Microbiological research最新文献

{"title":"Role of enniatins and deoxynivalenol in interspecific growth and competition in vitro among the principal causal agents of Fusarium head blight","authors":"Francesco Tini ,&nbsp;Giovanni Beccari ,&nbsp;Lorenzo Covarelli ,&nbsp;Nora A. Foroud ,&nbsp;Claudia Camplone ,&nbsp;Aurelie H. Benfield ,&nbsp;Donald M. Gardiner ,&nbsp;Linda J. Harris ,&nbsp;Michael Sulyok ,&nbsp;Roberto Romani ,&nbsp;Ilaria Bellezza ,&nbsp;Luisa Ederli","doi":"10.1016/j.micres.2025.128376","DOIUrl":"10.1016/j.micres.2025.128376","url":null,"abstract":"<div><div><em>Fusarium graminearum</em> and <em>Fusarium avenaceum</em>, causal agents of Fusarium head blight (FHB), are known to produce secondary metabolites such as deoxynivalenol (DON) and enniatins (ENNs), respectively. These species, along with other FHB pathogens, <em>Fusarium culmorum</em> and <em>Fusarium poae</em>, often co-exist in a single host-plant head, potentially resulting in the accumulation of different secondary metabolites. This study aimed to investigate the <em>in vitro</em> role of ENNs and DON in <em>Fusarium</em> development, metabolism and competition. The effects of three concentrations of enniatin B (ENB) and DON, alone or in combination, were assessed on the growth of <em>F. avenaceum</em>, <em>F. graminearum</em>, <em>F. poae</em>, and <em>F. culmorum</em> on potato dextrose agar (PDA). The expression of <em>F. graminearum</em> genes potentially related to stress response, growth and involved in trichothecene biosynthesis, was analyzed to elucidate the secondary metabolite action. The role of ENNs and DON in interspecific competition was explored through dual-culture experiments on PDA and rice flour agar (RFA) using mutant strains of <em>F. avenaceum</em> and <em>F. graminearum</em>. A combination of ENB and DON at the highest concentration (100 mg L⁻¹) had the most significant inhibitory effect on the growth of all tested species. Even at the lowest concentration (10 mg L⁻¹), ENB+DON significantly inhibited the growth of <em>F. graminearum</em> (5 %) and <em>F. avenaceum</em> (14 %). Gene expression analysis in <em>F. graminearum</em> revealed that exposure to 100 mg L⁻¹ of ENB, DON, or their combination induced a stress response. However, dual-culture experiments demonstrated that ENNs and DON did not play a role in the <em>in vitro</em> interactions between <em>F. graminearum</em> and <em>F. avenaceum</em>. The results obtained may prove useful in shedding light on the competitive dynamics among the various <em>Fusarium</em> species involved in causing FHB, and on how their secondary metabolites may play a role, either alone or in combination, in the development of the disease.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"303 ","pages":"Article 128376"},"PeriodicalIF":6.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145364921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pheromone MAPK pathway regulates the yeast-to-hypha transition in the parasitic mushroom Naematelia sinensis in a cell fusion–independent manner","authors":"Ying Yang ,&nbsp;Jiaqi Lu ,&nbsp;Caihong Dong","doi":"10.1016/j.micres.2025.128374","DOIUrl":"10.1016/j.micres.2025.128374","url":null,"abstract":"<div><div><em>Naematelia sinensis</em> (Jin Er), a distinctive parasitic mushroom, relies on its interaction with <em>Stereum hirsutum</em> for fruiting body formation. The transition from yeast to hyphae is essential for its lifecycle, facilitating both parasitism and sexual reproduction. Under axenic conditions, however, it predominantly exists in the yeast form. This study established conditions that induce yeast-to-hypha transition and explored the underlying regulatory mechanisms. Hyphal induction was successfully achieved using a medium derived from mushroom spent substrate, with lactose significantly enhancing the transition. Hyphal formation occurred in heterokaryons or co-cultured monokaryons with different <em>B</em> mating-type loci, underscoring the crucial role of the <em>B</em> mating locus. Notably, hyphal development was observed even without physical contact between monokaryons of different <em>B</em> mating loci, suggesting that cell fusion is not a prerequisite and a diffusible signal likely mediates the transition. Genome resequencing revealed structural variations and sequence divergence at the <em>B</em> locus in compatible strains. Transcriptomic analysis revealed the pheromone MAPK pathway as the regulator of the transition, alongside a unique lactose metabolic pathway that diverges from the classical <em>Kluyveromyces</em> model. Lactose appears to function both as a carbon source and as a possible signaling molecule driving dimorphism. These findings provide new insights into the mechanisms of fungal dimorphism and lay a foundation for future research on fruiting body formation and parasitism in <em>N. sinensis</em>.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"303 ","pages":"Article 128374"},"PeriodicalIF":6.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145323194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferroptosis for food safety: An innovative and sustainable strategy in pathogenic bacteria inactivation and antimicrobial resistance modulation","authors":"Xinyu Zhou ,&nbsp;Jun-Hu Cheng ,&nbsp;Xiao Yang ,&nbsp;Da-Wen Sun","doi":"10.1016/j.micres.2025.128360","DOIUrl":"10.1016/j.micres.2025.128360","url":null,"abstract":"<div><div>Microbial contamination in food has long posed a significant global public health challenge. The growing antibiotic resistance of foodborne pathogens, particularly multidrug-resistant bacteria, has diminished the effectiveness of traditional antibiotic treatments and increased the public health burden. There is an urgent need for innovative strategies to control foodborne pathogenic bacteria and their resistance. Since the discovery of ferroptosis, a regulatory modality of cell death, researchers have advanced our understanding of its mechanisms. While ferroptosis is primarily observed in eukaryotic cells, some studies indicate that microbial cells also undergo a similar process. This ferroptosis-like death depends on the Fenton reaction and is triggered by iron overload, leading to excessive reactive oxygen species (ROS) and lipid peroxidation. However, current knowledge on ferroptosis-mediated control of foodborne pathogenic bacteria and antimicrobial resistance remains limited. Ferroptosis is primarily triggered by excess intracellular ferrous ions (Fe²⁺) and disruptions in antioxidant systems. Several studies have utilized this feature to design antimicrobial experiments, which have been successfully applied to antimicrobial infection treatment. Additionally, ferroptosis affects antibiotic-resistant bacteria mainly by inducing direct lethal effects through iron-dependent lipid peroxidation, and disrupting iron homeostasis, which bypasses traditional resistance mechanisms and enhances antibiotic efficacy. This review aims to summarize the concepts, mechanisms, and regulatory measures of ferroptosis while discussing its application in controlling pathogenic bacteria. Further insights into the specific molecular mechanisms of ferroptosis in foodborne pathogenic bacteria are essential to enhance inactivation precision and modulate antimicrobial resistance, thereby facilitating its practical application in food safety.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"303 ","pages":"Article 128360"},"PeriodicalIF":6.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145459161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disarming Salmonella virulence with 32H-hilE anti-virulence bacteriophage","authors":"Jinwoo Kim ,&nbsp;Haejoon Park ,&nbsp;Young Hyun Jung ,&nbsp;Ho Jae Han ,&nbsp;Doyeon Kim ,&nbsp;Sangryeol Ryu ,&nbsp;Minsik Kim","doi":"10.1016/j.micres.2025.128396","DOIUrl":"10.1016/j.micres.2025.128396","url":null,"abstract":"<div><div>As the development of new antibiotics struggles with the continuous emergence of drug-resistant bacteria, targeting bacterial virulence factors instead of viability has been proposed as one of the alternative approaches to combat the pathogens. Here, we genetically engineered the temperate phage SPC32H to serve as a delivery vehicle for key negative regulators of <em>Salmonella</em> virulence to inhibit <em>Salmonella</em> infection. Negative regulator genes associated with <em>Salmonella</em> pathogenicity island 1 (SPI1), <em>hilE</em>, <em>csrA</em>, and <em>lrp</em>, were inserted into the phage SPC32H genome and expressed under a strong constitutive promoter. When <em>Salmonella</em> cells lysogenized by the engineered phages were exposed to the virulence-inducing condition, the expression of key positive regulators and major virulence factors associated with SPI1 was significantly reduced. Furthermore, in a murine early-intervention model, oral administration of the engineered phage 32H-<em>hilE</em> shortly after a lethal <em>Salmonella</em> challenge led to a significant increase in survival. No noticeable side effects were observed in mice treated with the engineered phage alone. These results suggest the relevance of the engineered phages that suppress the <em>Salmonella</em> virulence network as alternative anti-<em>Salmonella</em> agents without resistance concerns. This proof-of-concept study of anti-virulence phages could open a new avenue for controlling pathogenic bacteria using engineered temperate phages as vectors of anti-virulence factors.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"303 ","pages":"Article 128396"},"PeriodicalIF":6.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145517481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular responses of Aspergillus sydowii to growth at extreme chaotropic concentrations of MgCl2","authors":"Deborah González-Abradelo ,&nbsp;Lyselle Ruíz de León ,&nbsp;Reinier Gesto-Borroto ,&nbsp;Tonatiuh Moreno-Perlín ,&nbsp;Nilda del C. Sánchez-Castellanos ,&nbsp;Yordanis Pérez-Llano ,&nbsp;Juán Cabral-Miramontes ,&nbsp;Elva Aréchiga-Carbajal ,&nbsp;María del Rayo Sánchez-Carbente ,&nbsp;Cene Gostinčar ,&nbsp;Nina Gunde-Cimerman ,&nbsp;Ramón Alberto Batista-García","doi":"10.1016/j.micres.2025.128390","DOIUrl":"10.1016/j.micres.2025.128390","url":null,"abstract":"<div><div>Studies on microbial adaptations to salt stress, particularly in fungi, have focused mainly on high concentrations of NaCl. The effects of other inorganic salts on biological systems are much less well known. This study investigates the effects of MgCl₂ (0–2.0 M), a chaotropic salt, on the halophilic fungus <em>Aspergillus sydowii</em> (EXF-12860) and compares these results with those obtained with the kosmotropic NaCl. While <em>A. sydowii</em> thrived at MgCl₂ concentrations previously considered lethal (up to 2.0 M), differences in morphological, physiological, metabolic, and molecular responses were observed. At 0.5–1.0 M, growth rates were similar under both salts, but higher MgCl₂ concentrations (1.5–2.0 M) significantly inhibited growth, reduced hyphal elongation, and decreased cell density. During growth in the presence of NaCl, a wide range of carbon sources was utilized, but high MgCl₂ interfered with substrate metabolism and uncoupled growth from metabolic activity. Both salts induced the production of compatible solutes (glycerol, erythritol), with higher accumulation under MgCl₂. Oxidative stress responses were also stronger under MgCl₂, including increased catalase and glutathione peroxidase activity. Transcriptomic analyses revealed significant changes in gene expression under MgCl₂ stress, with upregulation of ion transport, cell wall remodelling, glycerol biosynthesis, and oxidative defense pathways. In contrast, NaCl triggered responses focused on osmotic balance and maintenance of cell integrity. These findings emphasize the need for a deeper investigation of microbial tolerance mechanisms in chaotropic environments.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"303 ","pages":"Article 128390"},"PeriodicalIF":6.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145557450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The hidden players: The mycobiome of pancreatic ductal adenocarcinoma tumors","authors":"Estrin Camille ,&nbsp;Bertout Sébastien,&nbsp;Bellet Virginie","doi":"10.1016/j.micres.2025.128392","DOIUrl":"10.1016/j.micres.2025.128392","url":null,"abstract":"<div><div>The microorganisms that inhabit the human body are known to play a role in human health and disease. Continuing to elucidate their specific role in disease progression is, however, necessary. The imbalance of these microorganisms–known as dysbiosis–has been linked to a myriad of intestinal diseases, and more recently to cancer. Despite making up less than 0.1 % of the human microbiome, dysbiosis of the fungal component of the microbiome—the mycobiome—has been found to contribute to the tumorigenesis and progression of certain types of tumors, pancreatic ductal adenocarcinoma (PDAC) included. The quantity and composition of the mycobiome was found to differ between healthy pancreatic tissue, the gut mycobiome of PDAC patients and PDAC tissue. Moreover, in a murine model of PDAC, it was shown that fungal ablation had a protective effect on tumor growth, and that specific fungal species, such as <em>Malassezia globosa</em>, contribute to tumor growth as well as to the inflammatory environment observed in PDAC tumors which promotes tumor progression. Research shows that fungal presence contributes to shaping the immune microenvironment through the activation of the complement system and/or by eliciting a type 2 immune response. Despite these preliminary findings, given the novelty of the field and of the bioinformatics pipelines used to analyze sequencing data, standardized approaches are still under development, thus leading to disagreement on the reliability of these results. The purpose of this review is to provide an up-to-date overview of the current research regarding the contribution of the fungal mycobiome in PDAC tumor progression and the overall tumor microenvironment (TME) of PDAC tumors.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"303 ","pages":"Article 128392"},"PeriodicalIF":6.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145466790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated metabolomic and transcriptomic analysis to elucidate the antifungal and antimycotoxin mechanisms of natural stilbenoids against Fusarium graminearum","authors":"Trang Tran-Minh ,&nbsp;Nadia Ponts ,&nbsp;Stéphane Bernillon ,&nbsp;Pierre Waffo-Téguo ,&nbsp;Caroline Rouger ,&nbsp;Florence Richard-Forget ,&nbsp;Vessela Atanasova","doi":"10.1016/j.micres.2025.128370","DOIUrl":"10.1016/j.micres.2025.128370","url":null,"abstract":"<div><div>Climate change is driving a rise in the contamination of crops by mycotoxins, threatening global food security. If agrochemical use is to be reduced, environmentally friendly antimycotoxin solutions are urgently needed. This study aims to elucidate the antifungal and antimycotoxin modes of action of stilbenoid molecules from vine by-product extracts against <em>Fusarium graminearum</em>, the primary causal agent of <em>Fusarium</em> head blight in wheat and a main producer of type B trichothecene (TCTB) mycotoxins. <em>E</em>-resveratrol (RES), a monomer, and <em>E</em>-vitisin B (VIT), a tetramer, were selected as the targeted stilbenoids due to their predominance in vine extracts. VIT (8 µM) showed greater efficacy than RES (35 µM) in inhibiting spore germination, biomass production, and TCTB yield. To better understand their modes of action, a multi-omics approach combining mRNA-seq-based transcriptomics and LC-MS/MS-based untargeted metabolomics was employed. mRNA-seq data evidenced that VIT exposure altered the expression of nearly half of <em>F. graminearum</em> genes, whereas RES induced only minimal transcriptomic changes. Integrated with metabolomics data, our findings suggest that VIT’s modes of action involves: (1) disruption of the fungal cell wall and plasma membrane via downregulation of sphingolipid metabolism, (2) inhibition of sporulation and hyphal growth, and (3) both direct and indirect interference with TCTB biosynthesis. These findings support the potential of viniculture waste-derived compounds as biofungicides, offering a dual benefit of reducing cereal mycotoxin contamination and valorising underused vine biomass.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"303 ","pages":"Article 128370"},"PeriodicalIF":6.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145355234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rhizosphere resilience: Exploring microbial diversity and metabolic responses in long-term eucalyptus plantations","authors":"Ning Li ,&nbsp;Yuemei Zhang ,&nbsp;Zhaolei Qu ,&nbsp;Jie Xu ,&nbsp;Angang Ming ,&nbsp;Hui Sun ,&nbsp;Lin Huang","doi":"10.1016/j.micres.2025.128381","DOIUrl":"10.1016/j.micres.2025.128381","url":null,"abstract":"<div><div>The large-scale cultivation of eucalyptus has led to significant ecological challenges, such as declines in soil microbial diversity and soil degradation. To address these issues, management practices incorporating nitrogen-fixing species and adjusted rotation periods have been proposed. However, their impacts on rhizosphere soil microorganisms and metabolites remain insufficiently understood. This study employed metagenomic and untargeted metabolomics techniques to investigate the response of rhizosphere microorganisms and metabolites in eucalyptus plantations under different management regimes: monoculture plantation, plantation mixed with a nitrogen-fixing tree species, monoculture second-generation plantation, and second-generation mixed plantation. The results revealed that mixed plantation increased microbial diversity compared to continuous cropping. In contrast, second-generation monoculture led to a loss of unique microbial species and reduced microbial community stability compared to the first-generation monoculture. In nutrient-poor pure second-generation plantations, the bacterium Gemmatimonadetes (relative abundance: PF: 0.13 %, PS: 0.39 %, MF: 0.14 %, MS: 0.21 %)—which plays a key role in soil phosphorus cycle—was enriched. Although continuous cropping improved the organic phosphorus mineralization function, it decreased the abundance of genes related to carbon (<em>rbcL</em> and <em>ppc</em>) and phosphorus cycle (<em>phoP</em> and <em>ppk2</em>). The metabolite fluocinolone is negatively correlated with carbon, nitrogen and phosphorus cycle gene components in our dataset, while echinocystic acid and bezitramide are positively correlated. These findings highlight that mixed plantations enhance the ecological niche of eucalyptus rhizosphere by altering the interaction between rhizosphere microbial composition, function, and host plant metabolism.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"303 ","pages":"Article 128381"},"PeriodicalIF":6.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145418898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting bacterial motility: Prospective therapeutic countermeasures","authors":"Yilin Sun ,&nbsp;Pengcheng Wang ,&nbsp;Yidan Chai ,&nbsp;Ru Song ,&nbsp;Ming Cheng ,&nbsp;Jingrrong Gao ,&nbsp;Luminita Duma ,&nbsp;Yannick Rossez ,&nbsp;Xiaoyu Zou ,&nbsp;Ye Tao ,&nbsp;Huicheng Yang","doi":"10.1016/j.micres.2025.128369","DOIUrl":"10.1016/j.micres.2025.128369","url":null,"abstract":"<div><div>Microorganisms have developed several motility types regulated by environmental conditions in host colonization to support transmission and virulence. Targeting motility is a promising antivirulence strategy. Herein, the current and developing countermeasures targeting filament-based and gliding/sliding motility mechanisms, including assembly, structure, and secretion, are reviewed. Additionally, indirect strategies that influence motility, including targeting c-di-GMP signaling, quorum sensing, and the two-component system, are described. Biological interference with metabolites and bacteriophage, as well as the promising strategies are also addressed in the review. The limitation and challenges of antimotility interventions are critically analysed. Overall, targeting motility represents a novel antivirulence paradigm to disarm pathogens while minimizing selective pressure for resistance, pointing to a promising direction for future combination therapies.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"303 ","pages":"Article 128369"},"PeriodicalIF":6.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145289927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meningitic Escherichia coli disrupts the blood-brain barrier through pyroptosis and tight junction degradation and NLRP6 deficiency aggravates infection outcomes","authors":"Kaixiang Jia ,&nbsp;Yangyang Du ,&nbsp;Xinrui Cao ,&nbsp;Xin Shen ,&nbsp;Jinrong Ran ,&nbsp;Yi Lu ,&nbsp;Lianci Peng ,&nbsp;Zhiwei Li ,&nbsp;Rendong Fang","doi":"10.1016/j.micres.2025.128388","DOIUrl":"10.1016/j.micres.2025.128388","url":null,"abstract":"<div><div>Extraintestinal pathogenic <em>Escherichia coli</em> (ExPEC) can cause meningitis by breaching the blood-brain barrier (BBB), but the underlying mechanisms remain unclear. In this study, we found that meningitic ExPEC disrupts the BBB through two distinct mechanisms: inducing endothelial pyroptotic cell death and disrupting tight junction (TJ) proteins. Transcriptomic analysis revealed activation of cell death pathways and suppression of tight junction signaling in ExPEC-stimulated human cerebral microvascular endothelial cells (hCMEC/D3). ExPEC infection induced pyroptotic cell death characterized by caspase-1 and GSDMD activation, along with inflammatory cytokine production. Additionally, ExPEC reduced TJ protein expression and disrupted their continuous distribution. Based on transcriptomic results showing simultaneous activation of NLR and TLR pathways, we investigated the role of NLRP6, a unique receptor with dual functions. Silencing NLRP6 in hCMECs exacerbated ExPEC-induced TJ protein disruption but reduced pyroptotic cell death. <em>In vivo</em> experiments indicated that NLRP6^-/- mice showed accelerated mortality, higher bacterial loads, more severe brain tissue damage, enhanced TJ protein disruption, and elevated inflammatory cytokines following ExPEC infection. Brain transcriptomic analysis revealed that NLRP6 deficiency resulted in impaired immune function, downregulation of tight junction pathways, and upregulation of neurological dysfunction-related pathways. These results demonstrate that meningitic ExPEC promotes bacterial meningitis through dual BBB disruption mechanisms, and NLRP6 plays a crucial protective role by maintaining BBB integrity during infection.</div></div>","PeriodicalId":18564,"journal":{"name":"Microbiological research","volume":"303 ","pages":"Article 128388"},"PeriodicalIF":6.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145466815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}