mBio最新文献

{"title":"Nonlinear response of soil microfauna network complexity and stability to multilevel warming in an old-growth subtropical forest.","authors":"Debao Li, Yan Li, Haibian Xu, Jianping Wu","doi":"10.1128/mbio.00156-25","DOIUrl":"10.1128/mbio.00156-25","url":null,"abstract":"<p><p>The influence of climate warming on soil microbes and the mechanisms underlying these effects have become the subject of intense focus in microbial ecology and climate change research. However, it is largely unknown how warming affects soil microfauna network complexity and stability or how warming-induced changes may affect ecosystem functioning in old-growth forests. Here, we conducted a 3-year multilevel warming experiment in an old-growth subtropical forest using infrared heating with five treatments: ambient soil temperature and 0.8°C, 1.5°C, 3.0°C, and 4.2°C above ambient soil temperature. We found that soil microfauna network complexity and stability and multinutrient cycling were significantly higher under warming and showed similar hump-shaped trends across rising temperatures. The nonlinear responses of soil microfauna network complexity and stability were primarily linked to soil temperature, moisture, organic carbon, and microbial biomass. Importantly, we found that soil multinutrient cycling was positively influenced by microfauna network complexity and stability. Consequently, our findings provide insights into the key role of soil microfauna network structure in regulating soil multinutrient cycling, highlighting the need to consider soil organisms' potential interactions and that it is crucial to preserve soil microfauna \"interactions\" for ecosystem management in forests under global change.IMPORTANCEIt is largely unknown how warming affects soil microfauna network complexity and stability or how warming-induced changes may affect ecosystem functioning in old-growth forests. We conducted a 3-year multilevel warming experiment in an old-growth subtropical forest using infrared heating. We found that soil microfauna network complexity and stability were significantly higher under warming treatments and displayed nonlinear responses to different warming levels. Soil multinutrient cycling was positively and significantly influenced by microfauna network complexity and stability. Given that complex interconnections between soil microfauna are critical for sustaining ecosystem functioning, protecting microfauna \"interactions\" may be critical to mitigating the adverse impacts of warming-induced biodiversity reduction on ecosystem functioning.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0015625"},"PeriodicalIF":4.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prophage-encoded virulence factor, Gp05, contributes to endothelial cell dysfunction and immune evasion to promote persistent methicillin-resistant <i>Staphylococcus aureus</i> endovascular infections.","authors":"Yi Li, Adhar C Manna, Sarah Ibrahim, Richard A Proctor, Ambrose L Cheung, Yan Q Xiong","doi":"10.1128/mbio.01685-25","DOIUrl":"10.1128/mbio.01685-25","url":null,"abstract":"<p><p>Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) is a leading cause of endovascular infections, where interactions with endothelial cells play a critical role in pathogenesis. Gp05, a prophage-encoded protein, has previously been implicated in promoting antibiotic persistence by modulating MRSA cellular physiology and evading neutrophil-mediated killing. In this study, we investigated the role of Gp05 in MRSA-endothelial cell interactions, focusing on its impact on bacterial adhesion, invasion, cytotoxicity, and the host inflammatory response. Using an isogenic MRSA strain set-including a clinical persistent bacteremia isolate (PB 300-169), a <i>gp05</i> deletion mutant, and a <i>gp05</i>-complemented strain-we found that deletion of <i>gp05</i> significantly impaired MRSA invasion, intracellular survival, and damage toward endothelial cells. Notably, endothelial cells infected with the <i>gp05</i> deletion mutant induced a heightened endothelial inflammatory response, characterized by increased production of cytokines (IL-1β, TNF-α, IFN-γ, and CCL2/MCAF) and upregulated expression of inflammatory- and adhesion-associated molecules (VEGF, VCAM-1, TLR2, and TLR6). Furthermore, treatment of endothelial cells with purified Gp05 protein alone was sufficient to suppress endothelial inflammatory signaling and induce cytotoxic effects, suggesting that Gp05 exerts both intracellular and extracellular functions: intracellularly, by attenuating host immune activation to promote bacterial survival, and extracellularly, by directly disrupting endothelial barrier integrity and dampening immune recognition. In conclusion, Gp05 is a key virulence factor that contributes to MRSA persistence in endovascular infections by promoting endothelial cell dysfunction, suppressing host immune response, and enhancing bacterial survival. These findings highlight Gp05 as a potential therapeutic agent for disrupting MRSA pathogenesis in vascular tissues.</p><p><strong>Importance: </strong>This study reveals the critical role of Gp05, a prophage-encoded protein, in promoting antibiotic persistence during MRSA endovascular infections by modulating endothelial cell responses. By demonstrating that Gp05 enhances <i>S. aureus</i> endothelial cell invasion, intracellular survival, and cytotoxicity, while simultaneously suppressing host immune signaling, the research highlights Gp05 as a dual-function factor with both intracellular and extracellular effects on MRSA-host endothelial cell interactions. The identification of Gp05's capacity to disrupt endothelial cells and dampen host immune system advances our understanding of the mechanism of MRSA persistence. Given the clinical challenges of treating persistent MRSA infections, especially in endovascular contexts, these findings position Gp05 as a compelling target for novel therapeutic strategies.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0168525"},"PeriodicalIF":4.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12506005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The HIV-1 envelope cytoplasmic tail protects infected cells from ADCC by downregulating CD4.","authors":"Alexandra Tauzin, Étienne Bélanger, Jérémie Prévost, Halima Medjahed, Catherine Bourassa, Frederic Bibollet-Ruche, Jonathan Richard, Beatrice H Hahn, Andrés Finzi","doi":"10.1128/mbio.01763-25","DOIUrl":"10.1128/mbio.01763-25","url":null,"abstract":"<p><p>HIV-1-mediated CD4 downregulation is a well-known mechanism that protects infected cells from antibody-dependent cellular cytotoxicity (ADCC). While CD4 downregulation by HIV-1 Nef and Vpu proteins has been extensively studied, the contribution of the HIV-1 envelope glycoprotein (Env) in this mechanism is less understood. While Env is known to retain CD4 in the endoplasmic reticulum (ER) through its CD4-binding site (CD4bs), little is known about the mechanisms underlying this process. Here, we show that the cytoplasmic tail of Env is a major determinant in CD4 downregulation. This function is highly conserved as it was observed with nine different infectious molecular clones from four clades. The small but significant accumulation of CD4 at the surface of cells infected with Env cytoplasmic tail-deleted viruses is sufficient to trigger Env to adopt a more \"open\" conformation. This prompted recognition of HIV-1-infected cells by plasma from people living with HIV (PLWH) and several families of CD4-induced (CD4i) antibodies, leading to the elimination of these cells by ADCC. While cytoplasmic tail truncations are known to enhance Env expression at the cell surface, this did not fully explain the increased recognition of infected cells by CD4i antibodies and plasma from PLWH. Introduction of the CD4bs D368R mutation, which abrogates CD4 interaction, decreased Env recognition and ADCC. Overall, our results show that CD4 downregulation by the cytoplasmic tail of Env contributes to the protection of infected cells from ADCC.IMPORTANCEHIV-1-mediated CD4 downregulation is a central mechanism involved in the protection of infected cells from antibody-dependent cellular cytotoxicity (ADCC). CD4 downregulation prevents the premature interaction between HIV-1 envelope glycoproteins (Env) and CD4, which would otherwise \"open\" Env and expose vulnerable epitopes recognized by CD4-induced antibodies present in the plasma from people living with HIV. While the mechanisms of CD4 downregulation by the viral accessory proteins Nef and Vpu have been elucidated, the function of Env in this process is less clear. Here, we show that the cytoplasmic tail of Env plays an important role, thus contributing to the protection of infected cells from ADCC.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0176325"},"PeriodicalIF":4.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epistasis at the cell surface: what is the role of Erg3 loss-of-function in acquired echinocandin resistance?","authors":"Hans Carolus, Judith Díaz-García, Vladislav Biriukov, Stef Jacobs, Dimitrios Sofras, Alicia Pageau, Celia Lobo Romero, Lore Vinken, Pilar Escribano, Jesús Guinea, Katrien Lagrou, Christian R Landry, Toni Gabaldón, Patrick Van Dijck","doi":"10.1128/mbio.01419-25","DOIUrl":"10.1128/mbio.01419-25","url":null,"abstract":"<p><p>Echinocandins, which target the fungal β-1,3-glucan synthase (Fks), are essential for treating invasive fungal infections, yet resistance is increasingly reported. While resistance typically arises through mutations in Fks hotspots, emerging evidence suggests a contributing role of changes in membrane sterol composition due to <i>ERG3</i> mutations. Here, we present a clinical case of <i>Nakaseomyces glabratus</i> (<i>Candida glabrata</i>) in which combined mutations in <i>ERG3</i> and <i>FKS2</i>, but not <i>FKS2</i> alone, appear to confer echinocandin resistance. Integrated analyses reveal a recurrent association between Erg3 loss-of-function and echinocandin resistance mediated by Fks variation across <i>Candida</i> species, but exclude Erg3 loss-of-function as an independent resistance mechanism. Advances in Fks structural biology and insights into echinocandin-Fks interactions support a model of epistatic cross-talk between membrane sterols and Fks function. Understanding this interaction is crucial, as it may underlie not only acquired echinocandin resistance but also the broader development of multidrug resistance across major antifungal drug classes.IMPORTANCEA clinical case in which the combination of variation in a β‑1,3‑glucan synthase-encoding gene (<i>FKS2</i>) and the sterol desaturase-encoding gene <i>ERG3</i> seems to underlie echinocandin resistance, prompted us to hypothesize that membrane sterol changes may modulate, rather than independently cause, Fks‑linked resistance. We were able to explore this hypothesis due to recent developments in the field, such as the release of the FungAMR database, which enables global co‑occurrence analyses; AI‑driven variant effect predictors such as Evolutionary Scale Modeling (ESM) that can explore the impact of thousands of <i>ERG3</i> alleles; the cryo‑EM resolution of the Fks1 protein; and the first mechanistic model of echinocandin‑Fks1 binding. Together, these advances provide the structural and computational framework needed to delineate our hypothesis that specific sterol variants might influence β‑1,3‑glucan synthase function and drug binding. Further surveillance of this potentially epistatic interaction can be of significant clinical importance amid rising multidrug‑resistant infections, as overlooking such interactions could lead to under‑calling resistance and misguided therapy.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0141925"},"PeriodicalIF":4.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Picornavirus 3D polymerase inhibits antiviral innate immunity by blocking the activation of JAK-STAT signaling pathway.","authors":"Kangli Li, Xiangle Zhang, Chen Liu, Guoliang Zhu, Shuo Wang, Dandan Dong, Xiaodan Wen, Weijun Chao, Baohong Liu, Ruoqing Mao, Yi Ru, Hong Tian, Huanan Liu, Bo Yang, Jijun He, Jianhong Guo, Jianye Dai, Fan Yang, Zixiang Zhu, Haixue Zheng","doi":"10.1128/mbio.01666-25","DOIUrl":"10.1128/mbio.01666-25","url":null,"abstract":"<p><p>Picornaviruses are known for their rapid replication rate, which is a key characteristic that allows them to quickly infect host cells and produce progeny viruses. The interactions with host cells established by the virus to bypass host defense are essential for their rapid replication. The 3D protein, identified as the RNA-dependent RNA polymerase (RdRp) of picornaviruses, is central to viral replication. In this study, we delineated a conserved strategy employed by picornavirus 3D proteins to counteract the antiviral response elicited by interferons. Senecavirus A (SVA) 3D protein targets and hijacks JAK1, a pivotal component of the innate immune cascade, thereby decreasing the expression of a spectrum of interferon-stimulated antiviral genes. The interaction between the N-terminal region of SVA 3D (amino acids 1-152) and the FERM domain of JAK1 is responsible for the suppression of JAK-STAT signaling. Mechanistically, SVA 3D recruits the E3 ubiquitin ligase RNF125, inducing the K48-linked polyubiquitination of JAK1 at K205 and K249, which ultimately leads to the proteasomal degradation of JAK1. 3D proteins from other picornaviruses (FMDV, EMCV, and EV71) also suppress JAK1-mediated antiviral response. Collectively, these findings elucidate the suppressive regulatory mechanisms of picornaviruses 3D, highlighting a prevalent immune evasion tactic among picornaviruses, which will provide insights for developing antiviral strategies against picornaviruses.IMPORTANCEPicornaviruses can establish interactions with host cells to bypass host defense mechanisms. The highly conserved viral polymerase 3D protein of picornavirus broadly inhibited JAK-STAT signaling and promoted viral replication. Specifically, SVA 3D induces the K48-linked ubiquitination of JAK1 through recruitment of the E3 ubiquitin ligase RNF125. Similarly, FMDV, EMCV, and EV71 3D proteins act as negative regulators to inhibit JAK-STAT pathway activation. These findings unveil a common immune suppression strategy employed by picornaviruses, thereby advancing our understanding of picornavirus pathogenesis and opening avenues for developing antiviral strategies against picornaviruses.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0166625"},"PeriodicalIF":4.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12506094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptional responses of mouse proximal colon and colonoids during early whipworm infection.","authors":"Hyeim Jung, Joseph F Urban, Bruce A Rosa, Makedonka Mitreva","doi":"10.1128/mbio.02176-25","DOIUrl":"10.1128/mbio.02176-25","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Trichuriasis, caused by the parasitic nematode &lt;i&gt;Trichuris trichiura&lt;/i&gt;, affects 429-508 million people worldwide. Although the early phase of whipworm infection is crucial for establishing infection, its underlying molecular mechanisms remain unclear. In this study, we examined and compared host transcriptional responses during early infection of the mouse whipworm, &lt;i&gt;T. muris&lt;/i&gt;, using first-stage larvae (L1) in proximal colons from &lt;i&gt;in vivo&lt;/i&gt; models (B6 and STAT6-deficient mice) and &lt;i&gt;in vitro&lt;/i&gt; colonoid models. Differentially expressed genes and functional enrichment analysis revealed that while the \"neurotransmitter release\" pathway was uniquely upregulated in B6 mice, the \"lipid metabolism\" pathway was commonly modulated in both mice and colonoids, which may have implications for intestinal epithelial function during infection. Enrichment of alternative splicing (AS) events in splicing-related pathways across all models highlighted the need for further investigation into AS regulation mechanisms and its functional roles during early infection. Temporal transcriptomic profiling of L1 &lt;i&gt;T. muris&lt;/i&gt; in colonoids identified six clusters representing fundamental molecular pathways associated with parasite development and adaptation. Utilizing dual-RNA sequencing from infected colonoids, we conducted host-parasite co-expression analysis, identifying correlated gene pairs, including a negative correlation between &lt;i&gt;T. muris&lt;/i&gt;-secreted serine proteases and mouse genes involved in metabolism and epithelial cell functions. These findings provide valuable insights into the dynamic transcriptional regulation during early L1 &lt;i&gt;T. muris&lt;/i&gt; infection &lt;i&gt;in vivo&lt;/i&gt; and &lt;i&gt;in vitro&lt;/i&gt;, offering a resource for comparative studies in whipworm infection models. In conclusion, this comparative study serves as a starting point for deeper investigation into molecular mechanisms underlying early whipworm infection and opens up new opportunities for exploring host-parasite interactions.IMPORTANCETrichuriasis, caused by the parasitic nematode &lt;i&gt;Trichuris trichiura&lt;/i&gt;, remains a major public health concern, particularly in resource-limited regions. Current anthelmintics show suboptimal efficacy against whipworm infections, highlighting the critical need for novel therapeutic strategies. This study provides a comparative framework by integrating transcriptional profiles from &lt;i&gt;in vivo&lt;/i&gt; and &lt;i&gt;in vitro&lt;/i&gt; models during the early infection phase of &lt;i&gt;T. muris&lt;/i&gt;, a mouse model for &lt;i&gt;T. trichiura&lt;/i&gt;. Through this approach, we demonstrate the potential of proximal colonoids as a model for investigating key aspects of host-parasite interactions, including epithelial invasion and transcriptional dynamics, during early &lt;i&gt;T. muris&lt;/i&gt; infection. By employing dual-RNA sequencing, we not only characterize temporal gene expression dynamics of first-stage larvae but also identify host-parasite co-expression profiles, thereby shedding light on","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0217625"},"PeriodicalIF":4.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PARP14 is an interferon-induced host factor that promotes IFN production and affects the replication of multiple viruses.","authors":"Srivatsan Parthasarathy, Pradtahna Saenjamsai, Hongping Hao, Anna Ferkul, Jessica J Pfannenstiel, Daniel S Bejan, Yating Chen, Ellen L Suder, Nancy Schwarting, Masanori Aikawa, Elke Muhlberger, Adam J Hume, Robin C Orozco, Christopher S Sullivan, Michael S Cohen, David J Davido, Anthony R Fehr","doi":"10.1128/mbio.02299-25","DOIUrl":"10.1128/mbio.02299-25","url":null,"abstract":"<p><p>PARP14 is a 203 kDa multi-domain protein that is primarily known as an ADP-ribosyltransferase and is involved in a variety of cellular functions, including DNA damage, microglial activation, inflammation, and cancer progression. In addition, PARP14 is upregulated by interferon (IFN), indicating a role in the antiviral response. Furthermore, PARP14 has evolved under positive selection, again indicating that it is involved in host-pathogen conflict. We found that PARP14 is required for increased IFN-I production in response to coronavirus infection lacking ADP-ribosylhydrolase (ARH) activity and poly(I:C); however, whether it has a direct antiviral function remains unclear. Here, we demonstrate that the catalytic activity of PARP14 enhances IFN-β and IFN-γ responses and independently restricts ARH-deficient murine hepatitis virus (MHV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication. To determine if PARP14's antiviral functions extended beyond CoVs, we tested the ability of herpes simplex virus 1 (HSV-1), a DNA virus, vesicular stomatitis virus (VSV), a negative-sense RNA virus, and lymphocytic choriomeningitis virus (LCMV), an ambisense RNA virus, to infect A549 PARP14 knockout (KO) cells. While LCMV infection was unaffected, HSV-1 replication was increased in PARP14 KO cells, and VSV replication was decreased. These results indicate that PARP14 restricts HSV-1 replication but enhances the replication of VSV. A PARP14 active site inhibitor had no impact on HSV-1 or VSV replication, indicating that its effect on these viruses was independent of its catalytic activity. These data demonstrate that PARP14 promotes IFN production and has both proviral and antiviral functions targeting multiple viruses.IMPORTANCEThe antiviral response is largely regulated by post-translational modifications (PTM), including ADP-ribosylation. PARP14 is an ADP-ribosyltransferase that is upregulated by interferon and is under positive selection, indicating that it is involved in host-pathogen conflict. However, no anti-viral function has been described for PARP14. Here, we found that PARP14 represses both coronavirus and herpes simplex virus 1 (HSV-1) replication, demonstrating that PARP14 has antiviral functions. Surprisingly, we also found that PARP14 has pro-viral functions, as it was critical for the efficient replication of vesicular stomatitis virus (VSV). These data indicate that PARP14 has both proviral and antiviral functions. Defining the mechanisms used by PARP14 to both repress and promote virus replication will provide new insights into how PARPs regulate virus infection. .</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0229925"},"PeriodicalIF":4.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acetic acid produced by <i>Staphylococcus epidermidis</i> remodels chromatin architecture and suppresses gene expression in <i>Malassezia restricta</i>.","authors":"Jae Min Lee, Hyun Oh Yang, Hideki Tanizawa, Ken-Ichi Noma, Tae Kwon Lee, Won Hee Jung, Yong-Joon Cho, Kyoung-Dong Kim","doi":"10.1128/mbio.01592-25","DOIUrl":"10.1128/mbio.01592-25","url":null,"abstract":"&lt;p&gt;&lt;p&gt;The skin microbiome is composed of diverse microbial communities that engage in interkingdom interactions, influencing host physiology and microbial balance. Although &lt;i&gt;Malassezia restricta&lt;/i&gt; and &lt;i&gt;Staphylococcus epidermidis&lt;/i&gt; are codominant members of the human skin microbiome, the molecular mechanisms underlying their interactions remain poorly understood. We aimed to investigate the mechanism by which &lt;i&gt;S. epidermidis&lt;/i&gt;-derived acetic acid affects chromatin organization and gene expression in &lt;i&gt;M. restricta. S. epidermidis&lt;/i&gt; modulated chromatin structure and transcriptional activity in &lt;i&gt;M. restricta&lt;/i&gt; by secreting acetic acid (AcOH), a common skin-associated organic acid. Using &lt;i&gt;in situ&lt;/i&gt; Hi-C, we established the first three-dimensional genome architecture map of &lt;i&gt;M. restricta&lt;/i&gt; and identified putative centromeric loci based on inter-chromosomal association scores. Co-culture with &lt;i&gt;S. epidermidis&lt;/i&gt; or direct treatment with AcOH induced large-scale chromatin decompaction and enhanced centromeric clustering, indicating significant reorganization of the nuclear architecture. Through chromatin immunoprecipitation (ChIP)-seq analysis, we observed that AcOH exposure led to a redistribution of histone acetylation from promoter regions to gene bodies. This chromatin remodeling was further associated with extensive transcriptional repression, particularly of genes involved in translation, metabolism, and virulence, as revealed by RNA-seq analysis. Of note, these changes were specific to AcOH and were not replicated under inorganic acid stress (HCl), indicating a metabolite-specific epigenetic response. This study reveals a novel form of interkingdom communication in the skin microbiome, in which &lt;i&gt;S. epidermidis&lt;/i&gt;-derived AcOH acts as an epigenetic modulator in &lt;i&gt;M. restricta&lt;/i&gt;. Our findings provide key mechanistic insights into how bacterial metabolites influence fungal chromatin architecture and transcription, with implications for microbial community dynamics and skin health.IMPORTANCEThis study provides essential insights into interkingdom interactions within the human skin microbiome, highlighting how microbial metabolites influence fungal biology at the chromatin level. Specifically, we identify acetic acid (AcOH), secreted by &lt;i&gt;Staphylococcus epidermidis&lt;/i&gt;, as a key regulator that induces significant chromatin remodeling and transcriptional changes in &lt;i&gt;Malassezia restricta&lt;/i&gt;. By presenting the first three-dimensional genome architecture map of &lt;i&gt;M. restricta&lt;/i&gt;, our findings uncover metabolite-specific chromatin dynamics that cannot be replicated by inorganic acid stress. Additionally, the conservation of this chromatin response in other &lt;i&gt;Malassezia&lt;/i&gt; species suggests broader implications for understanding microbial adaptation mechanisms in the skin environment. This work underscores the critical role of bacterial metabolites as modulators of microbial interactions and provides new avenues for","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0159225"},"PeriodicalIF":4.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recurring acquisition of carbapenemase genes and global emergence of <i>Pseudomonas aeruginosa</i> ST-1047, a lineage shaped by geopolitical conflicts.","authors":"Ting L Luo, Brendan T Jones, Henry Dao, Viacheslav Kondratiuk, Valentyn Kovalchuk, Nadiia Fomina, Frieder Fuchs, Denis K Byarugaba, Fred Wabwire-Mangeni, Hannah Kibuuka, Jason R Smedberg, Ana C Ong, Yoon I Kwak, Antoni P A Hendrickx, Jason W Bennett, Francois Lebreton, Patrick T McGann","doi":"10.1128/mbio.02020-25","DOIUrl":"https://doi.org/10.1128/mbio.02020-25","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;i&gt;Pseudomonas aeruginosa&lt;/i&gt; sequence type (ST)-1047 is emerging globally as a carbapenemase-rich lineage, yet its evolutionary history and population structure are not known. Here, we performed a comprehensive genomic and epidemiological investigation of 141 ST-1047 isolates from 15 countries, integrating short- and long-read sequencing data with Bayesian phylogenetics and mobile genetic element analyses. Two clonal subpopulations were identified. Subclone 1, defined by &lt;i&gt;bla&lt;/i&gt;&lt;sub&gt;VIM-11&lt;/sub&gt; carriage and loss of &lt;i&gt;exoU&lt;/i&gt;, is proposed to have been imported to the United States following the medical evacuation of wounded service members from Afghanistan in 2005 and later seeded a nosocomial outbreak in Washington state. Subclone 2, carrying &lt;i&gt;bla&lt;/i&gt;&lt;sub&gt;IMP-1&lt;/sub&gt;, is undergoing rapid clonal expansion due to nosocomial outbreaks in Ukraine hospitals where infection control is impaired by the war with Russia. Genomic islands resembling &lt;i&gt;P. aeruginosa&lt;/i&gt; genomic island-97B mediated &lt;i&gt;bla&lt;/i&gt;&lt;sub&gt;IMP-1&lt;/sub&gt; duplication and integration at multiple chromosomal sites, including between iron-regulated small RNAs PrrF1 and PrrF2. Outside these subclones, independent acquisitions of &lt;i&gt;bla&lt;/i&gt;&lt;sub&gt;NDM-1&lt;/sub&gt; and/or &lt;i&gt;bla&lt;/i&gt;&lt;sub&gt;DIM-1&lt;/sub&gt; occurred via diverse resistance islands. While plasmids were detected in some ST-1047 isolates, chromosomal integration of carbapenemase genes has promoted stability and driven the population structure. This global study reveals that, since its emergence in the late 19th century, the ST-1047 lineage showed an exceptional ability to acquire diverse carbapenemases, and that geopolitical conflicts influenced its global spread on at least two occasions. These findings underscore the need for sustained global surveillance and high-resolution genomic analyses to prevent further spread of this high-risk pathogen.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Carbapenemase-producing &lt;i&gt;Pseudomonas aeruginosa&lt;/i&gt; is a major cause of healthcare-associated infections worldwide and is associated with high mortality due to limited treatment options. In this study, we characterize the emergence and international spread of a previously underrecognized lineage of &lt;i&gt;P. aeruginosa&lt;/i&gt; that has independently acquired and stabilized multiple resistance genes, including those encoding VIM, IMP, NDM, and Dutch imipenemase carbapenemases. Using genomic sequencing and evolutionary analyses, we show how this lineage emerged in the late 19th century and has since adapted by integrating resistance genes directly into its chromosome, promoting long-term stability and outbreak potential. Strikingly, we link its global expansion to population movements, soldier evacuations, and healthcare disruptions during armed conflicts in Afghanistan and Ukraine. This work reveals how political instability can drive the spread of multidrug-resistant bacteria and underscores the value of high-resolution surveillance to detect and contain emerging ","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0202025"},"PeriodicalIF":4.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251858","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":"Propolis improves intestinal barrier function against <i>Cryptosporidium parvum</i> via NLRP6 inflammasome.","authors":"Chang Xu, Qing He, Ziye Zhu, Kun Li","doi":"10.1128/mbio.02317-25","DOIUrl":"https://doi.org/10.1128/mbio.02317-25","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Cryptosporidiosis, a significant global zoonotic disease, poses a serious health threat due to the current lack of effective and specific therapeutic agents, particularly for immunocompromised individuals and young animals. The therapeutic potential and underlying mechanisms of propolis alcohol extract (BP) and water extract (WBP) in &lt;i&gt;Cryptosporidium parvum&lt;/i&gt; infection remain incompletely understood. The study assessed the cytotoxicity of BP and WBP, as well as their effects on host cell infection. For the &lt;i&gt;in vivo&lt;/i&gt; phase, an immunosuppressed mouse model was employed. Fecal oocyst shedding was quantified via RT-qPCR, and therapeutic efficacy was further evaluated through intestinal histopathological examination. Serum levels of inflammatory cytokines (IL-6, IL-1β, TNF-α, IL-10) and oxidative stress markers (MDA, SOD, GSH-Px) were measured using an enzyme-linked immunosorbent assay to assess immunomodulatory and antioxidant activities. In addition, the expression of intestinal tight junction proteins (ZO-1, occludin, claudin-1) and key components of the NLRP6/caspase-1/IL-18 inflammatory pathway was analyzed by RT-qPCR and Western blot. Molecular docking analysis predicted interactions between major bioactive compounds in propolis, such as hesperidin and quercetin, and the critical adhesion protein gp40/15 of &lt;i&gt;C. parvum&lt;/i&gt;. 16S rRNA sequencing revealed alterations in the intestinal microbiota, identifying key genera such as &lt;i&gt;Turicibacter&lt;/i&gt; and &lt;i&gt;Ligilactobacillus&lt;/i&gt;. Overall, the results of this study provide an important practical basis for the development of new anti-&lt;i&gt;C&lt;/i&gt;. &lt;i&gt;parvum&lt;/i&gt; drugs. Both BP and WBP significantly reduce &lt;i&gt;C. parvum&lt;/i&gt; infection burden, alleviate intestinal inflammation, reduce oxidative stress, and restore intestinal barrier integrity, with BP exhibiting more pronounced antiparasitic and immunomodulatory effects.IMPORTANCE&lt;i&gt;Cryptosporidium&lt;/i&gt; is an important pathogen that causes diarrhea in infants and young children and serious diseases in patients with weakened immune function. Currently, there are no specific drugs for its treatment. This study compared the inhibitory effects of propolis extracted by different methods on &lt;i&gt;Cryptosporidium&lt;/i&gt; and revealed its inhibitory mechanism. Propolis can directly target the key virulence factor gp40/15 protein on the surface of insects, interfering with the invasion and colonization of &lt;i&gt;C. parvum&lt;/i&gt;. In addition, propolis enhances the anti-&lt;i&gt;C&lt;/i&gt;. &lt;i&gt;parvum&lt;/i&gt; immune response by activating the host's NLRP6 inflammatome pathway and promoting the production of protective cytokines such as IL-18/IFN-γ. Studies have confirmed that propolis can simultaneously improve intestinal barrier damage and flora imbalance caused by infection. These findings provide a scientific basis for the development of propolis as a natural anti-&lt;i&gt;C&lt;/i&gt;. &lt;i&gt;parvum&lt;/i&gt; drug. The gp40/15 target and the NLRP6 inflammasome regulatory mechanism also offer new ideas for ","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0231725"},"PeriodicalIF":4.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251876","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}