mSphere最新文献

{"title":"Discovery of novel anti-<i>Prototheca</i> compounds with diverse modes of action through screening of a chemical library.","authors":"Amir Aliramezani, Magdalena Widziolek, Łukasz Chajec, Gabriela A Żyłka, Beatrycze Nowicka, Izabela Ciastoń, Patrizia Danesi, Tomasz Jagielski, Magdalena Rost-Roszkowska, Tomasz K Prajsnar, Jakub M Kwiecinski","doi":"10.1128/msphere.00427-26","DOIUrl":"https://doi.org/10.1128/msphere.00427-26","url":null,"abstract":"<p><p><i>Prototheca</i>, a genus of unpigmented yeast-like microscopic algae, is an emerging pathogen of humans and animals. Treatment of <i>Prototheca</i> infections is often unsuccessful because the unusual algal biology of these pathogens limits the availability of effective therapeutics. Here, we screened the Pandemic Response Box, a library of 400 compounds with potential anti-infective activity that are either clinically approved or in preclinical development, and identified five promising compounds with anti-<i>Prototheca</i> activity: tafenoquine, OSU-03012, alexidine, ciclopirox, and eberconazole. Characterized alongside amphotericin B, which is currently often used for treatment, these identified compounds displayed potent activity against multiple <i>Prototheca</i> strains and species by inhibiting growth, killing the algae, and disrupting biofilms. Their diverse mechanisms of action included effects on cell walls and membranes, mitochondrial dysfunction, ROS overproduction, metabolic alterations, and induction of apoptosis. Most of the identified compounds were also effective against <i>in vivo Prototheca</i> infection in larval zebrafish, highlighting their translational potential and the possibility of future introduction into clinical practice.IMPORTANCEThis study addresses the emerging threat of infections caused by <i>Prototheca</i>, a group of unusual algae that can cause difficult-to-treat infections in both humans and animals. Current treatment options are limited and often ineffective, highlighting the need to develop new therapeutic strategies, especially as reported cases of <i>Prototheca</i> infections quickly increase. Here, we identified several compounds with strong activity against <i>Prototheca</i>. These agents not only blocked growth but also killed the microorganisms, damaged their biofilms, and reduced infection in an animal model. Importantly, many of the identified compounds are already used clinically for other indications, which raises the possibility of rapid repurposing against <i>Prototheca</i>. Moreover, we identified multiple mechanisms responsible for these compounds' activity, providing a framework for the future development of even more potent anti-<i>Prototheca</i> therapies.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0042726"},"PeriodicalIF":4.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tropolone and hinokitiol act against <i>Staphylococcus aureus</i> by concentration-dependent iron restriction or toxic iron overload.","authors":"Bethany L Hardman, Gary J Sharples","doi":"10.1128/msphere.00619-26","DOIUrl":"https://doi.org/10.1128/msphere.00619-26","url":null,"abstract":"<p><p>Transition metal homeostasis is a critical component of bacterial physiology and thus represents a promising opportunity for antimicrobial intervention. Here, we demonstrate that the naturally occurring chelators tropolone (TRO) and hinokitiol (HNK) inhibit <i>Staphylococcus aureus</i> growth through concentration-dependent shifts in metal stress. Integrated metallomic and transcriptomic profiling revealed that low doses of both compounds promote toxic iron loading and a PerR-regulated oxidative stress response, consistent with iron-induced redox toxicity. However, at higher concentrations, both chelators trigger iron and manganese starvation responses, copper and zinc accumulation, and repression of respiratory and fermentative pathways, consistent with widespread disruption of metal homeostasis and failed metabolic adaptation. Despite these broadly similar responses, TRO, but not HNK, produced an unexpected biphasic growth phenotype. Experiments confirmed an analogous response in the distantly related gram-positive species <i>Bacillus subtilis</i>. These findings highlight how small molecule chelators can interfere with multiple metal systems to disrupt bacterial metabolism and how TRO can be exploited in a dose-dependent fashion to disrupt <i>S. aureus</i> proliferation.</p><p><strong>Importance: </strong>There is an urgent need to develop alternative therapies to combat the drug-resistant pathogen <i>Staphylococcus aureus</i>. One solution is to disrupt the intricate balance of metal availability using small-molecule chelators. We show that tropolone and hinokitiol arrest bacterial growth at low and high doses by radically different mechanisms. At low concentrations, both chelators induce iron overload, whereas at higher concentrations, access to iron and manganese is blocked, and instead, toxic levels of intracellular copper accumulate. Despite the similarity in their cellular effects, only tropolone confers bacterial growth restriction at low and high doses, while permitting recovery at intermediate levels. Such contrasting concentration-dependent antibacterial activities could be harnessed, by iterative switching of doses, to radically perturb metal metabolism as a unique means to control <i>S. aureus</i> infections.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0061926"},"PeriodicalIF":4.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of oral and gut microbiome highlights the role of oral bacteria in systemic inflammation in HIV.","authors":"Jennifer A Fulcher, Katharine P Newman, Bryan T Pham, Fan Li, Grace D Cho, Julie Elliott, Nicole H Tobin, Steven Shoptaw, Pamina M Gorbach, Grace M Aldrovandi","doi":"10.1128/msphere.00384-26","DOIUrl":"10.1128/msphere.00384-26","url":null,"abstract":"<p><p>Chronic HIV-1 infection is associated with increased inflammation-related comorbidities, despite effective viral suppression with antiretroviral therapy. While the role of the gut microbiome in inflammation is well studied, the contribution of the oral microbiome remains less clear. This study investigates the relationship between the oral and gut microbiomes in driving systemic inflammation in persons with HIV. This cross-sectional study utilized archived samples from 198 participants (99 with HIV and 99 without HIV). Oral and gut microbiome composition was analyzed via 16S rRNA sequencing, and systemic inflammatory biomarkers were measured using multiplex assays. Bacterial inflammatory potential was assessed through <i>in vitro</i> co-culture and epithelial barrier permeability assays. The oral microbiome in HIV was characterized by increased <i>Veillonella</i>, <i>Capnocytophaga</i>, and <i>Megasphaera</i>, and several decreased genera including <i>Fusobacterium</i>. Using permutational multivariate analysis of variance, we found that the oral microbiome was a significant driver of cytokine variation in HIV compared to the gut microbiome and identified specific associations with oral <i>Veillonella</i> and <i>Megasphaera</i>. We found no differences in anti-<i>Veillonella parvula</i> serum IgG by HIV status, but IgG titers did correlate with microbial translocation markers sCD14 and LBP in HIV. <i>In vitro</i> studies demonstrated that <i>Veillonella parvula</i> increased oral epithelial barrier permeability and induced monocyte activation. These studies suggest that the oral microbiome, particularly <i>Veillonella parvula</i>, may contribute to systemic inflammation in HIV through mechanisms involving epithelial barrier disruption, oral translocation, and monocyte activation.</p><p><strong>Importance: </strong>In HIV, persistent inflammation contributes to the elevated risk of cardiovascular disease, metabolic disorders, and other non-AIDS comorbidities. Alterations in the gut microbiome and resultant microbial translocation are contributors to this ongoing inflammation. Most microbiome research has focused on the gut compartment, though there is increasing appreciation for the role of the oral microbiome in chronic inflammatory diseases. Few studies have systematically compared the oral and gut compartments in HIV-associated inflammation. In this study, we identify <i>Veillonella parvula</i> as a plausible oral driver of epithelial barrier disruption and immune activation, expanding current understanding of microbial contributors to persistent inflammation in HIV.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0038426"},"PeriodicalIF":4.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Candidozyma auris</i> (<i>Candida auris</i>) as a harbinger of novel fungal pathogens.","authors":"Carla E Schuh, Chaitanya S Gokhale","doi":"10.1128/msphere.00109-26","DOIUrl":"https://doi.org/10.1128/msphere.00109-26","url":null,"abstract":"<p><p>Mammals are protected from fungal pathogens by two evolutionary pillars: adaptive immunity and elevated body temperature. Anthropogenic climate change is eroding this thermal barrier, while a concurrent decline in human basal body temperature accelerates convergence from both directions. <i>Candida auris</i>, a thermotolerant, multidrug-resistant pathogen, arose independently as genetically distinct clades on multiple continents, a pattern implicating shared selective pressures rather than clonal spread. Unlike its closest relatives, which grow poorly at mammalian temperatures, it thrives at 37°C, tolerates up to 47°C, persists on hospital surfaces, resists all three major antifungal classes, and causes invasive infections with 30-60% mortality. We review its evolutionary biology, ecology, and clinical significance, evaluating hypotheses for its origin, and the mechanisms underlying its thermotolerance and virulence. <i>C. auris</i> may be the first of many fungi adapting to breach mammalian thermal defenses, making predictive frameworks for fungal disease emergence an urgent priority.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0010926"},"PeriodicalIF":4.0,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A widespread actinobacterial G protein system regulates production of specialized metabolites in <i>Streptomyces coelicolor</i>.","authors":"Luis M Cantu Morin, Aditya Vunnum, Sydney Binns, Matthew F Traxler","doi":"10.1128/msphere.00568-25","DOIUrl":"10.1128/msphere.00568-25","url":null,"abstract":"<p><p>Actinobacterial G protein systems (AGPSs), encoded by operons called conservons, are regulatory systems that are broadly distributed within Actinomycetota. AGPSs contain a minimum of four proteins, namely, a sensor histidine kinase, a small Ras-like GTPase, a roadblock/MglB protein (likely a GTPase activating protein), and a protein that likely functions as a guanine-nucleotide exchange factor (GEF). While progress has been made in understanding AGPS function at the mechanistic level, the phylogenetic distribution of individual AGPSs and the genes and processes they regulate remain largely unmapped. Previously, the Cvn8 AGPS of <i>Streptomyces coelicolor</i> was found to influence expression of genes in multiple specialized metabolic pathways during interspecies interactions with other actinomycetes. However, the impact of the Cvn8 AGPS on specialized metabolism has not been assessed at the chemical level. Here, we investigated the phylogenetic distribution of the Cvn8 AGPS clade and assessed the impact of the Cvn8 AGPS on natural product biosynthesis using untargeted metabolomics. In a set of 485 actinobacterial genomes, we found that members of the clade that includes the Cvn8 AGPS from <i>S. coelicolor</i> are widely distributed in Actinomycetota known to produce specialized metabolites. We also found that in <i>S. coelicolor</i>, the pattern of specialized metabolite production varied in mutants lacking individual components of the Cvn8 AGPS. Specifically, normal production of the pigmented antibiotics actinorhodin and undecylprodiginine during interspecies interactions required <i>cvnA8</i> and <i>cvnF8</i>, while a Δ<i>cvnD8</i> strain overproduced undecylprodiginine. Together, these results connect a widespread AGPS to control of specialized metabolism in a model actinomycete.IMPORTANCEActinobacterial G protein systems (AGPSs) are found widely in bacteria in the phylum Actinomycetota, including genera like <i>Streptomyces</i> that produce many useful molecules, and pathogens such as <i>Mycobacterium tuberculosis</i>. The genes and functions regulated by these regulatory systems are largely unknown. Here, we investigated the role of the Cvn8 AGPS in controlling the production of specialized metabolites like antibiotics in the model actinomycete, <i>Streptomyces coelicolor</i>. We found that specific components of the Cvn8 AGPS were required for the normal production of the antibiotics actinorhodin and undecylprodiginine during interactions between <i>S. coelicolor</i> and another actinomycete. We also show that Cvn8 belongs to a group of AGPSs that is found broadly in the genus <i>Streptomyces</i> and in more distantly related orders of Actinomycetota, such as the Pseudonorcardiales and Micromonosporales. Together, these results raise the possibility that this group of AGPSs may influence specialized metabolism across a broad range of Actinomycetota lineages.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0056825"},"PeriodicalIF":4.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148761276","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":"Strain-specific outer membrane vesicle-mediated transfer of a <i>bla</i>_OXA-24-like plasmid in <i>Acinetobacter baumannii</i> restricts cross-species dissemination.","authors":"Shengnan Jiang, Biyong Yan, Haiyang Liu, Long Sun, Yan Chen, Lilin Liu, Yunsong Yu","doi":"10.1128/msphere.00311-26","DOIUrl":"10.1128/msphere.00311-26","url":null,"abstract":"&lt;p&gt;&lt;p&gt;The rapid rise of multidrug-resistant &lt;i&gt;Acinetobacter&lt;/i&gt; spp. poses a major global health threat. In &lt;i&gt;Acinetobacter&lt;/i&gt; spp., carbapenem resistance is frequently mediated by OXA-type carbapenemases encoded by &lt;i&gt;bla&lt;/i&gt;&lt;sub&gt;OXA&lt;/sub&gt; genes, including &lt;i&gt;bla&lt;/i&gt;&lt;sub&gt;OXA-24&lt;/sub&gt;-like genes such as &lt;i&gt;bla&lt;/i&gt;&lt;sub&gt;OXA-72&lt;/sub&gt;. Outer membrane vesicles (OMVs) are nanoscale proteoliposomes secreted by Gram-negative bacteria that can facilitate plasmid transfer, yet the mechanisms limiting their dissemination remain unclear. Nationwide screening in China of 2,880 &lt;i&gt;Acinetobacter&lt;/i&gt; clinical isolates identified 10 strains carrying &lt;i&gt;bla&lt;/i&gt;&lt;sub&gt;OXA-24&lt;/sub&gt; and &lt;i&gt;bla&lt;/i&gt;&lt;sub&gt;OXA-72&lt;/sub&gt; plasmids across three species (&lt;i&gt;A. baumannii&lt;/i&gt;, &lt;i&gt;A. pittii&lt;/i&gt;, and &lt;i&gt;A. baylyi&lt;/i&gt;). Sequencing revealed nine distinct plasmids, most bearing a Rep_3/OrfX C-module backbone with &lt;i&gt;blaOXA&lt;/i&gt;-p&lt;i&gt;dif&lt;/i&gt; resistance modules (9/10). Among clinical strains, A2485 was identified as a high-OMV producer (2.74 ± 0.20-fold relative to ATCC 17978, &lt;i&gt;P&lt;/i&gt; &lt; 0.001). OMVs from A2485 transferred the &lt;i&gt;bla&lt;/i&gt;&lt;sub&gt;OXA-72&lt;/sub&gt; plasmid to ATCC 17978 at 1.9 × 10⁻⁷ transformants per CFU, exceeding direct supernatant transfer at 3.2 × 10⁻⁸ transformants per CFU, and conferred resistance to meropenem, ceftazidime, and cefoperazone/sulbactam. Transfer was strictly donor-specific, with no transmission observed across 13 non-&lt;i&gt;A&lt;/i&gt;. &lt;i&gt;baumannii&lt;/i&gt; strains, and recipient strains failed to retransmit the plasmid, indicating a strong cross-species barrier and a non-reciprocal, donor-dependent process. Although all strains produced intact OMVs and encapsulated plasmid DNA, packaging efficiency varied considerably by host (~4.5-28.6 ng/μg). Strains with DNA loading (17978E/17978V: 28.62 and 23.98 ng/μg) equal to or exceeding that of donor A2485 (13.62 ng/μg) remained incapable of transfer. These findings demonstrate that dissemination is constrained by host-specific, post-packaging barriers rather than packaging efficiency, limiting resistance spread to specific lineages while enabling localized adaptation.IMPORTANCE&lt;i&gt;Acinetobacter baumannii&lt;/i&gt; is a leading hospital-associated pathogen, and carbapenem resistance mediated by &lt;i&gt;bla&lt;/i&gt;&lt;sub&gt;OXA-24&lt;/sub&gt;-like genes poses a serious clinical challenge. Through nationwide screening of 2,880 clinical &lt;i&gt;Acinetobacter&lt;/i&gt; isolates in China, we found that strains carrying &lt;i&gt;bla&lt;/i&gt;&lt;sub&gt;OXA-24&lt;/sub&gt; and &lt;i&gt;bla&lt;/i&gt;&lt;sub&gt;OXA-72&lt;/sub&gt; plasmids are relatively rare, occurring in only 10 isolates across three species. We provide the first evidence that outer membrane vesicle (OMV)-mediated plasmid transfer is subject to strict, host-specific barriers: the &lt;i&gt;bla&lt;/i&gt;&lt;sub&gt;OXA-72&lt;/sub&gt; plasmid was successfully transferred among &lt;i&gt;A. baumannii&lt;/i&gt; strains via OMVs, yet no transfer was observed to any of the 13 non-&lt;i&gt;A&lt;/i&gt;. &lt;i&gt;baumannii&lt;/i&gt; species tested. Transfer was also non-reciprocal-recipient strains that acquired the plasmid we","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0031126"},"PeriodicalIF":4.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795905","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":"Airflow constraints govern natural airborne transmission of tuberculosis.","authors":"Kubra F Naqvi, Yuhui Guo, Yash Kulkarni, Deepak Sapkota, Pei Lu, Shibo Wang, Beatriz R S Dias, Victoria A Ektnitphong, Arabella E Martin, Bret M Evers, Lenette L Lu, Hui Ouyang, Lydia Bourouiba, Michael U Shiloh","doi":"10.1128/msphere.00228-26","DOIUrl":"10.1128/msphere.00228-26","url":null,"abstract":"<p><p>Tuberculosis (TB) spreads through the air, yet the physical conditions that permit effective airborne transmission remain poorly defined. Although early 20th-century guinea pig studies demonstrated efficient transmission of <i>Mycobacterium tuberculosis</i> (Mtb), this experimental paradigm has not been reestablished in modern high-containment facilities. Here, we show that airflow can impose constraints that suppress or permit biologically effective exposure between infected and susceptible hosts. Using a guinea pig model of animal-to-animal exposure, we combined transmission experiments with quantitative particle tracking and particle transport modeling to explain why some housing configurations fail to support effective exposure. Static environments and excessive unidirectional airflow prevented transmission, whereas controlled low-velocity airflow restored evidence of exposure, including tuberculin skin test conversion, antigen-specific immune responses, and pulmonary inflammation consistent with early infection. These findings identify airflow as a critical constraint on airborne TB transmission and establish a reproducible experimental framework for dissecting host, microbial, and environmental determinants of spread.</p><p><strong>Importance: </strong>Tuberculosis remains one of the leading causes of death from infectious disease worldwide, and its spread depends on airborne transmission of <i>Mycobacterium tuberculosis</i>. Yet surprisingly little is known about the physical conditions that determine when transmission actually occurs. Classic experiments in guinea pigs demonstrated airborne spread of tuberculosis, but these systems have been difficult to reproduce in modern high-containment laboratories. In this study, we show that airflow conditions can determine whether pathogen-containing aerosols persist long enough to expose a susceptible host. By identifying airflow as a key constraint on transmission and establishing an experimental system that functions under contemporary biosafety conditions, this work provides a platform to experimentally dissect how microbial, host, and environmental factors interact to shape tuberculosis spread.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0022826"},"PeriodicalIF":4.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795899","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":"Temporal succession of microbiomes and resistomes during buried rat carcass decomposition.","authors":"Daijing Yu, Liuyaoxing Zhang, Damu Agu, Niu Gao, Yuntian Xiao, Meng Zhang, Jun Zhang, Jiangwei Yan","doi":"10.1128/msphere.00437-26","DOIUrl":"10.1128/msphere.00437-26","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Burial is a prevalent approach for disposing of human and animal carcass. Carcass decomposition is a key natural disturbance that reshapes microbial communities and modulates biogeochemical cycles. Animal intestines serve as critical natural reservoirs of antibiotic resistance genes (ARGs), and carcass decomposition concurrently remodels intestinal bacterial assemblages and resistome profiles. Most previous studies have characterized microbial succession in surface-exposed carcasses, yet the coordinated temporal shifts of intestinal microbiota, resistomes, and horizontal gene transfer (HGT) signatures within buried carcasses remain underexplored. We established a buried rat carcass model and performed metagenomic sequencing to characterize temporal dynamics of intestinal bacteria, ARGs, mobile genetic elements (MGEs), and HGT events. Bacterial communities underwent directional succession accompanied by reduced α-diversity and stage-specific β-diversity. Proteobacteria gradually outcompeted Firmicutes and Bacteroidetes to become dominant taxa. The resistome followed regular temporal changes: tetracycline and macrolide-lincosamide-streptogramin (MLS) ARGs prevailed in early decomposition, while multidrug, β-lactam, polymyxin, and quinolone ARGs accumulated in mid-late stages, with ARG richness peaking on day 28. Approximately 83% of temporally dynamic ARG subtypes were positively correlated with decomposition duration. Procrustes analysis (&lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.859) revealed strong correlations between bacterial succession and resistome dynamics, with Proteobacteria as potential multidrug-resistant hosts and major HGT donors. This study identifies a correlative cascade of microbial succession that drives MGE functional shift, which in turn increased HGT potential and ultimately leads to resistome accumulation in buried carcass intestinal habitats. These findings expand the theoretical framework of disturbance-driven microbial-resistome co-succession and offer insights into drivers of antibiotic resistance propagation in terrestrial cadaver systems.IMPORTANCEAnimal carcass burial is a ubiquitous natural terrestrial disturbance, and carcass intestinal contents represent a major endogenous reservoir of environmental antibiotic resistance genes (ARGs). Although extensive research has characterized microbial succession of exposed carcasses, the co-occurrence patterns of gut microbiome and resistome together with associated horizontal gene transfer (HGT) under buried conditions remain underexplored. Using metagenomic profiling of decomposing rat intestinal feces, this study explores a potential correlative cascade spanning bacterial succession, mobile genetic element (MGE) functional shifts, increased HGT potential, and gradual ARG enrichment. Our findings expand the ecological data set focused on subsurface buried carcass habitats and advance mechanistic knowledge of coupled microbiome-resistome succession driven by postmortem decomposition.&lt;/p","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0043726"},"PeriodicalIF":4.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148712419","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":"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}