Microbiology spectrum最新文献

{"title":"<i>Candida auris</i> colonization among critically ill neonatal intensive care unit patients in Dhaka, Bangladesh.","authors":"Fahmida Chowdhury, Syeda Mah-E-Muneer, Sanzida Khan, Alexander Jordan, Gazi Md Salahuddin Mamun, Shawn R Lockhart, Zakir Hossain Habib, Aninda Rahman, Kamal Hossain, Zakiul Hassan, Tahmina Shirin, Sajeda Prema, Md Aminul Islam, Dilruba Ahmed, Debashis Sen, Muhammed Ashraful Alam, Md Abdul Baki, Tahsinul Amin, Mahmudur Rahman, Meghan Lyman","doi":"10.1128/spectrum.00129-25","DOIUrl":"https://doi.org/10.1128/spectrum.00129-25","url":null,"abstract":"<p><p><i>Candida auris</i> is a multidrug-resistant yeast causing invasive infection and healthcare-associated outbreaks globally. We aimed to estimate the extent of <i>C. auris</i> colonization and infection among neonates in selected neonatal intensive care units (NICUs) in Dhaka City. We conducted a prospective study from August 2021 to September 2022. Skin swabs and blood samples were collected from NICU patients. <i>C. auris</i> was identified using CHROMagar and VITEK-2. Patient characteristics and healthcare histories were recorded. Of 374 patients enrolled, 32 (9%) were colonized with <i>C. auris</i>, and one (0.3%) developed a bloodstream infection (BSI). The median age of the enrolled patients was 4 days (IQR: 2-8); 60% were male. Among the colonized patients, 44% (14/32) were colonized at enrollment, and 56% (18/32) became colonized after enrollment, occurring 3-19 days after admission. Of patients colonized on admission, five (36%) were admitted from the obstetric ward, eight (57%) from another hospital, and one (7%) from home. Seven (22%) of the 32 colonized patients, including the one with BSI, died. All deaths occurred in public hospitals. Three (9%) <i>C. auris</i> isolates demonstrated resistance to two antifungal drug classes. Our findings suggest frequent transmission of <i>C. auris</i> within the NICU, as demonstrated by more than half of the patients acquiring colonization after 48 h of admission. The high rate of <i>C. auris</i> transmission underscores the critical need for improved patient detection and robust infection prevention and control measures. Further investigation into <i>C. auris</i> transmission dynamics is crucial to inform prevention strategies.IMPORTANCE<i>Candida auris</i> is a serious fungal pathogen that is resistant to multiple antifungal medications. It is a significant concern in healthcare settings, particularly in neonatal intensive care units (NICUs) where vulnerable newborns are at increased risk of infection. This may be a serious public health issue due to its high mortality, limited treatment options, risk of transmission, and strain diversity.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0012925"},"PeriodicalIF":3.8,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum for Okutani et al., \"Genetic diversity and virulence of <i>Bacillus cereus</i> group isolates from bloodstream infections\".","authors":"Akiko Okutani, Shu Okugawa, Fumie Fujimoto, Mahoko Ikeda, Takeya Tsutsumi, Kyoji Moriya, Ken Maeda","doi":"10.1128/spectrum.02937-25","DOIUrl":"https://doi.org/10.1128/spectrum.02937-25","url":null,"abstract":"","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0293725"},"PeriodicalIF":3.8,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic and pathological insights into the first identified genotype IIIb chicken anemia virus strain in Bangladesh.","authors":"Marjana Akter, Roni Mia, S M Nazmul Hasan, Anandha Mozumder, Nurejunnati Jeba, Raduyan Farazi, Farzana Akter, Sharmin Akter, Md Zaminur Rahman, Sukumar Saha, Tofazzal Islam, Md Golzar Hossain","doi":"10.1128/spectrum.00796-25","DOIUrl":"https://doi.org/10.1128/spectrum.00796-25","url":null,"abstract":"<p><p>Chicken anemia virus (CAV) is a highly infectious pathogen that causes severe immunosuppression and significant economic losses in poultry, with limited genomic data in Bangladesh hindering effective disease control. This study characterizes a CAV strain from a field outbreak in Bangladesh through clinical, pathological, and molecular analyses, including genome sequencing, genotyping, and assessment of viral protein structure. Clinically suspected chickens exhibiting anemia, depression, pale combs, and cyanotic wings underwent gross and histopathological examinations. Viral DNA was extracted from bone marrow samples and analyzed using PCR, followed by complete genome sequencing with next-generation sequencing. Phylogenetic analysis, genotyping, mutational profiling, and structural predictions of viral proteins (VP1, VP2, and VP3) were performed to assess evolutionary relationships and pathogenic potential. Histopathology confirmed severe lymphoid depletion in the thymus, spleen, and bursa of Fabricius, consistent with CAV-induced immunosuppression. Molecular detection confirmed CAV presence in eight out of ten samples. Whole-genome analysis revealed a 2,330 bp genome with 42% GC content, clustering within genotype IIIb and showing close genetic relatedness to a Chinese strain. Mutational analysis revealed several nucleotide substitutions in the viral genomes, with the highest number of amino acid changes observed in the VP3 protein. Computational modeling revealed minor structural variations in VP1 and VP2, which may affect antigenicity and phosphatase activity. This study provides the complete genome characterization of a Bangladeshi CAV strain, revealing critical genetic variations that may influence viral virulence. The findings underscore the need for enhanced surveillance and targeted vaccine strategies to mitigate CAV-related losses in poultry.</p><p><strong>Importance: </strong>This study provides the first complete genomic characterization of a genotype IIIb chicken anemia virus (CAV) strain in Bangladesh. By integrating clinical, pathological, and molecular analyses, the research identifies critical genetic variations that could influence viral virulence, immune evasion, and disease severity. The findings highlight the close genetic relationship between this Bangladeshi strain and a previously reported Chinese strain, suggesting potential epidemiological links. Furthermore, the study underscores the need for enhanced surveillance and targeted vaccine strategies to mitigate CAV-induced immunosuppression and economic losses in poultry farming. The insights gained from this research contribute to a deeper understanding of CAV evolution and could inform future diagnostic and control measures to protect poultry populations.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0079625"},"PeriodicalIF":3.8,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Streamlined extraction of nucleic acids and metabolites from low- and high-biomass samples using isopropanol and matrix tubes.","authors":"Caitriona Brennan, Justin P Shaffer, Pedro Belda-Ferre, Ipsita Mohanty, Yuhan Weng, Kalen Cantrell, Gail Ackermann, Celeste Allaband, MacKenzie Bryant, Sawyer Farmer, Antonio González, Daniel McDonald, Cameron Martino, Michael J Meehan, Gibraan Rahman, Rodolfo A Salido, Tara Schwartz, Se Jin Song, Caitlin Tribelhorn, Helena M Tubb, Pieter C Dorrestein, Rob Knight","doi":"10.1128/spectrum.01912-25","DOIUrl":"https://doi.org/10.1128/spectrum.01912-25","url":null,"abstract":"<p><p>An essential aspect of population-based research is collecting samples outside of a clinical setting. This is crucial because microbial populations are highly dynamic, varying significantly across hosts, environments, and time points, a variability that clinical sample collection alone cannot fully capture. At-home sample collection enables the inclusion of a larger and more diverse group of participants, accounting for differences in ethnicity, age, and other factors. However, managing large studies is challenging due to the complexities involved in sample acquisition, processing, and analysis. Building on our previous work demonstrating the effectiveness of single 1 mL barcoded, racked Matrix Tubes in reducing sample processing time and well-to-well contamination for paired DNA and metabolite extraction, we further validate this method against a previously benchmarked plate-based approach using the same extraction reagents. This validation focuses on samples from the built environment, human skin, human saliva, and feces from mice and humans. Importantly, we explore the impact of using a mix of bead sizes during bead-beating for cell lysis, demonstrating that it enhances taxonomic recovery compared to a single bead size. Finally, we assess the potential of 95% isopropanol for room-temperature sample preservation. Our results show that isopropanol performs comparably to 95% ethanol in many cases, suggesting it is viable as an alternative when ethanol is unavailable. Beyond minimizing contamination, halving processing time, eliminating human error during sample plating, and streamlining metadata curation, the Matrix tube approach produces metabolomic, 16S, and shotgun metagenomic data consistent with the Plate-based Method for both high- and low-biomass samples.</p><p><strong>Importance: </strong>Numerous studies have linked the microbiome to human and environmental health, yet many fundamental questions remain unanswered. Large-scale studies with robust statistical power are required to identify important covariates against a background of confounding factors. Cross-contamination, limited throughput, and human error have been identified as major setbacks when processing large numbers of samples. We present a streamlined method for sample accession and extraction of metabolites and DNA for both high- and low-biomass samples. This approach, previously shown to significantly reduce cross-contamination, employs an automation-friendly, single barcoded tube per sample. Additionally, we demonstrate that 95% isopropanol serves as an effective ambient-temperature storage solution for many sample types, providing an alternative in regions where ethanol is unavailable or restricted. This method has significant implications for the field, enabling large-scale studies to generate accurate insights with greater efficiency and expanded accessibility in situations in which ethanol is more costly or otherwise not available.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0191225"},"PeriodicalIF":3.8,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reproducible 3D bioprinting of <i>Streptococcus mutans</i> to create model oral biofilms.","authors":"Guilherme Roncari Rocha, Danielle S W Benoit, Anne S Meyer","doi":"10.1128/spectrum.00935-25","DOIUrl":"https://doi.org/10.1128/spectrum.00935-25","url":null,"abstract":"<p><p>Novel approaches are needed to study relationships between oral biofilm strains, enable three-dimensional oral biofilm deposition, and hasten the rigor and pace of basic and translational biofilm studies. Previously, 3D-bioprinters were leveraged to deposit spatially patterned biofilms onto sugar-rich agar surfaces to study how the underlying spatial organization of various microbes impacts biofilm persistence and virulence. Herein, we have developed a new method to adapt this process from limited, soft agar surfaces to biomimetic solid substrates submerged in aqueous solutions for studying oral biofilms <i>in vitro. Streptococcus mutans</i> UA159 was used to compare standard <i>in vitro</i> biofilm development with our new 3D-printed bio-ink hydrogels on hydroxyapatite disks, which mimic tooth surfaces. Biofilms formed using the bio-ink methodology showed minimal quantitative differences in virulence factors, including environmental pH, biomass, and cell density, compared to biofilms formed using the standard <i>in vitro</i> methodology. The bio-ink technique resulted in higher exopolysaccharide deposition, a key virulence factor for biofilm cohesion and protection, as well as more homogeneous spatial distribution of bacterial microcolonies. Our newly developed technique produces 3D-printable model biofilms that match the virulence benchmarks of the standard method, opening possibilities to print biofilms onto any substrate and a new way to study multidimensional biofilm dynamics.IMPORTANCEDental caries is the most common oral disease caused by biofilms in humans with cost limitations. Changes in the human diet have increased the exposure to sugar-rich processed food, increasing the incidence and severity of dental caries and creating greater rationale for understanding biofilm deposition, microbial interactions, and maintenance of quiescence of the oral microbiota. Recent 3D-printing techniques have been leveraged to develop the first model biofilms, providing spatial control over microbe deposition and enabling unprecedented investigation of the impact of cell-cell interactions and spatial organizationupon biofilm persistence, sensitivity to drugs, and virulence. Here, we have developed new methods to extend bioprinting to oral biofilms using cariogenic <i>Streptococcus mutans</i>. Our technique is an attempt to establish an alternative method for oral biofilm formation <i>in vitro</i> that uses 3D-printing tools, preserving the virulence of standard <i>in vitro</i> biofilms while amplifying the availability and versatility of methods for understanding the microbiome.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0093525"},"PeriodicalIF":3.8,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145275298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative gene expression analysis in closely related dermatophytes reveals secondary metabolism as a candidate driver of virulence.","authors":"Lenka Machová, Martin Kostovčík, Karel Švec, Vít Hubka, Miroslav Kolařík, Adéla Wennrich","doi":"10.1128/spectrum.01383-25","DOIUrl":"https://doi.org/10.1128/spectrum.01383-25","url":null,"abstract":"<p><p>Dermatophytes are important fungal skin pathogens affecting humans and animals worldwide. Although several virulence factors have been identified using genomic, proteomic, and transcriptomic approaches, their roles remain incompletely understood. In this study, we applied a comparative approach using four closely related taxa within the <i>Trichophyton benhamiae</i> complex, which differ in infectivity despite sharing common hosts. We focused on the emerging zoonotic pathogen <i>T.benhamiae</i> var. <i>luteum</i>, currently responsible for epidemic outbreaks in Europe, and compared it to its less infective relatives. A set of 16 candidate genes, informed by preliminary transcriptomic screening, was assessed via RT-qPCR across 12 strains grown <i>in vitro</i> (Sabouraud dextrose broth) and <i>ex vivo</i> (murine skin explants). Genes associated with secondary metabolism were consistently upregulated under <i>ex vivo</i> conditions, particularly in <i>T.benhamiae</i> var. <i>luteum</i>. While two of the biosynthetic gene clusters examined are linked to known metabolites, others remain uncharacterized. These findings reveal key gene expression differences that may explain the enhanced infectivity of emerging strains and underscore the potential role of secondary metabolites in dermatophyte virulence. They also highlight the need for improved genome annotation in <i>T.benhamiae</i> to better understand the molecular basis of pathogenesis.IMPORTANCE<i>Trichophyton benhamiae</i> var. <i>luteum</i> is an emerging fungal pathogen responsible for a rising number of skin infections transmitted from guinea pigs to humans, especially in Europe. We investigated why this pathogen spreads more effectively than its close relatives, which infect the same hosts but are less epidemic. Using a laboratory model that mimics skin infection, we found that genes involved in producing fungal compounds-called secondary metabolites, some of which act as toxins-are more active in this pathogen. These compounds may help the fungus suppress the host immune response and establish infection. Our findings shed light on how fungal pathogens adapt to their hosts and highlight gene pathways that could be targeted in future diagnostics or treatments. Understanding these mechanisms is key to managing emerging fungal threats in both animals and humans.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0138325"},"PeriodicalIF":3.8,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disulfiram inhibits poxvirus extracellular virus production by targeting the palmitoylation sites on F13.","authors":"Ting Xu, Junwen Luan, Yao Hou, Leiliang Zhang","doi":"10.1128/spectrum.01752-25","DOIUrl":"https://doi.org/10.1128/spectrum.01752-25","url":null,"abstract":"","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0175225"},"PeriodicalIF":3.8,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Description of high-altitude, cold-adaptive, metabolically versatile <i>Dyadobacter aurulentus</i> sp. nov. isolated from Western Himalayan farmland soils.","authors":"Amit Yadav, Kiran Kirdat, Vipool Thorat, Ngangyola Tuikhar, Kirti Chundawat, Tushar Lodha, Bhavesh Tiwarekar, Umera Patwekar, Malad Mubarak, Shuchi Shastri, Saurabh Kumar, Yogesh Shouche, Reeta Goel","doi":"10.1128/spectrum.01145-25","DOIUrl":"https://doi.org/10.1128/spectrum.01145-25","url":null,"abstract":"&lt;p&gt;&lt;p&gt;A novel bacterial strain, designated UC10&lt;sup&gt;T&lt;/sup&gt;, was isolated from cold, high-altitude farmland soil in the Gangotri region of the Western Himalayas, India. The strain is Gram-stain-negative, aerobic, non-spore forming, and non-motile, forming golden colonies that produce a flexirubin-like pigment. Strain UC10&lt;sup&gt;T&lt;/sup&gt; grows over a broad range of temperatures (5°C-30°C), pH (6-11), and salinities (up to 4% NaCl), with optimal growth at 30°C, pH 7.0, and 1% NaCl. The nearly full-length 16S rRNA gene sequence (MK743979) shares 98.95% similarity with &lt;i&gt;Dyadobacter luticola&lt;/i&gt;, followed by 97.68% with &lt;i&gt;Dyadobacter crusticola&lt;/i&gt; and 97.40% with &lt;i&gt;Dyadobacter koreensis&lt;/i&gt;, and phylogenetic analysis places UC10ᵀ in a distinct clade within the genus &lt;i&gt;Dyadobacter&lt;/i&gt;. Whole-genome phylogenetic analyses revealed that UC10&lt;sup&gt;T&lt;/sup&gt; is closely related to &lt;i&gt;Dyadobacter linearis&lt;/i&gt;, &lt;i&gt;D. crusticola&lt;/i&gt;, and &lt;i&gt;D. luticola&lt;/i&gt; but is clearly distinguished from them by low average nucleotide identity (&lt;81%), digital DNA-DNA hybridization (&lt;24%), and amino acid identity (&lt;80%) values. The genome of UC10&lt;sup&gt;T&lt;/sup&gt; is 6.93 Mb with a G+C content of 46.5 mol% and encodes multiple cold adaptation-related genes, including cold-shock proteins and fatty acid desaturases. The strain also harbors genes for aromatic compound degradation and demonstrated the ability to grow in minimal medium containing sodium benzoate as the sole carbon source. Additionally, fatty acid and polar lipid profiles of UC10&lt;sup&gt;T&lt;/sup&gt; revealed unique compositions, further supporting its differentiation. The combined genomic, phenotypic, and chemotaxonomic evidence supports the designation of strain UC10&lt;sup&gt;T&lt;/sup&gt; as representing a novel species, for which the name &lt;i&gt;Dyadobacter aurulentus&lt;/i&gt; sp. nov. is proposed. The type strain is UC10&lt;sup&gt;T&lt;/sup&gt; (= MCC 4019&lt;sup&gt;T&lt;/sup&gt; = KCTC 72455&lt;sup&gt;T&lt;/sup&gt; = JCM 34514&lt;sup&gt;T&lt;/sup&gt;).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;High-altitude, cold habitats such as the Gangotri region of the Western Himalayas remain underexplored for culturable microbial diversity. Here, we describe &lt;i&gt;Dyadobacter aurulentus&lt;/i&gt; sp. nov., a novel cold-adapted species isolated from such an environment. This strain demonstrates unique ecological and metabolic traits, including growth at low temperatures and degradation of aromatic compounds like sodium benzoate. Genomic analysis revealed key cold adaptation features such as cold-shock proteins, fatty acid desaturases, nitrate assimilation pathways, and multidrug resistance genes, supporting survival in nutrient-limited, low-temperature soils. The strain's distinct chemotaxonomic profile, marked by elevated C&lt;sub&gt;16:0&lt;/sub&gt; and unique polar lipids, underscores its ecological specialization. Together, these features point to its potential utility in bioremediation and cold-environment biotechnology. This study broadens our understanding of the adaptive strategies and ecological functions of &lt;i&gt;Dyadobacte","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0114525"},"PeriodicalIF":3.8,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TUBB1 promoter methylation is a promising biomarker for predicting HBeAg seroconversion in chronic hepatitis B.","authors":"Tong Zhao, Yuna Tang, Yu Sun, Jihui Li, Yuchen Fan, Chao Cui, Shuai Gao, Kai Wang","doi":"10.1128/spectrum.01344-25","DOIUrl":"https://doi.org/10.1128/spectrum.01344-25","url":null,"abstract":"<p><p>The identification of predictive indices for hepatitis B e antigen seroconversion (HBeAg SC) in patients with chronic hepatitis B (CHB) remains a challenge. We aimed to investigate whether the TUBB1 promoter methylation in peripheral blood mononuclear cells (PBMCs) can predict HBeAg SC. A total of 271 participants were recruited, comprising 145 patients with HBeAg-positive CHB, 94 with HBeAg-negative CHB, and 32 healthy controls (HCs). The patients with HBeAg-positive CHB were followed up for 72 weeks. The TUBB1 promoter methylation and the corresponding mRNA levels in PBMCs were detected using MethyLight and quantitative real-time PCR, respectively. The methylation levels of the TUBB1 promoter were remarkably elevated in patients with positive HBeAg, in comparison to those with negative HBeAg and HCs. Conversely, the relative mRNA expression levels of TUBB1 were significantly downregulated in patients with positive HBeAg, when compared to those with negative HBeAg and HCs. The TUBB1 promoter methylation levels showed a gradual decrease across the four phases of CHB. Patients with HBeAg SC had lower baseline methylation levels of the TUBB1 promoter than those without HBeAg SC. The TUBB1 promoter methylation was an independent predictor of HBeAg SC (odds ratio [OR] = 0.683, 95% CI 0.553-0.845, <i>P</i> < 0.001). The methylation of the TUBB1 promoter showed good predictive value for HBeAg SC in patients with positive HBeAg (area under the curve [AUC] = 0.805, 95% CI 0.704-0.907, <i>P</i> < 0.001). The methylation level of the TUBB1 promoter might be a potent biomarker for predicting HBeAg SC.</p><p><strong>Importance: </strong>Previous studies emphasized hepatitis B e antigen seroconversion (HBeAg SC) as a milestone for chronic hepatitis B (CHB) remission associated with reduced disease progression risks. While the significance of HBeAg SC is widely recognized, reliable non-invasive predictors for achieving this endpoint remain limited. Additionally, in our previous studies, DNA methylation of key regulatory genes has been linked to CHB progression. However, the association between TUBB1 promoter methylation and HBeAg SC, as well as its potential as a biomarker for clinical application, has not been fully elucidated. We demonstrated that TUBB1 promoter methylation levels were significantly higher in HBeAg-positive patients and that decreased methylation levels were independently associated with subsequent HBeAg SC during a 72-week follow-up. Our findings underscore the potential clinical utility of TUBB1 promoter methylation as a non-invasive biomarker for predicting HBeAg SC. This study provides strong evidence supporting the role of TUBB1 promoter methylation in predicting HBeAg SC, offering a novel biomarker for monitoring CHB.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0134425"},"PeriodicalIF":3.8,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated multi-omics identifies dysregulated lipid metabolism of paresis in dairy sheep during the early transition period.","authors":"Shuai Jiao, Fei Li, Tianxi Zhang, Guojie Yang, Ronghui Lu, Fadi Li, Long Guo, Zhiyuan Ma, Pengshan Zhao, Baocang Liu","doi":"10.1128/spectrum.01544-25","DOIUrl":"https://doi.org/10.1128/spectrum.01544-25","url":null,"abstract":"<p><p>Paresis during the early transition period is a prevalent metabolic disorder in prolific dairy sheep, characterized by a complex and poorly understood pathogenesis. This study longitudinally monitored a cohort of dairy sheep from 21 days antepartum to 1 day postpartum. During this period, blood, fecal, and colostrum samples were collected. The pathway of paresis was revealed by plasma metabolome and fecal 16S sequencing, and potential early biomarkers were identified. The physiological parameters of healthy dairy sheep (HDS) and paretic dairy sheep (PDS) differed in both the antepartum (not yet paresis) and postpartum (paresis) periods. Elemental analysis revealed higher levels of copper, potassium, and magnesium in PDS colostrum compared to HDS. Metabolomic analysis of HDS and PDS in antepartum identified 37 differential metabolites, with acylcarnitines (3-hydroxyhexadecadienoylcarnitine and 3-hydroxyoctanedioylcarnitine) emerging as promising early diagnostic biomarkers. 16S rRNA sequencing revealed distinct microbial signatures, with genera such as <i>Fusobacterium</i> and <i>Erysipelatoclostridium</i> enriched in PDS, whereas <i>Faecalibacterium</i> and <i>Bacillus</i> were more abundant in HDS. Integration of multi-omics data in postpartum revealed differences in glycerophospholipid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, glycine, serine and threonine metabolism, and primary bile acid biosynthesis between PDS and HDS. Our findings suggest that periparturient paresis in dairy sheep is linked to abnormal lipid and amino acid metabolism, with early potential biomarkers such as acylcarnitines identified. This study provides critical insights for developing strategies to prevent and manage periparturient paresis through targeted nutritional interventions and disease control.IMPORTANCEThis study investigates paresis in dairy sheep during the early transition period, identifying metabolic and physiological markers for early diagnosis. Longitudinal monitoring revealed prepartum differences in glucolipid profiles, liver enzymes, and oxidative stress markers between healthy and paretic sheep. Metabolomics identified 37 antepartum differential metabolites, including acylcarnitines, as potential biomarkers. Gut microbiota analysis revealed genera such as <i>Fusobacterium</i> and <i>Erysipelatoclostridium</i> enriched in paretic sheep, and <i>Faecalibacterium</i> and <i>Bacillus</i> in healthy individuals. Postnatal integration of multi-omics data revealed that paresis is closely associated with lipid metabolism and amino acid metabolism in dairy sheep. These findings support targeted nutritional strategies to mitigate periparturient metabolic disorders, enhancing dairy sheep health and productivity.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":" ","pages":"e0154425"},"PeriodicalIF":3.8,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}