce bioactive metabolites, such as organic acids, which enhance the immunomodulatory effects. In conclusion, the cashew-based matrix is highly suitable for kefir-isolated LAB. However, selecting an appropriate starter culture is crucial for achieving a product with a low spoilage microbial load. In this context, fermentation with the mixed starter CIDCA 8327 and CIDCA 8339 resulted in a nutritious probiotic beverage with enhanced techno-functional characteristics and anti-inflammatory properties, indicating its potential as a functional food to support gastrointestinal health.

Introduction: Accurate detection of environmental microorganisms is key to ecological monitoring and public health risk assessment. Multispectral imaging yields rich biochemical and structural cues, yet its practical use is hampered by inter-band spectral heterogeneity and the small, visually similar traits of microorganisms objects. These issues impair cross-band feature alignment and discriminability, thus limiting the performance of existing detection frameworks.

Methods: To address these challenges, we propose a multispectral framework for fine-grained microorganisms detection named WPF-Mamba (Wavelet-Progressive Fusion Mamba). We design a novel Progressive Visual State Space Block (P-VSS Block). Built on the conventional VSS block, it integrates a Progressive Multi-Scale Feature Fusion (PMFF) unit to optimize hierarchical representations via stepwise context and semantic enhancement, improving subtle feature capture. WPF-Mamba further incorporates a Wavelet-based Multispectral Fusion (WMF) module, which fuses complementary spectral information through multi-scale wavelet decomposition and frequency-domain alignment, mitigating cross-band inconsistencies and enhancing microorganisms texture and spectral feature representation.

Results: Based on the EMDS-7 dataset, we extended the sample set by constructing high-quality infrared samples with generative adversarial networks and generative large language models, thus forming the extended multispectral microorganisms detection dataset EMDS-7-MS. Evaluation results on the EMDS-7-MS dataset demonstrate that our method further improves the mAP@50 by 2.9% compared with the baseline model, which verifies the effectiveness of our proposed method in the task of multispectral microorganisms detection.

Discussion: By addressing spectral misalignment and small-object representation limitations, WPF-Mamba offers a robust, generalizable approach for multispectral microorganisms detection. Specifically, its wavelet-based fusion and progressive feature refinement strategy presents a practical paradigm for multispectral fine-grained microorganisms analysis, which in turn contributes to the development of reliable, scalable environmental monitoring systems.

Biocorrosion, also known as microbiologically influenced corrosion (MIC), is the deterioration of metals caused by microbial activities that compromise the structural integrity, reliability, and safety of steel infrastructure. To identify the genetic determinants that MIC-causing microorganisms may use to attack steel infrastructure, field samples from natural gas infrastructure with a potential history of MIC were collected, enriched for different MIC categories, and subjected to whole-genome shotgun sequencing for metagenomic analysis. Biofilms were grown on carbon steel coupons or glass slides as attachment substrates to assess differences in microbial community composition and metabolic activities. The highest corrosion activities were observed in enrichments dominated by acid-producing bacteria (APB) and hydrogen-utilizing bacteria. APB enrichments resulted in the highest accumulation of organic acids and a severe decrease in culture fluid pH. A total of 57 metagenome-assembled genomes were recovered from the biofilms, some of which differed between carbon steel coupons and glass slide substrates. The metagenomes contained most of the known genes implicated in MIC and sulfide production, with substantial variation in estimated gene copy numbers among metagenomes and attachment substrates. Overall, comparative analysis of these biofilm metagenomes enriched from natural gas production and processing infrastructure highlights similarities to microbial communities commonly observed in oil production and processing systems and provides an overview of candidate genes that may be used as molecular probes for MIC.

Objective: To systematically investigate the pooled prevalence of Small Intestinal Bacterial Overgrowth (SIBO) in patients with Irritable Bowel Syndrome (IBS) compared to healthy individuals and to evaluate the therapeutic efficacy of rifaximin in IBS patients with concomitant SIBO.

Methods: A comprehensive computer-based search was conducted across databases including PubMed and Embase from their inception until December 2025. Relevant cohort studies, case-control studies, and cross-sectional studies were included. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). Meta-analysis was performed using a random-effects model.

Results: A total of 25 studies were included. The pooled risk of SIBO was significantly higher in IBS patients compared to healthy controls (OR = 5.71, 95% CI: 3.45-9.45). The Glucose Hydrogen Breath Test (GBT) subgroup showed a higher odds ratio and lower heterogeneity. Rifaximin treatment achieved a pooled SIBO eradication rate of 59% (95% CI: 0.48-0.68), with the medium-to-high dose group (≥ 1,200 mg/day) showing a slightly superior efficacy compared to the lower-dose group.

Conclusion: A significant association exists between SIBO and IBS. Rifaximin is an effective treatment for IBS patients with concomitant SIBO. The substrate choice for SIBO diagnosis involves a trade-off: while GBT offers greater diagnostic stability and specificity, LBT provides broader sensitivity for distal overgrowth. This evidence-based nuance should guide clinical substrate selection based on the diagnostic priority.

Systematic review registration: INPLASY.COM, identifier NPLASY202630002.