mBio最新文献

{"title":"Cross-linking mass spectrometry guided structure prediction of disordered <i>Encephalitozoon hellem</i> proteins.","authors":"Elizabeth Weyer, Yongliang Wang, Tadakimi Tomita, Carlos Madrid-Aliste, Prithviraj Nandigrami, Andras Fiser, Simone Sidoli, Jennifer T Aguilan, Bing Han, Louis M Weiss","doi":"10.1128/mbio.02261-26","DOIUrl":"https://doi.org/10.1128/mbio.02261-26","url":null,"abstract":"<p><p>Microsporidia such as <i>Encephalitozoon hellem</i> are obligate intracellular human parasites that remain genetically intractable, limiting the functional characterization of their proteomes. Experimental structural studies are challenging, as many proteins in microsporidia comprise a large percentage of disordered regions. Computational structural studies based on homology-based modeling and the use of deep-learning algorithms for microsporidian proteins also remain limited because most have little to no sequence similarity to proteins with solved structures. To address these limitations, we developed an approach that incorporates cross-linking mass spectrometry (XL-MS) data into structure prediction. XL-MS data provide upper-bound distance constraints that can be incorporated into protein deep-learning-based modeling and subsequent docking. Using this approach, we generated a model of two interacting <i>E. hellem</i> spore wall proteins, spore wall protein 1B (Swp1b) and endospore protein 1 (EnP1), which have no clear homologs outside of microsporidia and contain several disordered regions. These proteins are abundant spore wall proteins of microsporidia and previously were not known to interact with one another. The resulting model not only is consistent with the experimental cross-links used to generate the model but was also subsequently confirmed by independently generated XL-MS data. The described AlphaLink-Modeller framework for structure prediction is particularly well suited to proteins with limited homology and/or substantial flexible regions, given that they adopt a defined structural state within a biological context, thereby extending integrative modeling approaches to previously inaccessible targets.</p><p><strong>Importance: </strong>In this article, we demonstrate an improved method for the prediction of the structure of protein complexes with no clear homologs and a considerable number of disordered regions. This is significant because these types of proteins are critical to understanding the biology of organisms, yet model generation of these classes has been inaccessible. The method incorporates experimental data obtained from cross-linking mass spectrometry (XL-MS) into the modeling process, providing a method to integrate such experimental data into computational modeling of the structure of proteins and protein interactions. For this paper, we have used this method for predicting the structure of two highly abundant <i>Encephalitozoon hellem</i> proteins in the spore wall that are important for host cell infection due to this pathogen of humans and other vertebrates.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0226126"},"PeriodicalIF":5.4,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228185","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":"Host-like temperature unlocks glucose uptake and metabolism in pathogenic <i>Leptospira</i>.","authors":"Ryo Ozuru, Michinobu Yoshimura, Deborah A Powers, Takumi Sonoda, Jason A Papin, Fumiko Obata, Glynis L Kolling, Kenji Hiromatsu","doi":"10.1128/mbio.01814-26","DOIUrl":"https://doi.org/10.1128/mbio.01814-26","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Pathogenic &lt;i&gt;Leptospira&lt;/i&gt; transitions between environmental reservoirs and mammalian hosts, exposing the bacterium to distinct temperature conditions. Although &lt;i&gt;Leptospira&lt;/i&gt; is generally considered to rely primarily on long-chain fatty acids for growth and to have limited capacity to use glucose, whether host-like temperature alters glucose-associated metabolic capacity remains unclear. Here, we used transcriptome-integrated genome-scale metabolic modeling to examine temperature-dependent metabolic states in pathogenic &lt;i&gt;Leptospira&lt;/i&gt;. Models contextualized with transcriptomic data from cultures at 37°C predicted increased flux through glucose transport, glucose phosphorylation, and downstream glucose-associated reactions than it did at 29-30°C. Similar temperature-dependent predictions were obtained for another pathogenic &lt;i&gt;Leptospira&lt;/i&gt; species under &lt;i&gt;in vitro&lt;/i&gt; conditions. Consistent with these findings, analysis of leptospires cultivated intraperitoneally in dialysis membrane chambers also predicted enhanced glucose uptake and metabolism under host-temperature conditions. &lt;i&gt;In vitro&lt;/i&gt; validation experiments showed increased bacterial uptake or accumulation of a fluorescent glucose analog, elevated expression of candidate glucose transporter genes, and glucose-dependent enhancement of bacterial growth at 37°C. Treatment with a glucose degradation pathway inhibitor, 2-deoxy-d-glucose, further supported a contribution of glucose-associated processes to proliferation at 37°C. Together, these findings indicate that pathogenic &lt;i&gt;Leptospira&lt;/i&gt; displays condition-dependent glucose uptake and glucose-associated metabolic activity that become apparent at host-like temperature, as opposed to being glucose-incompetent at environmental-like temperature. This prediction-driven framework refines the conventional view of &lt;i&gt;Leptospira&lt;/i&gt; carbon metabolism and provides a basis for future studies of glucose-associated metabolic capacity during mammalian infection.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Environmental reservoirs play a central role in the transmission of many bacterial pathogens, yet the metabolic mechanisms that enable adaptation to both environmental and host-associated niches remain largely unknown. Using a prediction-driven framework that combines contextualized genome-scale metabolic modeling with multi-omics analyses and experimental validation, we discovered that pathogenic &lt;i&gt;Leptospira&lt;/i&gt; activates glucose uptake and metabolism only under host-like conditions. This finding resolves a long-standing misconception arising from studies performed under conventional laboratory conditions and fundamentally revises our understanding of &lt;i&gt;Leptospira&lt;/i&gt; physiology. More importantly, our study establishes an integrative systems biology strategy for uncovering condition-dependent metabolic traits that would be difficult to identify experimentally alone, with broad applicability to diverse environmentally transmitted pathog","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0181426"},"PeriodicalIF":5.4,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228255","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":"mGem: Innate immune sensing of HIV-1 transcription in myeloid cells-a tale of two transcription start sites.","authors":"Ivy K Hughes, Suryaram Gummuluru","doi":"10.1128/mbio.03340-25","DOIUrl":"https://doi.org/10.1128/mbio.03340-25","url":null,"abstract":"<p><p>Suppressive antiretroviral therapy (ART) in people with HIV (PWH) arrests progression to AIDS and onward viral transmission. However, viral transcription from integrated HIV-1 proviruses persists on treatment and is linked to markers of chronic immune activation, contributing to the accelerated development of comorbidities in PWH. Of particular interest are persistent responses in long-lived tissue-resident myeloid cells, which direct tissue-level inflammatory processes through cytokine secretion and interactions with other immune cell populations. Here, we review recent findings on viral nucleic acid sensing events in HIV-infected myeloid cells to shed light on possible mechanisms of persistent inflammation resulting from chronic HIV-1 transcription in myeloid cells in PWH.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0334025"},"PeriodicalIF":5.4,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228209","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":"A novel mycovirus identified in clinical isolates of <i>Cryptococcus neoformans</i>.","authors":"Mysha N Turk, Abberly E Dela Rosa, J T Graham Solomons, Virginia E Glazier","doi":"10.1128/mbio.02060-26","DOIUrl":"https://doi.org/10.1128/mbio.02060-26","url":null,"abstract":"<p><p>Mycoviruses are widespread throughout the fungal kingdom and are known to infect diverse fungal taxa, including fungal species that are important plant and human pathogens. Although many mycoviruses have been found to have minimal effects on their host, several viruses have been found to modulate fungal physiology, and, as a result, impact fungal virulence. Screens for mycoviruses in clinically relevant fungi have identified numerous mycoviruses within several important human pathogens, but mycoviruses remain uncharacterized in the clinically relevant human pathogen <i>Cryptococcus neoformans. C. neoformans</i> is an opportunistic encapsulated yeast responsible for life-threatening cryptococcal meningitis, a leading cause of mortality among immunocompromised individuals, particularly those with HIV/AIDS. We performed a search for viral RNA-dependent RNA polymerase (RdRP) signatures in publicly available <i>C. neoformans</i> transcriptomic data. This search identified <i>Totiviridae</i> viral genomes within six clinical isolates of <i>C. neoformans</i> from Botswana. All six isolates originated from the cerebrospinal fluid (CSF) of HIV-positive individuals with cryptococcal meningitis. Reverse transcription PCR (RT-PCR) independently validated the continued presence of the virus in three of these clinical isolates. Subsequent analysis of the viral genome identified two genotypes of a single species of Totivirus. This new species possesses canonical features of the <i>Totiviridae</i> family, including a slippery heptamer and a predicted RNA pseudoknot structure involved in programmed -1 ribosomal frameshifting for RdRP expression. Taken together, these results provide evidence of a mycovirus capable of infecting <i>C. neoformans</i>.IMPORTANCEWe report the identification of a mycovirus capable of infecting <i>Cryptococcus neoformans</i>. While mycoviruses inhabit diverse fungal taxa, they have previously remained uncharacterized in this clinically significant fungal pathogen. The identification of the mycoviruses within <i>C. neoformans</i> isolated from the cerebrospinal fluid of individuals with cryptococcal meningitis places emphasis on the potential role of mycoviruses in the pathogenesis of <i>C. neoformans</i>.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0206026"},"PeriodicalIF":5.4,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220235","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":"Seasonal and evolutionary patterns of planktonic Hikarchaeia reveal ecological niches of marine rare biosphere constituents.","authors":"Fabian Wittmers, Nicole R Dames, Michelle Michelsen, Rachele Spezzano, Jacqueline Comstock, Kristin Bergauer, Kevin Vergin, Shuting Liu, Rachel Parsons, Ben Temperton, Mak A Saito, Craig A Carlson, Alexandra Z Worden","doi":"10.1128/mbio.01753-26","DOIUrl":"https://doi.org/10.1128/mbio.01753-26","url":null,"abstract":"<p><p>Members of Marine Group IV, now termed Hikarchaeia, hold an important transitional evolutionary position among Archaea but remain uncultivated, and their ecology remains uncharacterized. Over a 5-year period, we performed monthly profile sampling in the North Atlantic Subtropical Gyre and sequenced V4 16S rRNA gene amplicons, while also collecting additional size-fractionated and metagenomic samples. Hikarchaeal relative abundance annually peaked at ~1% of prokaryotic amplicons. Their relative abundances were significantly higher after deep winter mixing when thermal stratification isolated exported dissolved organic matter in the twilight zone (TZ), the boundary region between the epipelagic and mesopelagic. A diminutive 1.17 Mbp complete hikarchaeal genome was recovered by sequencing and co-assembling diel TZ metagenomes from 200 m during summer, where their relative abundances were highest. Phylogenomic reconstruction incorporating our new metagenome-assembled genome (MAG) and public MAGs established five clades. Clades I and III were in subtropical and tropical environments, with vertical partitioning: Clade I dominated the TZ, and Clade III detection initiated in the lower mesopelagic and extended into the bathypelagic. Clade V is polar-associated. Data sparsity makes Clade II and IV distributions unclear. All Hikarchaeia recovered thus far appear to be free-living aerobes capable of heterotrophy. Unlike MGI, MGII, and MGIII Archaea, and most marine pelagic bacteria, the Hikarchaeia encode bacterioruberin biosynthesis, except deep Clade III. Hikarchaeia also have nitrile hydratases alongside enzymes for carbon monoxide oxidation and menaquinone biosynthesis, suggesting previously unrecognized roles in nitrogen and carbon cycling. Collectively, our studies reveal niche partitioning of evolutionarily distinct uncultivated Hikarchaeia clades and patterning within the rare biosphere.IMPORTANCEThe ocean and its vertical water-column structure are changing with planetary warming; yet, there are many enigmatic microbes, especially those that inhabit the deep ocean. Here, we illuminate a group of uncultivated Archaea that were discovered over two decades ago but still lack clear distributions and habitat preferences. With the first complete hikarchaeal genome now in hand, we identified distinct lineages within the Hikarchaeia that occupy different marine niches. Strong reoccurring seasonal patterns were observed that closely followed the annual cycle of temperature-driven ocean stratification. Given rapid natural and anthropogenic perturbations at hand, establishing baselines for these Archaea is critical for improving our understanding and modeling of marine microbiomes and their biogeochemical functions.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0175326"},"PeriodicalIF":5.4,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220228","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":"Acetate modulates host physiology and bacterial energetics to improve antibiotic efficacy during obesity-associated infection.","authors":"Arsalan Hussain, Prateek Bhardwaj, Ashish Kumar Ray, Aakash Singh, Abhiroop Sett, Ranjana Pathania","doi":"10.1128/mbio.01630-26","DOIUrl":"https://doi.org/10.1128/mbio.01630-26","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Antibiotic efficacy is conventionally attributed to the susceptibility of the infecting pathogen. However, obese patients experience disproportionately poor infection outcomes despite receiving antibiotics to which pathogens remain genetically susceptible. These observations suggest that host-associated factors can influence treatment outcomes independently of the bacterial genotype, although the underlying mechanisms remain poorly understood. Using a mechanistic comparison of diet-induced obese and healthy mice infected with &lt;i&gt;Acinetobacter baumannii&lt;/i&gt;, we demonstrate that the effect of antibiotics is not solely a property of the pathogen but can be governed by a gut microbiota-derived metabolite acting on both host immunity and bacterial physiology. We identify obesity-associated acetate depletion as a key driver of antibiotic treatment failure, linking gut microbial metabolism to antibiotic activity during infection. We observed that this depletion impaired innate immune activation, reducing cytokine responses and neutrophil-mediated bacterial clearance. Under these conditions, &lt;i&gt;A. baumannii&lt;/i&gt; displayed enhanced tolerance to bactericidal antibiotics, particularly tobramycin. Given these findings, we investigated whether acetate could be leveraged therapeutically to restore antibiotic efficacy. We observed that oral acetate supplementation remodeled the dysbiotic microbiome, whereas systemic acetate restored innate immune competence and neutrophil-mediated bacterial clearance. Most importantly, acetate reversed antibiotic tolerance and restored aminoglycoside killing by directly sensitizing host-induced tolerant bacterial populations. Mechanistically, acetate directly reprogrammed bacterial physiology to enhance aminoglycoside-mediated killing. Combined acetate-tobramycin treatment resulted in eradication of tolerant populations and markedly improved bacterial clearance &lt;i&gt;in vivo&lt;/i&gt;. Our findings establish a mechanistic link between host metabolic state and antibiotic efficacy and identify acetate as a therapeutic intervention for obesity-associated gram-negative infections.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Antibiotic treatment failure in obese patients remains poorly understood and therapeutically unaddressed. This study reveals that host metabolic state can control antibiotic response through a gut microbiota-derived metabolite that acts on both host defense and bacterial physiology. We identify obesity-driven depletion of microbiota-derived acetate as a previously unrecognized determinant of antibiotic failure, operating independently of bacterial resistance. By simultaneously restoring gut microbial balance, rescuing impaired innate immunity, and directly sensitizing pathogens to aminoglycoside killing through bacterial membrane alteration, acetate supplementation addresses the host-pathogen-microbiome axis through a single intervention. Given its established clinical safety, acetate represents a compelling combination ther","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0163026"},"PeriodicalIF":5.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195189","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":"Diversity of dirammox microorganisms.","authors":"Gantuya Khasbaatar, Qun Han, Xiao-Kang Wang, Lei Song, Chang Liu, Xin Sun, Ze-Shen Liu, Ying Liu, Cheng-Ying Jiang, Ji-Guo Qiu, Shuang-Jiang Liu, Yanning Zheng, De-Feng Li","doi":"10.1128/mbio.01645-26","DOIUrl":"https://doi.org/10.1128/mbio.01645-26","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Our knowledge of the nitrogen cycle has been advanced by the discovery of anammox bacteria, ammonia-oxidizing archaea, and comammox bacteria, along with their high diversity. Direct ammonia oxidation (dirammox), a recently discovered heterotrophic nitrification pathway, converts ammonium and organic nitrogen directly to N&lt;sub&gt;2&lt;/sub&gt; through the DnfABC multienzyme system, further expanding our understanding of the nitrogen cycle. However, the taxonomic distribution, prevalence, and nitrogen metabolic potential of microorganisms encoding dirammox genes remain poorly understood. Here, large-scale genome mining identified complete &lt;i&gt;dnfABC&lt;/i&gt; gene clusters in 690 genomes representing 3 phyla and 26 genera. The &lt;i&gt;dnfABC&lt;/i&gt; cluster showed a striking bimodal prevalence: it was nearly ubiquitous in &lt;i&gt;Alcaligenes&lt;/i&gt;, &lt;i&gt;Delftia&lt;/i&gt;, and &lt;i&gt;Microvirgula&lt;/i&gt; but occurred sporadically in most other genera. These microorganisms were recovered from diverse environments, particularly organic nitrogen-rich habitats. Comparative analyses of DnfABC phylogeny, gene cluster organization, GC content, and flanking mobile genetic elements indicate that the &lt;i&gt;dnfABC&lt;/i&gt; cluster is conserved within several core genera, whereas its sporadic distribution in other lineages suggests that horizontal gene transfer may have contributed to its dissemination. The &lt;i&gt;dnfABC&lt;/i&gt; cluster co-occurs with genes associated with assimilatory nitrate/nitrite reduction to ammonium, dissimilatory nitrate/nitrite reduction to ammonium, denitrification, and/or nitrogen fixation, but not with marker genes for nitrification or anammox, indicating diverse nitrogen metabolic potential among potential dirammox microorganisms. Functional assays further showed that diverse &lt;i&gt;dnfABC&lt;/i&gt; clusters consistently conferred ammonium- and glutamine-oxidizing activities in &lt;i&gt;Escherichia coli&lt;/i&gt;, despite exhibiting low activities in their native hosts. These results suggest that dirammox is a broadly distributed, metabolically flexible, and tightly regulated pathway and may represent an overlooked route of nitrogen transformation in organic-rich habitats.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Nitrogen is essential for all life, and our understanding of the nitrogen cycle has advanced substantially with the discovery of anammox bacteria, ammonia-oxidizing archaea, and comammox bacteria, which exhibit remarkable taxonomic and metabolic diversity. This study suggests that the recently discovered dirammox pathway may be more widespread in nature than previously recognized. Potential dirammox microorganisms exhibit broad phylogenetic and ecological distributions, high genomic diversity, and notable metabolic versatility. Functional assays indicate that dirammox activity is tightly regulated in native hosts, suggesting that its ecological role depends on specific environmental conditions. Unlike canonical nitrification and anammox, dirammox operates under conditions where other nitrogen transformation","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0164526"},"PeriodicalIF":5.4,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195237","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":"Pre-existing systemic and nasal antibodies against avian H5 influenza A viruses vary according to childhood imprinting.","authors":"Peta Edler, Kevin J Selva, Ellie Reilly, Malet Aban, Ian G Barr, Jennifer A Juno, Adam K Wheatley, Amy W Chung, Stephen J Kent, David J Price, Marios Koutsakos","doi":"10.1128/mbio.01892-26","DOIUrl":"10.1128/mbio.01892-26","url":null,"abstract":"<p><p>Avian influenza A viruses (IAVs) pose a constant pandemic threat, with the recent 2.3.4.4b clade of the H5 subtype causing high pathogenicity and spreading across animal species and geographic locations. Understanding human pre-existing immunity to avian H5 IAV can inform on population susceptibility, a critical aspect of pandemic preparedness. To that end, we analyzed the IAV HA-specific antibodies across individuals born between 1928 and 1999 with different early life exposures to IAV subtypes. Individuals born prior to 1957 had the highest pre-existing serum antibodies to group 1 HA antigens, including the 2.3.4.4b H5 and a group 1 HA stem antigen. These birth year-specific patterns were not reflected in the limited pre-existing serum neutralizing antibodies detectable against a 2.3.4.4b H5 IAV or in H5-specific memory B cell populations. They were, however, evident in pre-existing nasal IgG and IgA titers to H5, which were greater in individuals born prior to 1957. Our findings demonstrate that the immunological biases afforded by early life exposure extend to antibodies detected in the nasal mucosa, the site of IAV replication.IMPORTANCEUnderstating pre-existing immunity to influenza A viruses (IAVs) of pandemic potential is an important aspect of pandemic preparedness. This includes an understanding of the heterogeneity of pre-existing immunity across the population. Here, we demonstrate that pre-existing antibodies to H5 IAV vary according to the year of birth and childhood imprinting. We demonstrate that this is the case for both systemic and nasal antibodies, highlighting the importance of understanding pre-existing mucosal immunity at the sites of influenza virus replication.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0189226"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148829768","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":"IL-1α protects intestinal barrier in murine visceral leishmaniasis.","authors":"Laís A Sacramento, Pedro Alexandre Sampaio, Gabriela Castilho Martins, Luciana Benevides, Claudia Gonzalez-Lombana, Gabrielle B Trindade, Michely Mello, Fernando Q Cunha, Livia S Zaramela, João S Silva, Phillip Scott, Vanessa Carregaro","doi":"10.1128/mbio.00657-26","DOIUrl":"10.1128/mbio.00657-26","url":null,"abstract":"<p><p>Interleukin-1 (IL-1) is a pleiotropic cytokine important in inflammatory and infectious diseases, but its roles in visceral leishmaniasis (VL) remain poorly understood. Here, we evaluated the role of IL-1 cytokines during experimental visceral leishmaniasis. We showed that IL-1 receptor 1 (IL-1R1) deficiency enhanced the gamma interferon (IFNγ)-mediated response and restricted parasites in an IL-1α-dependent manner, whereas IL-1β deficiency had no effect. The absence of IL-1R1 and IL-1α led to intestinal microbiota dysbiosis. The infection induced IL-1α expression in the gut. The absence of IL-1α led to reduced expression of tight-junction molecules, increased intestinal permeability, and bacterial translocation. These alterations amplified non-<i>Leishmania</i>-specific IFN-γ production, which was reversed by broad-spectrum antibiotic treatment. Bone marrow chimeric transplantation showed that hematopoietic cells are the source of IL-1α during VL. Together, our findings reveal that IL-1α acts as a key regulator of gut barrier integrity in VL and indirectly restrains systemic IFNγ-driven inflammation. This work highlights IL-1α-dependent intestinal protection as an overlooked component of VL pathogenesis.IMPORTANCEVisceral leishmaniasis (VL) is a systemic and chronic disease caused by <i>Leishmania</i> parasites. Most infected individuals remain asymptomatic due to an appropriate IFNγ-mediated response. By contrast, the disease progression is characterized by excessive inflammation, with high levels of cytokines, among them IFNγ. IL-1 cytokines play a role in modulating immune responses and epithelial barriers. We report that IL-1α protects the intestinal environment and indirectly regulates the IFNγ-mediated response during experimental VL. The infection induces IL-1α expression in the intestine, and its absence leads to dysbiosis, gut permeability, and bacterial translocation. Overall, this study reveals the role of IL-1α in intestinal integrity during VL and in regulating the IFNγ-mediated response. Expanding the knowledge of IL-1α in intestinal protection may support therapeutic approaches to improve the outcomes of infection.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0065726"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963520","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 catheterized urinary tract selects for <i>MRR1</i>-mediated efflux and fluconazole resistance in <i>Candida albicans</i> biofilms.","authors":"Shane A Cristy, Jennifer N Walker, Michael C Lorenz","doi":"10.1128/mbio.01785-26","DOIUrl":"10.1128/mbio.01785-26","url":null,"abstract":"<p><p>Catheter-associated urinary tract infections (CAUTIs) are the most common nosocomial infection in developed countries, and <i>Candida</i> species are among the most frequently isolated organisms. Despite this, little is known about the biology, host-pathogen interactions, or outcomes of these infections, and this has led to uncertain guidelines for clinical management of <i>Candida</i> CAUTIs. Here, we develop the first physiologically relevant artificial urine medium (AUM) that supports fungal growth in a manner similar to, but more consistent than, human urine samples. We demonstrate that human catheter-associated (CA) clinical isolates of <i>C. albicans</i> exhibit environment-dependent fluconazole resistance: many isolates determined to be susceptible by standard CLSI testing in RPMI (MIC ≤ 2 µg/mL) were fully resistant (MIC ≥ 128 µg/mL) when grown in pooled human urine or AUM, complicating clinical management, which is based on catheter exchange and fluconazole treatment. Transcriptomic profiling of biofilms formed in AUM revealed a remarkably convergent upregulation of efflux and detoxification processes across clinical isolates with diverse biofilm phenotypes. Whole-genome sequencing of the CA isolates identified variant alleles of transcriptional regulators of drug efflux, including <i>MRR1</i>, that have been previously associated with antifungal resistance. A competition assay confirmed that Mrr1 provides a fitness advantage in urine and AUM in a urea-dependent manner. Thus, we show that the urinary environment promotes a unique biofilm differentiation program and selects for adaptations that increase drug resistance and would be predicted to render standard treatment regimens ineffective.IMPORTANCECatheter-associated urinary tract infections are the most common nosocomial infection in the United States, and <i>Candida albicans</i> is one of the most frequently isolated organisms from these infections. Despite this high prevalence, few molecular studies have examined <i>C. albicans</i> biology in the urinary environment, and recommendations for clinical management lack robust evidence. Here, we show that clinical catheter-associated isolates of <i>C. albicans</i> identified as susceptible to fluconazole by standard clinical microbiology testing were resistant when grown in human or artificial urine. We identified transcriptional responses intrinsic to the urinary environment that produce this environment-specific resistance phenotype. Biofilm growth in the urinary environment induces cellular processes for efflux and detoxification. These findings suggest that standard susceptibility testing may not predict fluconazole efficacy in the urinary tract and underscore the need for niche-informed approaches to antifungal management of these common infections.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0178526"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963528","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}