mSphere最新文献

{"title":"SARS-CoV-2 outbreak in lions, tigers, and hyenas at Denver Zoo.","authors":"Emily N Gallichotte, Laura Bashor, Katelyn Erbeck, Lara Croft, Katelyn Stache, Jessica Long, Sue VandeWoude, James C Johnson, Kristy L Pabilonia, Gregory D Ebel","doi":"10.1128/msphere.00989-24","DOIUrl":"10.1128/msphere.00989-24","url":null,"abstract":"<p><p>In late 2019, SARS-CoV-2 spilled over from an animal host into humans, where it efficiently spread, resulting in the COVID-19 pandemic. Through both natural and experimental infections, we learned that many animal species are susceptible to SARS-CoV-2. Importantly, animals in close proximity to humans, including companion, farmed, and those at zoos and aquariums, became infected, and many studies demonstrated transmission to/from humans in these settings. In this study, we first review the literature of SARS-CoV-2 infections in tigers and lions and compare species, sex, age, virus and antibody detection assay, and types, frequency, and length of clinical signs, demonstrating broad heterogeneity among infections. We then describe a SARS-CoV-2 outbreak in lions, tigers, and hyenas at Denver Zoo in late 2021. Animals were tested for viral RNA (vRNA) for 4 months. Lions had significantly more vRNA in nasal swabs than both tigers and hyenas, and many individual lions experienced viral recrudescence after weeks of undetectable vRNA. Infectious virus was correlated with high levels of vRNA and was more likely to be detected earlier during infection. Four months post-infection, all tested animals generated robust neutralizing antibody titers. Animals were infected with Delta lineage AY.20 identical to a variant circulating at less than 1% in Colorado humans at that time, suggesting a single spillover event from an infected human spread within and between species housed at the zoo. Better understanding of epidemiology and susceptibility of SARS-CoV-2 infections in animals is critical to limit the current and future spread and protect animal and human health.IMPORTANCESurveillance and experimental testing have shown many animal species, including companion, wildlife, and conservatory, are susceptible to SARS-CoV-2. Early in the COVID-19 pandemic, big cats at zoological institutions were among the first documented cases of naturally infected animals; however, challenges in the ability to collect longitudinal samples in zoo animals have limited our understanding of SARS-CoV-2 kinetics and clearance in these settings. We measured SARS-CoV-2 infections over 4 months in lions, tigers, and hyenas at Denver Zoo and detected viral RNA, infectious virus, neutralizing antibodies, and recrudescence after initial clearance. We found lions had longer and higher levels of virus compared to the other species. All animals were infected by a rare viral lineage circulating in the human population, suggesting a single spillover followed by interspecies transmission. These data are important in better understanding natural SARS-CoV-2 spillover, spread, and infection kinetics within multiple species of zoo animals.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0098924"},"PeriodicalIF":3.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256007","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":"Predictive signatures of immune response to vaccination and implications of the immune setpoint remodeling.","authors":"Irene Ramos","doi":"10.1128/msphere.00502-24","DOIUrl":"10.1128/msphere.00502-24","url":null,"abstract":"<p><p>In 2020, I featured two articles in the \"mSphere of Influence\" commentary series that had profound implications for the field of immunology and helped shape my research perspective. These articles were \"Global Analyses of Human Immune Variation Reveal Baseline Predictors of Postvaccination Responses\" by Tsang et al. (Cell 157:499-513, 2014, https://doi.org/10.1016/j.cell.2014.03.031) and \"A crowdsourced analysis to identify ab initio molecular signatures predictive of susceptibility to viral infection\" by Fourati et al. (Nat Commun 9:4418, 2018, https://doi.org/10.1038/s41467-018-06735-8). From these topics, the identification of signatures predictive of immune responses to vaccination has greatly advanced and pivoted our understanding of how the immune state at the time of vaccination predicts (and potentially determines) vaccination outcomes. While most of this work has been done using influenza vaccination as a model, pan-vaccine signatures have been also identified. The key implications are their potential use to predict who will respond to vaccinations and to inform strategies for fine-tuning the immune setpoint to enhance immune responses. In addition, investigations in this area led us to understand that immune perturbations, such as acute infections and vaccinations, can remodel the baseline immune state and alter immune responses to future exposures, expanding this exciting field of research. These processes are likely epigenetically encoded, and some examples have already been identified and are discussed in this minireview. Therefore, further research is essential to gain a deeper understanding of how immune exposures modify the epigenome and transcriptome, influence the immune setpoint in response to vaccination, and define its exposure-specific characteristics.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0050224"},"PeriodicalIF":3.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033756","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":"Fermentative profile and bacterial community structure of whole-plant triticale silage (<i>Triticosecale Wittmack</i>) with or without the addition of <i>Streptococcus bovis</i> and <i>Lactiplantibacillus plantarum</i>.","authors":"Yujie Niu, Yaya Guo, Rongzheng Huang, Junli Niu, Yan Wang, Peng Zhang, Qicheng Lu, Wenju Zhang","doi":"10.1128/msphere.00894-24","DOIUrl":"10.1128/msphere.00894-24","url":null,"abstract":"&lt;p&gt;&lt;p&gt;This study aimed to investigate the effects of &lt;i&gt;Streptococcus bovis&lt;/i&gt; and &lt;i&gt;Lactiplantibacillus plantarum&lt;/i&gt; on the chemical composition, fermentation characteristics, bacterial communities, and predicted metabolic pathways of whole-plant triticale silage (&lt;i&gt;Triticosecale Wittmack&lt;/i&gt;). Fresh triticale harvested at the milk stage was ensiled in sterile distilled water (CON), &lt;i&gt;Streptococcus bovis&lt;/i&gt; (ST), &lt;i&gt;Lactiplantibacillus plantarum&lt;/i&gt; (LP), and a combination of &lt;i&gt;S. bovis&lt;/i&gt; and &lt;i&gt;L. plantarum&lt;/i&gt; (LS) for 3, 7, 15, and 30 days. During ensiling, the pH and water-soluble carbohydrate (WSC) content in the inoculated groups was significantly lower than those in the CON group (&lt;i&gt;P&lt;/i&gt; &lt; 0.05), especially in the LS group (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). After 7 days of ensiling, the ST and LS groups had lower (&lt;i&gt;P&lt;/i&gt; &lt; 0.05) starch content and higher (&lt;i&gt;P&lt;/i&gt; &lt; 0.05) concentrations of lactic acid (LA) and acetic acid (AA). Inoculation with &lt;i&gt;S. bovis&lt;/i&gt; and &lt;i&gt;L. plantarum&lt;/i&gt;, either alone or in combination, increased the abundance of &lt;i&gt;Lactobacillus&lt;/i&gt; and &lt;i&gt;Pediococcus&lt;/i&gt; while reducing the abundance of &lt;i&gt;Weissella&lt;/i&gt;, &lt;i&gt;Rosenbergiella&lt;/i&gt;, &lt;i&gt;Pantoea&lt;/i&gt;, and &lt;i&gt;Enterobacter&lt;/i&gt;. Metabolic prediction analysis indicated that inoculation with &lt;i&gt;S. bovis&lt;/i&gt; enhanced starch and sucrose metabolism during the early stages of ensiling. The abundance of &lt;i&gt;Streptococcus&lt;/i&gt; positively correlated with LA (&lt;i&gt;P&lt;/i&gt; &lt; 0.05) and AA concentration but negatively correlated with starch content, pH, and propionic acid (PA) concentration (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). &lt;i&gt;S. bovis&lt;/i&gt; inoculation increased starch hydrolysis and carbohydrate metabolism during the early stages. &lt;i&gt;S. bovis&lt;/i&gt; and &lt;i&gt;L. plantarum&lt;/i&gt; synergistically improved the fermentation characteristics and bacterial communities of triticale silage. Therefore, &lt;i&gt;S. bovis&lt;/i&gt; can be used as an additive or for a fast start-up agent to improve silage fermentation quality.IMPORTANCEEnsiling is a widely used method for preserving fresh forage. Silage quality is determined by the chemical and microbial composition. Studies have shown that &lt;i&gt;S. bovis&lt;/i&gt; grew faster than commercial species, thereby creating advantages for other lactic acid bacteria during ensiling. Therefore, we believe that &lt;i&gt;S. bovis&lt;/i&gt; and &lt;i&gt;L. plantarum&lt;/i&gt; can synergistically improve the fermentation characteristics and bacterial community in silage. However, few studies use high-throughput methods to explain the impact of &lt;i&gt;S. bovis&lt;/i&gt; on silage fermentation. Results showed that &lt;i&gt;S. bovis&lt;/i&gt; significantly affected the fermentation parameters, bacterial community, and metabolic characteristics of triticale silage. &lt;i&gt;S. bovis&lt;/i&gt; and &lt;i&gt;L. plantarum&lt;/i&gt; synergistically accelerated the fermentation, reducing pH and WSC while increasing lactic acid and acetic acid concentrations in the early stages of ensiling. Additionally, co-inoculation increased the abundance of &lt;i&gt;Lactobacillus&lt;/i&gt; and &lt;i&gt;Pediococcus&lt;/i&gt; ","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0089424"},"PeriodicalIF":3.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053019","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":"Dysregulation of lung epithelial cell homeostasis and immunity contributes to Middle East respiratory syndrome coronavirus disease severity.","authors":"Amy C Sims, Alexandra Schäfer, Kenichi Okuda, Sarah R Leist, Jacob F Kocher, Adam S Cockrell, Padraig E Hawkins, Minako Furusho, Kara L Jensen, Jennifer E Kyle, Kristin E Burnum-Johnson, Kelly G Stratton, Natalie C Lamar, Carrie D Niccora, Karl K Weitz, Richard D Smith, Thomas O Metz, Katrina M Waters, Richard C Boucher, Stephanie A Montgomery, Ralph S Baric, Timothy P Sheahan","doi":"10.1128/msphere.00951-24","DOIUrl":"10.1128/msphere.00951-24","url":null,"abstract":"<p><p>Coronaviruses (CoV) emerge suddenly from animal reservoirs to cause novel diseases in new hosts. Discovered in 2012, the Middle East respiratory syndrome coronavirus (MERS-CoV) is endemic in camels in the Middle East and is continually causing local outbreaks and epidemics. While all three newly emerging human CoVs from the past 20 years (SARS-CoV, SARS-CoV-2, and MERS-CoV) cause respiratory disease, each CoV has unique host interactions that drive differential pathogeneses. To better understand the virus and host interactions driving lethal MERS-CoV infection, we performed a longitudinal multi-omics analysis of sublethal and lethal MERS-CoV infection in mice. Significant differences were observed in body weight loss, virus titers, and acute lung injury among lethal and sub-lethal virus doses. Virus-induced apoptosis of type I and II alveolar epithelial cells suggests that loss or dysregulation of these key cell populations was a major driver of severe disease. Omics analysis suggested differential pathogenesis was multi-factorial with clear differences among innate and adaptive immune pathways as well as those that regulate lung epithelial homeostasis. Infection of mice lacking functional T and B cells showed that adaptive immunity was important in controlling viral replication but also increased pathogenesis. In summary, we provide a high-resolution host response atlas for MERS-CoV infection and disease severity. Multi-omics studies of viral pathogenesis offer a unique opportunity to not only better understand the molecular mechanisms of disease but also to identify genes and pathways that can be exploited for therapeutic intervention all of which is important for our future pandemic preparedness.IMPORTANCEEmerging coronaviruses like SARS-CoV, SARS-CoV-2, and MERS-CoV cause a range of disease outcomes in humans from an asymptomatic, moderate, and severe respiratory disease that can progress to death but the factors causing these disparate outcomes remain unclear. Understanding host responses to mild and life-threatening infections provides insight into virus-host networks within and across organ systems that contribute to disease outcomes. We used multi-omics approaches to comprehensively define the host response to moderate and severe MERS-CoV infection. Severe respiratory disease was associated with dysregulation of the immune response. Key lung epithelial cell populations that are essential for lung function get infected and die. Mice lacking key immune cell populations experienced greater virus replication but decreased disease severity implicating the immune system in both protective and pathogenic roles in response to MERS-CoV. These data could be utilized to design new therapeutic strategies targeting specific pathways that contribute to severe disease.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0095124"},"PeriodicalIF":3.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066872","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":"Emerging themes in microbial stress response and mechanistic insights: key findings from the fall 2024 ASM Theobald Smith Society meeting.","authors":"Duhita Sant, Akilah I Mateen, Raymond F Sullivan, Jeffrey M Boyd, Valerie J Carabetta, Srujana S Yadavalli, Jennifer S Sun","doi":"10.1128/msphere.01008-24","DOIUrl":"10.1128/msphere.01008-24","url":null,"abstract":"<p><p>The annual fall meeting for the Theobald Smith Society was held in November 2024 on the campus of Rutgers University-New Brunswick. Eighty-six branch members from across New Jersey attended the meeting, composed of undergraduate, graduate, and postdoctoral trainees, faculty members, and government and industry professionals. This report highlights the breadth and diversity of research conducted by American Society for Microbiology members in the Theobald Smith Society and celebrates their groundbreaking discoveries.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0100824"},"PeriodicalIF":3.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979307","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":"PRRSV-2 variant classification: a dynamic nomenclature for enhanced monitoring and surveillance.","authors":"Kimberly VanderWaal, Nakarin Pamornchainavakul, Mariana Kikuti, Jianqiang Zhang, Michael Zeller, Giovani Trevisan, Stephanie Rossow, Mark Schwartz, Daniel C L Linhares, Derald J Holtkamp, João Paulo Herrera da Silva, Cesar A Corzo, Julia P Baker, Tavis K Anderson, Dennis N Makau, Igor A D Paploski","doi":"10.1128/msphere.00709-24","DOIUrl":"10.1128/msphere.00709-24","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Existing genetic classification systems for porcine reproductive and respiratory syndrome virus type 2 (PRRSV-2), such as restriction fragment length polymorphisms and sub-lineages, are unreliable indicators of close genetic relatedness or lack sufficient resolution for epidemiological monitoring routinely conducted by veterinarians. Here, we outline a fine-scale classification system for PRRSV-2 genetic variants in the United States. Based on &gt;25,000 U.S. open reading frame 5 (ORF5) sequences, sub-lineages were divided into genetic variants using a clustering algorithm. Through classifying new sequences every 3 months and systematically identifying new variants across 8 years, we demonstrated that prospective implementation of the variant classification system produced robust, reproducible results across time and can dynamically accommodate new genetic diversity arising from virus evolution. From 2015 to 2023, 118 variants were identified, with ~48 active variants per year, of which 26 were common (detected &gt;50 times). Mean within-variant genetic distance was 2.4% (max: 4.8%). The mean distance to the closest related variant was 4.9%. A routinely updated webtool (https://stemma.shinyapps.io/PRRSLoom-variants/) was developed and is publicly available for end users to assign newly generated sequences to a variant ID. This classification system relies on U.S. sequences from 2015 onward; further efforts are required to extend this system to older or international sequences. Finally, we demonstrate how variant classification can better discriminate between previous and new strains on a farm, determine possible sources of new introductions into a farm/system, and track emerging variants regionally. Adoption of this classification system will enhance PRRSV-2 epidemiological monitoring, research, and communication, and improve industry responses to emerging genetic variants.IMPORTANCEThe development and implementation of a fine-scale classification system for PRRSV-2 genetic variants represent a significant advancement for monitoring PRRSV-2 occurrence in the swine industry. Based on systematically applied criteria for variant identification using national-scale sequence data, this system addresses the shortcomings of existing classification methods by offering higher resolution and adaptability to capture emerging variants. This system provides a stable and reproducible method for classifying PRRSV-2 variants, facilitated by a freely available and regularly updated webtool for use by veterinarians and diagnostic labs. Although currently based on U.S. PRRSV-2 ORF5 sequences, this system can be expanded to include sequences from other countries, paving the way for a standardized global classification system. By enabling accurate and improved discrimination of PRRSV-2 genetic variants, this classification system significantly enhances the ability to monitor, research, and respond to PRRSV-2 outbreaks, ultimately supporting better management and cont","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0070924"},"PeriodicalIF":3.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024152","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":"mSphere of Influence: The challenge of screening for essential protein kinases in <i>Trypanosoma cruzi</i>.","authors":"Miguel A Chiurillo","doi":"10.1128/msphere.00598-24","DOIUrl":"10.1128/msphere.00598-24","url":null,"abstract":"<p><p>Miguel Chiurillo works in the field of protein kinases, studying their role in cell signaling and cell cycle progression in <i>Trypanosoma cruzi</i>. In this mSphere of Influence article, he reflects on how the research articles \"Systematic functional analysis of <i>Leishmania</i> protein kinases identifies regulators of differentiation or survival\" by Baker et al. and \"Screening the <i>Toxoplasma</i> kinome with high throughput tagging identifies a regulator of invasion and egress\" by Smith et al. made an impact on his understanding of the complexity of the <i>Trypanosoma cruzi</i> kinome and the challenges to unravel it.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0059824"},"PeriodicalIF":3.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053021","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":"Structural analysis of extracellular ATP-independent chaperones of streptococcal species and protein substrate interactions.","authors":"Charles Agbavor, Madeline Torres, Nicole L Inniss, Sarah Latimer, George Minasov, Ludmilla Shuvalova, Zdzislaw Wawrzak, Dominika Borek, Zbyszek Otwinowski, Peter J Stogios, Alexei Savchenko, Wayne F Anderson, Karla J F Satchell, Laty A Cahoon","doi":"10.1128/msphere.01078-24","DOIUrl":"10.1128/msphere.01078-24","url":null,"abstract":"&lt;p&gt;&lt;p&gt;During infection, bacterial pathogens rely on secreted virulence factors to manipulate the host cell. However, in gram-positive bacteria, the molecular mechanisms underlying the folding and activity of these virulence factors after membrane translocation are not clear. Here, we solved the protein structures of two secreted parvulin and two secreted cyclophilin-like peptidyl-prolyl isomerase (PPIase) ATP-independent chaperones found in gram-positive streptococcal species. The extracellular parvulin-type PPIase, PrsA in &lt;i&gt;Streptococcus pneumoniae&lt;/i&gt; and &lt;i&gt;Streptococcus mutans&lt;/i&gt; maintain dimeric crystal structures reminiscent of folding catalysts that consist of two domains, a PPIase and foldase domain. Structural comparison of the two cyclophilin-like extracellular chaperones from &lt;i&gt;S. pneumoniae&lt;/i&gt; and &lt;i&gt;Streptococcus pyogenes&lt;/i&gt; with other cyclophilins demonstrates that this group of cyclophilin-like chaperones has novel structural appendages formed by 9- and 24-residue insertions. Furthermore, we demonstrate that deletion of &lt;i&gt;prsA&lt;/i&gt; and &lt;i&gt;slrA&lt;/i&gt; genes impairs the secretion of the cholesterol-dependent pore-forming toxin, pneumolysin in &lt;i&gt;S. pneumoniae&lt;/i&gt;. Using protein pull-down and biophysical assays, we demonstrate a direct interaction between PrsA and SlrA with Ply. Then, we developed chaperone-assisted folding assays that show that the &lt;i&gt;S. pneumoniae&lt;/i&gt; PrsA and SlrA extracellular chaperones accelerate pneumolysin folding. In addition, we demonstrate that SlrA and, for the first time, &lt;i&gt;S. pyogene&lt;/i&gt;s PpiA exhibit PPIase activity and can bind the immunosuppressive drug, cyclosporine A. Altogether, these findings suggest a mechanistic role for streptococcal PPIase chaperones in the activity and folding of secreted virulence factors such as pneumolysin.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Streptococcal species are a leading cause of lower respiratory infections that annually affect millions of people worldwide. During infection, streptococcal species secrete a medley of virulence factors that allow the bacteria to colonize and translocate to deeper tissues. In many gram-positive bacteria, virulence factors are secreted from the cytosol across the bacterial membrane in an unfolded state. The bacterial membrane-cell wall interface is exposed to the potentially harsh extracellular environment, making it difficult for native virulence factors to fold before being released into the host. ATP-independent PPIase-type chaperones, PrsA and SlrA, are thought to facilitate folding and stabilization of several unfolded proteins to promote the colonization and spread of streptococci. Here, we present crystal structures of the molecular chaperones of PrsA and SlrA homologs from streptococcal species. We provide evidence that the &lt;i&gt;Streptococcus pyogenes&lt;/i&gt; SlrA homolog, PpiA, has PPIase activity and binds to cyclosporine A. In addition, we show that &lt;i&gt;Streptococcus pneumoniae&lt;/i&gt; PrsA and SlrA directly interact and fold the ch","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0107824"},"PeriodicalIF":3.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059866","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":"mSphere of Influence: How the single cell contributes to the collective.","authors":"Gina R Lewin","doi":"10.1128/msphere.00431-24","DOIUrl":"10.1128/msphere.00431-24","url":null,"abstract":"<p><p>Gina Lewin works in the field of microbial ecology, with a focus on the human microbiota. In this mSphere of Influence article, she reflects on how two papers describing bacterial single-cell RNA-seq-\"Prokaryotic single-cell RNA sequencing by <i>in situ</i> combinatorial indexing\" by S. B. Blattman, W. Jiang, P. Oikonomou, and S. Tavazoie (Nat Microbiol 5:1192-1201, 2020, https://doi.org/10.1038/s41564-020-0729-6) and \"Microbial single-cell RNA sequencing by split-pool barcoding\" by A. Kuchina, L. M. Brettner, L. Paleologu, C. M. Roco, et al. (Science 371:eaba5257, 2021, https://doi.org/10.1126/science.aba5257)-impacted her work by developing a new approach to study how single cells of bacteria contribute to ecosystem-level processes.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0043124"},"PeriodicalIF":3.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807030","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":"Combined mutations in nonstructural protein 14, envelope, and membrane proteins mitigate the neuropathogenicity of SARS-CoV-2 Omicron BA.1 in K18-hACE2 mice.","authors":"Kotou Sangare, Shufeng Liu, Prabhuanand Selvaraj, Charles B Stauft, Matthew F Starost, Tony T Wang","doi":"10.1128/msphere.00726-24","DOIUrl":"10.1128/msphere.00726-24","url":null,"abstract":"<p><p>We previously reported that mutations outside the spike protein play a role in the attenuation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.1 variant in human ACE2 transgenic mice (K18-hACE2). Here, we assessed the pathogenicity of SARS-CoV-2 (WA1/2020) containing mutations from the Omicron BA.1 variant in K18-hACE2 mice. At an infection dose of 10⁴ plaque-forming units (PFU), WA1 virus carrying Omicron BA.1 Nsp14(I42V), E(T9I), M(D3G/Q19E/A63T), but not Nsp6(Δ105-107, I189V), substitutions showed significant reduction in lethality. Interestingly, reduction of viral load is more pronounced in the brains than in the lungs. Subsequent analyses suggest that BA.1 E(T9I) and M(D3G/Q19E/A63T) substitutions result in less efficient packaging of virus-like particles. Given that Nsp14(I42V), E(T9I), M(Q19E/A63T) are well preserved in subsequent omicron subvariants, including currently circulating variants, our findings highlight the importance of understanding how non-spike mutations affect the pathogenicity of SARS-CoV-2 variants.</p><p><strong>Importance: </strong>Inoculation of transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) with SARS-CoV-2 often leads to a fatal brain infection. Omicron BA.1 variant, however, was found to be non-lethal in this model. Here, we systematically assessed the effect of individual mutations of Omicron BA.1 on the pathogenicity of the virus in hACE2 transgenic mice and found that combination of 5 mutations of Nsp14, E, and M of BA.1 variant significantly lowered brain viral load and reduced lethality. These results provide new insights into how SARS-CoV-2 Omicron BA.1 is attenuated.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0072624"},"PeriodicalIF":3.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807864","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}