mSphere最新文献

{"title":"Endoplasmic reticulum stress reduces caspofungin resistance in <i>Cryptococcus neoformans</i>.","authors":"Xianya Qu, Guanggan Hu, Christopher W J Lee, Linda Horianopoulos, James W Kronstad","doi":"10.1128/msphere.00451-26","DOIUrl":"10.1128/msphere.00451-26","url":null,"abstract":"<p><p>Echinocandin antifungal drugs, such as caspofungin, inhibit β-1,3-glucan synthesis to impair cell wall formation. Caspofungin is effective in the clinic against <i>Aspergillus</i> and <i>Candida</i> species but ineffective against <i>Cryptococcus neoformans</i>, the fungus responsible for life-threatening meningoencephalitis in immunocompromised individuals. The mechanisms of caspofungin resistance in <i>C. neoformans</i> are associated with calcineurin signaling and functions that influence membrane and cell wall composition. The synergistic effects of caspofungin have been studied in combination with various inhibitors, but it is not known whether resistance can be overcome by agents that target the endoplasmic reticulum to influence protein glycosylation, as well as cell wall and membrane composition. Additionally, the role of the polysaccharide capsule of <i>C. neoformans</i> in blocking the access of caspofungin to the target Fks1 glucan synthase is not clear. Here, we identified a potential synergistic effect between caspofungin and the glycosylation inhibitor tunicamycin, with a significant reduction in proliferation, capsule attachment, and chitin and β-1,3-glucan levels when the drugs were used in combination. A targeted screen also identified other agents that influence ER function and that potentially display synergy with caspofungin. Overall, our analysis provides evidence that targeting the ER to impair cell wall and membrane integrity and capsule formation is an effective strategy to overcome caspofungin resistance in <i>C. neoformans</i>.IMPORTANCE<i>Cryptococcus neoformans</i> is the major cause of life-threatening meningoencephalitis in immunocompromised people. Unfortunately, the number of antifungal drugs available to treat cryptococcal disease is quite limited, and unlike other pathogenic fungi, <i>C. neoformans</i> is intrinsically resistant to the echinocandin group of drugs. These drugs target cell wall biosynthesis, and the mechanisms of cryptococcal resistance are not entirely clear. In this study, we demonstrate synergy between the echinocandin drug caspofungin and tunicamycin, an inhibitor of protein glycosylation in the endoplasmic reticulum. Combined treatment impacts cell wall and plasma membrane composition, thus providing insights into approaches to overcome resistance.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0045126"},"PeriodicalIF":4.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148892012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbiome symbiosis, host-pathogen dynamics, and the search for new therapeutics: highlights from the Theobald Smith Society Spring 2026 Symposium.","authors":"Rachana Rao Battaje, Kyle S Skalenko, Ahri Han, Kamilakhon Abdujabbarova, Jeffrey M Boyd, Valerie J Carabetta, Jason H Yang, Srujana S Yadavalli","doi":"10.1128/msphere.00366-26","DOIUrl":"10.1128/msphere.00366-26","url":null,"abstract":"<p><p>The annual Theobald Smith Society (TSS) spring meeting was convened at Rutgers University in New Brunswick, New Jersey, on 8 May 2026. TSS is the New Jersey branch of ASM and holds two annual meetings, in the fall and spring. These meetings bring together microbiologists, trainees at all levels, and professionals from both academia and industry to share their research, to network, and to engage in discussions on a wide array of topics that fall under ASM's three main units: health, mechanism discovery, and applied and environmental microbiology. The TSS spring meeting brought together more than 140 attendees from institutions across New Jersey. This report highlights the vision and work of TSS and ASM, the breadth of research presented at the meeting through invited talks and posters, and the two keynote lectures on nutritional immunity and the modern decline of human microbiome diversity.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0036626"},"PeriodicalIF":4.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148762286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced soil microbial diversity and altered co-occurrence networks associated with <i>Phytophthora nicotianae</i> infection in flue-cured tobacco fields.","authors":"Ayodeji Bello, Jing Yuan, Kamal Chhetri, Ran Yang, Jiayu Dong, Priyanka Gangwar, Ruizhu Shi, Zhenshan Chen, T David Reed, Ryan Stewart, Yiming Feng, Yuan Zeng","doi":"10.1128/msphere.00501-26","DOIUrl":"10.1128/msphere.00501-26","url":null,"abstract":"<p><p><i>Phytophthora nicotianae</i> is a persistent and highly destructive soilborne oomycete that causes black shank of tobacco and continues to threaten its production despite integrated management. Although soil microbiomes are increasingly recognized as important components of disease outcomes, little is known about how soil microbial communities vary with <i>P. nicotianae</i> DNA concentrations and black shank pressure under field conditions. We examined relationships among 17 soil physicochemical properties, microbial community features, <i>P. nicotianae</i> DNA levels, and black shank outcomes in three flue-cured tobacco fields sampled repeatedly throughout one growing season. <i>Phytophthora nicotianae</i> DNA concentrations were associated with several soil physicochemical properties. The field with the lowest disease pressure had higher microbial alpha diversity, the simplest bacterial network, and a moderately complex fungal network. In contrast, the field with the highest black shank mortality showed the lowest alpha diversity, the most complex bacterial network, and the least complex fungal network. Over the growing season, microbial alpha diversity declined, and disease outcomes were associated with field-specific shifts in microbial community composition. <i>Trichoderma</i>, <i>Fusarium</i>, and <i>Globodera</i> were most abundant in the high-disease field, whereas multiple bacterial groups within Firmicutes, Proteobacteria, and Actinobacteriota were negatively associated with <i>P. nicotianae</i> in the lower-disease fields. These results indicate that <i>P. nicotianae</i> DNA abundance and black shank pressure are associated with soil physicochemical properties and field-dependent patterns in microbial diversity, community composition, network topology, and several microbial taxa. Our study provides a field-based foundation for future research to experimentally test candidate microbial indicators and microbe-pathogen relationships relevant to black shank risk assessment.IMPORTANCEBlack shank is a persistent soilborne disease that threatens tobacco production and is difficult to manage because the pathogen survives in soil and disease outcomes vary from field to field. This study shows that measuring the pathogen alone may not fully explain disease risk. Across three Virginia tobacco fields, black shank pressure was linked to soil properties and differences in the soil microbial community. Fields with lower disease pressure had higher microbial diversity and different groups of bacteria associated with lower levels of <i>Phytophthora nicotianae</i>, the causal agent of black shank. These findings suggest that future disease-risk assessment may be improved by considering soil conditions and microbial indicators together with pathogen detection. The work provides a foundation for identifying soil and microbial features that could support more targeted and sustainable black shank management strategies.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0050126"},"PeriodicalIF":4.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Minimal organism JCVI-syn3.0, an engineered derivative of <i>Mycoplasma mycoides</i>, encodes an assortment of unrecognized membrane transporters and immunity factors.","authors":"Arcady R Mushegian, Phillip K Yamamoto, Naoki Torikai, Kazuharu Arakawa","doi":"10.1128/msphere.00077-26","DOIUrl":"10.1128/msphere.00077-26","url":null,"abstract":"<p><p>In 2016, researchers at the J. Craig Venter Institute produced JCVI-Syn3.0, a derivative of <i>Mycoplasma mycoides</i> subsp. <i>capri</i> Large Colony strain GM12 with a re-engineered, minimized genome. The minimal synthetic genome of 532 kbp encodes 473 genes, selected from ∼910 parent genes on the basis of their indispensability, that is, a lethal phenotype caused by a knockout of each such gene. Among these genes, 438 genes encode proteins, of which ∼150 were not assigned a molecular function or predicted cellular role. A decade later, despite community annotation efforts, 50-60 of these putative proteins still lack any assigned function. We analyzed the intrinsic sequence characteristics, evolutionary conservation, and three-dimensional AlphaFold models of this least understood subset of the JCVI-Syn3.0 genes. We predicted conserved sequence motifs and structural features and inferred molecular functions of six proteins likely involved in membrane transport or membrane interactions, and six proteins that apparently belong to bacterial immunity systems, such as putative antitoxins, an essential toxin-like protein, and a member of a previously unnoticed clade of Cas4-like nucleases. The spatial models produced for this challenging data set by the AlphaFold pipeline help dissect proteins into discrete domains, which are often more convenient to analyze by sequence similarity than whole proteins. In several cases, AlphaFold models also enable functional inference more directly, based on spatial matching of the models to the databases of known protein structures.IMPORTANCEThe smallest synthetic genome, JCVI-Syn3.0, encodes 438 proteins. JCVI-Syn3.0 was obtained by combining all genes whose deletion from a larger parental genome of <i>M. mycoides</i> subsp. <i>capri</i> Large Colony strain GM12 causes a complete stop or a significant delay in bacterial growth. Thus, nearly every protein in this minimal genome is essential; however, we do not know what ∼15% of these genes do. Using computational methods, we predicted molecular functions for about a quarter of these enigmatic proteins, including several proteins that are related to the components of recently discovered bacterial immunity systems.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0007726"},"PeriodicalIF":4.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uncovering the mechanism of action of a historical antimicrobial against <i>S. aureus</i> and <i>A. baumannii</i>.","authors":"Oluwatosin Qawiyy Orababa, Jessica Furner-Pardoe, Alexander Gale, Blessing Anonye, Joe Ratcliff, Natasha Reddy, Ramón Garcia Maset, Niamh E Harrington, Shajini Subhaskaran, Séamus Holden, Stephen P Diggle, Christophe Corre, Freya Harrison","doi":"10.1128/msphere.00494-26","DOIUrl":"10.1128/msphere.00494-26","url":null,"abstract":"<p><p>Natural products have provided most of our modern pharmacopeia, serving as active molecules or scaffolds for active molecules. Their use in drug development is often inspired by their traditional or historical medical use. For many decades, this discovery pipeline has focused on identifying a single molecule responsible for much of the biological activity of a \"raw\" natural product preparation (e.g., a whole-plant extract) and scoping this molecule for clinical potential. However, it is increasingly realized that historical/traditional remedies with significant biological activity may owe this activity to the combined action of multiple molecules. Concomitantly, microbiologists increasingly argue that effectively fighting antimicrobial-resistant infections will rely on combination therapies that combine multiple antimicrobials and/or adjuvant molecules. We previously reconstructed a complex historical remedy, Bald's eyesalve. Our reconstruction of this remedy had strong antibiofilm activity, which relied on the presence of multiple ingredients. Here, we report that Bald's eyesalve has multiple antibacterial effects on exemplar gram-positive (<i>Staphylococcus aureus</i>) and gram-negative (<i>Acinetobacter baumannii</i>) pathogens. Bald's eyesalve disrupts bacterial membrane integrity; inhibits the expression of genes associated with bacterial adhesins, virulence factors, and efflux pumps in both <i>S. aureus</i> and <i>A. baumannii</i>; inhibits quorum sensing in <i>S. aureus</i>; and causes the downregulation of genes involved in <i>de novo</i> nucleotide biosynthesis in <i>S. aureus</i>. Finally, we show that this multifaceted mechanism of action makes it difficult for <i>S. aureus</i>, <i>A. baumannii</i>, and <i>Pseudomonas aeruginosa</i> to evolve resistance against Bald's eyesalve. Bald's eyesalve could be used to identify a defined cocktail of natural products suitable for preclinical testing as a multi-target antibacterial preparation to which resistance may arise more slowly than current single-molecule antibiotics.IMPORTANCEThe increasing mortality and economic cost of antimicrobial resistance (AMR) have made it one of the biggest threats to global health. Available antibiotics are in short supply due to the slow progress in the discovery of new antibiotics. Hence, there is a need for alternative treatment options against difficult-to-treat infections. We have identified a natural product cocktail based on a historical remedy with broad-spectrum antibacterial activity and a multifaceted mechanism of action. We have shown that there is slower resistance evolution to this cocktail compared to mainline antibiotics, and it could be used as the foundation of an alternative treatment to antibiotics in clinical settings.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0049426"},"PeriodicalIF":4.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148888036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of inactivated and live attenuated, tetravalent dengue vaccine prime-boost strategies in a randomized, open-label, phase I study: implications for understanding immune correlates of protection.","authors":"Michael Koren, Simon Pollett, Keisha Akerele, Christine Lee, Kristin Mills, James E Moon, Paul B Keiser, Jack Hutter, Melinda Hamer, Justin M Curley, Nathanial K Copeland, Stephen J Thomas, Michael K McCracken, Jun Hang, Richard G Jarman, Jeffrey R Currier, Heather Friberg, Gregory D Gromowski","doi":"10.1128/msphere.00497-26","DOIUrl":"10.1128/msphere.00497-26","url":null,"abstract":"<p><p>Vaccines that elicit balanced, protective immunity to all four dengue virus (DENV) types are needed to reduce the global burden of dengue disease. Achieving this goal has been a challenge for dengue vaccine developers, particularly when immunizing dengue immunologically naïve individuals. In this randomized, phase I, open-label study of 40 healthy adults, we evaluated a heterologous, tetravalent purified inactivated vaccine (PIV) prime and a tetravalent live attenuated vaccine (LAV) boost. We compared a 0, 90 day PIV/LAV prime-boost schedule to a 0, 180 day schedule. These two PIV/LAV regimens elicited similar, high, and balanced cellular and humoral immune responses to DENV 1-4, although the condensed schedule was associated with more severe adverse events. In a subsequent clinical trial [K. E. Lyke, J. V. Chua, M. Koren, H. Friberg, et al., Lancet Infect Dis 24:896-908, 2024, https://doi.org/10.1016/S1473-3099(24)00100-2], the PIV/LAV vaccinees were challenged with DENV-1 and most were unprotected and experienced more pronounced dengue fever-like illness than unvaccinated controls. These outcomes underscore critical gaps in our understanding of mechanistic correlates of dengue vaccine-mediated protection and disease risk.</p><p><strong>Importance: </strong>Dengue vaccine research and development has been complicated by several factors, including an incomplete understanding of immunologic correlates of protection and immune-mediated risk of severe disease. High and balanced immunity elicited by the tetravalent purified inactivated vaccine (PIV)/live attenuated vaccine (LAV) prime-boost vaccine strategy was predicted to provide protection from dengue virus type 1 (DENV-1) challenge in a subsequent clinical study, but vaccinees were unprotected and had an unexpected increase in symptom severity compared to unvaccinated controls. Evidence of exposure to a specific DENV type by viral genome detection (e.g., by quantitative RT-PCR) in acute samples or measurement of post-exposure, type-specific antibody responses (e.g., by serum antibody depletion) are known correlates of protection. However, current methods of measuring type-specific antibody are not ideal for evaluating groups of vaccinees, even in relatively small clinical trials. Newer, high-throughput methods of determining DENV type-specific immune responses and discovery of other correlates of protection are needed to more reliably evaluate dengue vaccine candidates.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0049726"},"PeriodicalIF":4.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-psychotic drugs act synergistically in combination with antifungal drugs to inhibit drug-resistant <i>Cryptococcus neoformans</i> and <i>Candida albicans</i>.","authors":"Magali Ayala, Alifia Jakamartana, Rodrigo Mamede Dos Santos Costa, Eric Cheuk-Kiu Cheung, Joseph M Bednarek, Christian T Moreau, Jessica C S Brown","doi":"10.1128/msphere.00432-26","DOIUrl":"10.1128/msphere.00432-26","url":null,"abstract":"<p><p>Systemic fungal infections cause an estimated 3.8 million deaths annually, approximately 10% of which are caused by drug-resistant infections. With only five classes of antifungal drugs, treatment options are limited. Here, we explore synergistic drug combinations-when the efficacy of two drugs combined is greater than expected based on the sum of each individual drug's efficacy-to improve treatment of drug-resistant <i>Cryptococcus neoformans</i> and <i>Candida albicans</i>. Chlorpromazine acts synergistically with both amphotericin B and fluconazole against multiple fungal species, including azole-resistant <i>C. neoformans</i> and <i>C. albicans</i>. We then performed a genome-wide knockout mutant screen and found that ESCRT pathway mutants are resistant to chlorpromazine, while knockout mutants of genes involved in fatty acid biosynthesis are sensitive. Based on these data, we investigated sterol and fatty acid composition in chlorpromazine-treated cells and found only minor increases in sterol precursors, but a substantial increase in lipid droplet size and decreased lipid droplet numbers. This lipid droplet formation potentially sequesters lipid bioavailability and response to membrane stress. Together, these data suggest that chlorpromazine and its analogs are potentially promising treatments for systemic fungal infections that act via lipid homeostasis and stress response.</p><p><strong>Importance: </strong>Fungal infections are a large and expensive health burden with high mortality rates. People with compromised immune systems from cancer, solid organ transplant, HIV infection, and other conditions are particularly affected. Systemic fungal infections are difficult to treat because there are few available drugs and treatment periods last months or years. Long treatment times increase the risk of treatment failure and can contribute to the rise of resistance. We identified an additional class of drugs, chlorpromazine and other phenothiazine drugs, that amplify the activity of existing antifungal drugs amphotericin B (AmB) and fluconazole (FLZ). AmB and FLZ act by targeting ergosterol, the fungal equivalent of cholesterol, which is required for a functional plasma membrane. Chlorpromazine increases the formation of lipid drops, which sequester lipids such as ergosterol. When chlorpromazine is combined with AmB, the fungal cell cannot respond to the plasma membrane damage caused by AmB, inhibiting the fungal cells. This work identifies new target processes and drugs that could treat deadly fungal infections.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0043226"},"PeriodicalIF":4.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Location and habitat specificity structure benthic microbial assemblages in a temperate seagrass ecosystem.","authors":"Gabriel A Serrano, Alejandro De Santiago, Tiago J Pereira, Mirayana Marcelino Barros, Holly M Bik","doi":"10.1128/msphere.00431-26","DOIUrl":"10.1128/msphere.00431-26","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Seagrass meadows are globally distributed coastal ecosystems that provide habitats for diverse species and facilitate ecosystem services, such as carbon storage and nutrient cycling. However, anthropogenic activities and climate change are causing seagrass decline worldwide, broadly impacting ecosystem functioning. Although macrofaunal communities in seagrass habitats are relatively well studied, benthic microbial assemblages (including microeukaryote groups such as protists and microbial metazoa) remain underexplored. In this study, we used environmental DNA (eDNA) metabarcoding to characterize assemblages of bacteria/archaea (16S rRNA gene), microeukaryotes (18S rRNA amplified from raw sediment), and meiofauna (18S rRNA amplified from sieved and Ludoxed sediment fractions) in seagrass fields and bare sediment habitats at three sites along an estuarine gradient in Bodega Harbor, California. We found that microbial and microeukaryote communities were primarily structured by location, with sediment properties (sand vs silt/clay proportions) being the main driver of community assemblages. Habitat type was a secondary factor influencing benthic fauna, with bare sediments typically displaying higher biodiversity than seagrass beds, except at Westside Park mudflats, where bare sediments showed significantly reduced diversity compared to all other sampling locations. The differential recovery of nematode bioindicator taxa, including &lt;i&gt;Terschellingia&lt;/i&gt;, &lt;i&gt;Daptonema&lt;/i&gt;, &lt;i&gt;Viscosia&lt;/i&gt;, &lt;i&gt;Microlaimus&lt;/i&gt;, and &lt;i&gt;Spilophorella&lt;/i&gt;, suggested that abiotic factors, such as physical disturbance, pollution, or oxygen dynamics, may influence the success of specific taxa at each site. Finally, nematode-bacterial co-occurrence networks confirmed known symbiotic associations and suggest additional taxonomic relationships to explore in future studies. Our findings underscore the importance of environmental gradients and microhabitat features in shaping benthic biodiversity in temperate seagrass ecosystems.IMPORTANCESeagrass meadows, which sustain a wide variety of plant and animal life, are vital coastal habitats. These submerged ecosystems support biodiversity, coastal protection, biogeochemical cycling, and carbon storage. However, seagrass habitats worldwide are declining due to pressures from climate change and human activity. This study characterizes the microbial and microeukaryote communities (including microbial animals with a body size &lt;1 mm) that inhabit and surround temperate seagrass meadows in Bodega Harbor, California. Our findings demonstrate that location is a primary factor that determines microbial communities inhabiting sediments at each site, with habitat type (bare sediment vs seagrass beds) exerting a secondary influence on the biodiversity and distribution of microbial species. By using nematode bioindicator taxa and nematode-bacterial co-occurrence patterns, our results also suggest specific environmental factors that shape sedi","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0043126"},"PeriodicalIF":4.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Individual host variation in single-cell responses to enteroaggregative <i>Escherichia coli</i> infection modeled with human colon organoids.","authors":"Ling Qiu, Tajhal D Patel, Hannah E Jones, Cristian Coarfa, Anthony W Maresso","doi":"10.1128/msphere.00758-25","DOIUrl":"10.1128/msphere.00758-25","url":null,"abstract":"<p><p>Enteroaggregative <i>Escherichia coli</i> (EAEC) is a leading cause of diarrhea worldwide. Interestingly, EAEC disease outcomes vary dramatically among infected individuals, ranging from asymptomatic colonization to acute and chronic diarrhea. While previous research has focused on EAEC virulence factors, emerging evidence suggests that host genetic and cellular background may be equally important in determining disease susceptibility. To understand host-driven disease heterogeneity, we performed single-cell RNA sequencing on human colon organoids (HCOs) derived from three healthy adult donors following EAEC 042 infection. Surprisingly, despite comparable EAEC adherence across donors, we observed striking donor-specific responses to infection at multiple levels. A total of seven distinct colonic epithelial cell clusters were identified, with striking donor-specific baseline compositions. Following infection, the HCO donors exhibited three distinct response phenotypes evident in both cell type remodeling and gene regulation: hyperresponsive, intermediate, and non-responsive. We further observed extensive donor-specific cell-cell communication networks at baseline and after EAEC infection. This study suggests that the heterogeneity in host epithelial response to EAEC infection extends to the single-cell level. While the colonic regions from which the HCOs were derived represent a potential confounding factor, the magnitude of organoid-to-organoid variation exceeded previously reported regional differences, suggesting intrinsic host factors as a crucial part of response heterogeneity. These findings establish a paradigm for understanding infectious disease susceptibility through the human organoid model system.IMPORTANCEUnderstanding why similar pathogen exposures produce vastly different clinical outcomes is critical for combating infectious diseases. By conducting single-cell RNA sequencing on human colon organoids derived from three different donors, we show that each donor possesses unique intrinsic cellular compositions and distinct transcriptomic responses to enteroaggregative <i>Escherichia coli</i> (EAEC) infection. These findings challenge the traditional pathogen-focused paradigm and highlight the critical role of host factors in infectious disease outcomes. This study also validates human organoids as a powerful platform for studying host heterogeneity, which may help predict disease susceptibility and optimize treatment for diverse patient populations in the future.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0075825"},"PeriodicalIF":4.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148707473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel integrative and conjugative element in <i>Streptococcus pyogenes</i> carries a <i>cfr</i>-like gene associated with linezolid resistance in other species.","authors":"Daniel B Amusin, Lacy M Simons, Dulce S Garcia, Alan R Hauser, Emma Office, Preeti Jaggi, David B Williams, Larry K Kociolek, Ami B Patel, Stanford T Shulman, Judith A Guzman-Cottrill, Robert R Tanz, Egon A Ozer","doi":"10.1128/msphere.00277-26","DOIUrl":"10.1128/msphere.00277-26","url":null,"abstract":"<p><p>Treatment of severe invasive <i>Streptococcus pyogenes</i> infections has historically relied on β-lactam antibiotics with adjunctive clindamycin. Rising rates of lincosamide resistance have led to adoption of linezolid as an alternative adjunctive therapy. This report describes a clinical <i>S. pyogenes</i> isolate carrying a multi-drug resistance gene, <i>cfr</i>(C), known to confer the phenicol, lincosamide, oxazolidinone, pleuromutilin, and streptogramin A (PhLOPS_A) resistance phenotype in other bacterial species. Strain GAS-390756 is a pharyngeal isolate collected from a child with pharyngitis in the United States. Whole-genome sequence analysis demonstrated that the isolate belonged to <i>emm</i> type 89 and carried an integrative and conjugative element with <i>erm</i>(B) and <i>cfr</i>(C) cargo genes (ICE<i>Spy</i>390756). Antimicrobial susceptibility testing demonstrated the isolate was resistant to erythromycin and clindamycin but susceptible to linezolid, consistent with the activity of <i>erm</i>(B) but not <i>cfr</i>(C). Comparative analysis of <i>cfr</i>(C)'s genomic context suggested that the promoter sequence may have been lost during ICE<i>Spy</i>390756's acquisition of the gene. While GAS-390756 remains susceptible to linezolid, the expansion of <i>cfr</i>(C)'s host range into <i>S. pyogenes</i> and its presence on a novel mobile element are concerning. In light of known expression mechanisms for other silent antimicrobial resistance genes, this observation carries epidemiologic and public health importance.</p><p><strong>Importance: </strong>Treatment of severe invasive <i>Streptococcus pyogenes</i> infection has traditionally relied on the adjunctive use of clindamycin with β-lactam antibiotic therapy. However, rising rates of clindamycin non-susceptibility have led clinicians to adopt linezolid as an alternative therapy. We identified <i>S. pyogenes</i> isolated from a child with pharyngitis that carried the <i>cfr</i>(C) gene. This gene causes resistance to multiple antibiotics, including clindamycin and linezolid, in other bacterial species. At the time of this study, we found no other instances of the <i>cfr</i>(C) gene carried by <i>S. pyogenes</i> in either published reports or the public genome sequence database. While this isolate remained sensitive to linezolid, the expanded host range of <i>cfr</i>(C) found in a novel potentially mobile genomic element may herald the eventual emergence of broader antibiotic resistance in <i>S. pyogenes</i>.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0027726"},"PeriodicalIF":4.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}