mSpherePub Date : 2025-03-25Epub Date: 2025-02-26DOI: 10.1128/msphere.00556-24
Stephanie N Langel
{"title":"mSphere of Influence: The maternal gut-mammary axis and its role in shaping neonatal health.","authors":"Stephanie N Langel","doi":"10.1128/msphere.00556-24","DOIUrl":"10.1128/msphere.00556-24","url":null,"abstract":"<p><p>Stephanie Langel works in the field of breast milk immunity and maternal-neonatal health. In this mSphere of Influence article, she reflects on how three pivotal papers-Roux et al. (J Exp Med 146:1311-1322, 1977, https://doi.org/10.1084/jem.146.5.1311), Wilson and Butcher (J Exp Med 200:805-809, 2004, https://doi.org/10.1084/jem.20041069), and Rogier et al. (Proc Natl Acad Sci USA 111:3074-3079, 2014, https://doi.org/10.1073/pnas.1315792111)-made an impact on her by uncovering the critical pathways and mechanisms through which gut-derived IgA-secreting cells migrate to the mammary gland and secrete antibodies against intestinal microbes. These foundational studies shaped her understanding of the gut-mammary axis and continue to inspire her research aimed at advancing maternal and neonatal health through breast milk immunology.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0055624"},"PeriodicalIF":3.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143502864","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}
mSpherePub Date : 2025-03-25Epub Date: 2025-02-28DOI: 10.1128/msphere.00941-24
Zhao Wang, Yanbai Wang, Shulong Yang, Zhenhai Wang, Qian Yang
{"title":"<i>Brucella suis</i> S2 strain inhibits IRE1/caspase-12/caspase-3 pathway-mediated apoptosis of microglia HMC3 by affecting the ubiquitination of CALR.","authors":"Zhao Wang, Yanbai Wang, Shulong Yang, Zhenhai Wang, Qian Yang","doi":"10.1128/msphere.00941-24","DOIUrl":"10.1128/msphere.00941-24","url":null,"abstract":"<p><p>Neurobrucellosis represents a severe complication of brucellosis, posing a considerable risk to human health and quality of life. This condition arises from an increased susceptibility to chronic <i>Brucella</i> infection, a significant clinical challenge. One key factor contributing to chronic neurobrucellosis is the regulation of microglial apoptosis by <i>Brucella</i>; however, the exact molecular mechanisms remain largely unresolved. In this study, human microglial clone 3 (HMC3) cells were infected with <i>Brucella suis</i> vaccine strain S2 (<i>B. suis</i> S2) at varying multiplicity of infection (MOI) and durations to assess its effects on the IRE1/caspase-12/caspase-3 signaling pathway. Following the suppression of this pathway by <i>B. suis</i> S2, calreticulin (CALR) was identified through ubiquitin-modified proteomics (data accessible via ProteomeXchange, identifier PXD056006). To further investigate, CALR-overexpression and knockdown HMC3 cell lines were infected with <i>B. suis</i> S2 to elucidate the mechanism by which <i>B. suis</i> S2 inhibits apoptosis in HMC3 cells. In conclusion, our findings demonstrate that <i>B. suis</i> S2 suppresses HMC3 cell apoptosis via the IRE1/caspase-12/caspase-3 pathway by modulating CALR ubiquitination. This study provides a theoretical basis for exploring the mechanisms of neurobrucellosis and offers insights into its clinical treatment.IMPORTANCENeurobrucellosis is a severe complication impacting the central nervous system (CNS) due to neurological deficits caused by <i>Brucella</i>, with primary clinical features including meningitis, encephalitis, brain abscesses, and demyelinating lesions. These nonspecific symptoms often lead to misdiagnosis or delayed diagnosis, increasing the risk of recurrent or chronic neurobrucellosis infections. Consequently, persistent infection and relapse are critical challenges in the clinical management of neurobrucellosis, which are closely linked to <i>Brucella</i>'s survival and replication within microglia. Interestingly, <i>Brucella</i> may inhibit microglia apoptosis by mitigating endoplasmic reticulum (ER) stress, though the precise molecular mechanisms remain largely unexplored. Thus, this study will elucidate the specific mechanisms by which <i>Brucella</i> suppresses microglial apoptosis and provide deeper insights into the molecular pathogenesis and clinical treatment of neurobrucellosis.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0094124"},"PeriodicalIF":3.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523897","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}
mSpherePub Date : 2025-03-25Epub Date: 2025-02-27DOI: 10.1128/msphere.00118-25
Patrick D Schloss
{"title":"A call for healing and unity.","authors":"Patrick D Schloss","doi":"10.1128/msphere.00118-25","DOIUrl":"10.1128/msphere.00118-25","url":null,"abstract":"","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0011825"},"PeriodicalIF":3.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516139","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}
mSpherePub Date : 2025-03-25Epub Date: 2025-02-21DOI: 10.1128/msphere.01014-24
Ana Catarina Duarte, Lucía Fernández, Ana Rodríguez, Pilar García
{"title":"A new bacteriophage infecting <i>Staphylococcus epidermidis</i> with potential for removing biofilms by combination with chimeric lysin CHAPSH3b and vancomycin.","authors":"Ana Catarina Duarte, Lucía Fernández, Ana Rodríguez, Pilar García","doi":"10.1128/msphere.01014-24","DOIUrl":"10.1128/msphere.01014-24","url":null,"abstract":"<p><p><i>Staphylococcus epidermidis</i> is the cause of serious skin and prosthetic joint infections despite being a common inhabitant of human body surfaces. However, both the rise in antibiotic resistance in this species and its ability to form biofilms are increasingly limiting the available therapeutic options against these illnesses. In this landscape, phage therapy stands out as an interesting alternative to antibiotics. In the present study, we report the isolation and characterization of a novel virulent phage infecting <i>S. epidermidis</i> (<i>Staphylococcus</i> phage IPLA-AICAT), which belongs to the <i>Herelleviridae</i> family. The estimated genome size of this virus is 139,941 bp, and sequence analysis demonstrated the absence of antibiotic resistance genes and virulence factors. This phage infects a high proportion (79%) of clinically relevant <i>S. epidermidis</i> strains and exhibits antibiofilm activity. Moreover, a combination of this phage with other antimicrobials, i.e., vancomycin and the lytic protein CHAPSH3b, further improved the reduction in surface-attached bacteria. Notably, the combination of <i>Staphylococcus</i> phage IPLA-AICAT (10<sup>9</sup> PFU/mL) and CHAPSH3b (8 µM), originally designed to target <i>Staphylococcus aureus</i>, was able to reduce the number of viable cells by 3.06 log units in 5-h-old biofilms. In 24-h-old biofilms, the reduction was also significant after 6 h of treatment (2.06 log units) and 24 h of treatment (2.52 log units). These results confirm our previous data regarding the potential of phage-lysin mixtures against staphylococcal biofilms.IMPORTANCE<i>Staphylococcus epidermidis</i> is one of the main causes to device-associated infections mostly due to its ability to form stable biofilms attached to human tissues. Besides the inherent antimicrobial tolerance of biofilms, this microorganism is also increasingly becoming resistant to standard-of-care antibiotics. To fight against this problem, phage therapy is a viable option to complement the available antibiotics in the treatment of recalcitrant infections. This work describes a new phage infecting <i>S. epidermidis</i> clinical strains that is a member of the <i>Herelleviridae</i> family and the combination with other antimicrobials to further improve the reduction of biofilms. Together with the significant progress achieved in the development of diagnostic tools, phages and their derived proteins will bring us much closer to a therapeutic landscape in which we are not so heavily reliant on antibiotics to combat bacterial pathogens.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0101424"},"PeriodicalIF":3.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468579","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}
mSpherePub Date : 2025-03-25Epub Date: 2025-02-21DOI: 10.1128/msphere.00651-24
Andrew J M Swafford
{"title":"mSphere of Influence: Fungal behavior as a framework for the evolution of emergent traits.","authors":"Andrew J M Swafford","doi":"10.1128/msphere.00651-24","DOIUrl":"10.1128/msphere.00651-24","url":null,"abstract":"<p><p>Andrew Swafford works in the field of evolutionary cell biology. In this mSphere of Influence article, he reflects on how the simultaneous introduction to the evolution of vision, the sensory biology of chytrid fungi, and a classic paper by Vrba and Gould helped shape his thinking about sensory evolution.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0065124"},"PeriodicalIF":3.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468602","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}
mSpherePub Date : 2025-03-25Epub Date: 2025-02-24DOI: 10.1128/msphere.01092-24
Sai Luo, Ya-Ting Wang
{"title":"First-ever ASM Global Research Symposium on Microbes in Human Health in Tsinghua, Beijing, China.","authors":"Sai Luo, Ya-Ting Wang","doi":"10.1128/msphere.01092-24","DOIUrl":"10.1128/msphere.01092-24","url":null,"abstract":"<p><p>The American Society for Microbiology Global Research Symposium on Microbes in Human Health, hosted in partnership with Tsinghua University, was held in Beijing, China, on 25 to 27 September 2024. The conference provided an international forum for microbiologists from different disciplines to present and discuss new findings. The meeting covered a wide range of topics, spanning across bacteria, virus, fungi, and hosts. This report summarizes the presentations and emerging themes.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0109224"},"PeriodicalIF":3.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483717","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":"Estimated size of the total genome and protein space of viruses.","authors":"Congyu Lu, Yifan Wu, Zheng Zhang, Longfei Mao, Xingyi Ge, Aiping Wu, Fengzhu Sun, Yongqiang Jiang, Yousong Peng","doi":"10.1128/msphere.00683-24","DOIUrl":"10.1128/msphere.00683-24","url":null,"abstract":"<p><p>Recent metagenomic studies have identified a vast number of viruses. However, the systematic assessment of the true genetic diversity of the whole virus community on our planet remains to be investigated. Here, we explored the genome and protein space of viruses by simulating the process of virus discovery in viral metagenomic studies. Among multiple functions, the power function was found to best fit the increasing trends of virus diversity and was, therefore, used to predict the genetic space of viruses. The estimate suggests that there are at least 8.23e+08 viral operational taxonomic units and 1.62e+09 viral protein clusters on Earth when assuming the saturation of the virus genetic space, taking into account the balance of costs and the identification of novel viruses. It is noteworthy that less than 3% of the viral genetic diversity has been uncovered thus far, emphasizing the vastness of the unexplored viral landscape. To saturate the genetic space, a total of 3.08e+08 samples would be required. Analysis of viral genetic diversity by ecosystem yielded estimates consistent with those mentioned above. Furthermore, the estimate of the virus genetic space remained robust when accounting for the redundancy of sampling, sampling time, sequencing platform, and parameters used for protein clustering. This study provides a guide for future sequencing efforts in virus discovery and contributes to a better understanding of viral diversity in nature.IMPORTANCEViruses are the most abundant and diverse biological entities on Earth. In recent years, a large number of viruses have been discovered based on sequencing technology. However, it is not clear how many kinds of viruses exist on Earth. This study estimates that there are at least 823 million types of viruses and 1.62 billion types of viral proteins. Remarkably, less than 3% of this large diversity has been uncovered to date. These findings highlight the enormous potential for discovering new viruses and reveal a significant gap in our current understanding of the viral world. This study calls for increased attention and resources to be directed toward viral discovery and metagenomics and provides a guide for future sequencing efforts, enhancing our knowledge of viral diversity in nature for ecology, biology, and public health.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0068324"},"PeriodicalIF":3.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492975","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}
mSpherePub Date : 2025-03-25Epub Date: 2025-02-07DOI: 10.1128/msphere.00531-24
Jigar V Desai
{"title":"mSphere of Influence: Complement activity beyond systemic circulation-implications in the context of infections.","authors":"Jigar V Desai","doi":"10.1128/msphere.00531-24","DOIUrl":"10.1128/msphere.00531-24","url":null,"abstract":"<p><p>Jigar V. Desai works in the field of immunology, studying the mucosal and systemic complement systems and their roles in regulating the immune response. In this mSphere of Influence article, he reflects on how the papers by the Kemper, Kulkarni, and Kasper laboratories made an impact on his ongoing work investigating the cell-intrinsic and extrinsic regulation of complement and studying its impacts on mucosal and systemic immunity.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0053124"},"PeriodicalIF":3.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365289","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}
mSpherePub Date : 2025-03-25Epub Date: 2025-02-26DOI: 10.1128/msphere.00907-24
Hyun Young Kim, Christina M Rothenberger, Mary E Davey, Manda Yu
{"title":"Antibodies with specificity to glycan motifs that decorate OMV cargo proteins.","authors":"Hyun Young Kim, Christina M Rothenberger, Mary E Davey, Manda Yu","doi":"10.1128/msphere.00907-24","DOIUrl":"10.1128/msphere.00907-24","url":null,"abstract":"<p><p><i>Porphyromonas gingivalis</i> is a major etiological agent of periodontal disease, and infections with this bacterium are associated with systemic pathologies, including atherosclerosis, rheumatoid arthritis, and Alzheimer's disease. <i>P. gingivalis</i> has a variety of immune evasion mechanisms and exhibits highly variable cell surface characteristics that are strain dependent, complicating the development of effective vaccines and therapeutics. Here, we show that a subset of immunoglobulin M (IgM) antibodies in antiserum raised against <i>P. gingivalis</i> strain W83 selectively recognize the outer membrane vesicles (OMVs). Pre-adsorption with a mutant strain lacking an OMV-specific lipoprotein (PG1881) that has been shown to be glycosylated significantly enhanced IgM specificity toward PG1881 and the OMVs. In addition, the IgM reactivity against the OMVs derived from a mutant lacking enzymes required for O-glycosylation was markedly reduced, indicating that the IgM targets the glycan motifs on proteins carried on OMVs. Importantly, the IgM exhibited specific recognition of OMVs from both <i>P. gingivalis</i> and <i>Porphyromonas endodontalis</i>, while showing low reactivity toward other genera belonging to the phylum Bacteroidetes. This study revealed a potential host evasion strategy and highlights the potential for utilizing O-glycans in vaccine development and OMV-targeted antibodies in therapeutic interventions to combat <i>P. gingivalis</i> infections.</p><p><strong>Importance: </strong>O-glycosylation of cell surface proteins by bacteria is known to play a role in various functions including colonization and immune evasion. This study highlights the identification of IgM antibodies that specifically recognize O-glycosylated proteins that are selectively carried on outer membrane vesicles (OMVs). The findings suggest a potential host evasion mechanism and open new avenues for using OMVs in vaccine development and targeting O-glycans with antibodies as a therapeutic strategy against the subgingival pathobiont <i>P. gingivalis</i>.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0090724"},"PeriodicalIF":3.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143502861","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}
mSpherePub Date : 2025-03-25Epub Date: 2025-02-26DOI: 10.1128/msphere.00611-24
Luisa Berná
{"title":"mSphere of Influence: <i>Trypanosoma cruzi</i> genome in 3D action.","authors":"Luisa Berná","doi":"10.1128/msphere.00611-24","DOIUrl":"10.1128/msphere.00611-24","url":null,"abstract":"<p><p>Luisa Berná works in the field of comparative and evolutionary genomics in unicellular eukaryotes. In this mSphere of Influence article, she reflects on how advances in three-dimensional genome organization have reshaped our understanding of parasite biology. She discusses how recent findings uncover the distinctiveness of the three-dimensional architecture of <i>Trypanosoma cruzi'</i>s genome and its functional implications. Berná argues that integrating structural genomics into parasite research is essential for advancing our understanding of genome organization and its role in shaping parasite biology, particularly in the context of neglected tropical diseases.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0061124"},"PeriodicalIF":3.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143502863","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}