mSphere最新文献

{"title":"The essential kinase TgGSK regulates centrosome segregation and endodyogeny in <i>Toxoplasma gondii</i>.","authors":"Amanda Krueger, Sofia Horjales, Chunlin Yang, William J Blakely, Maria E Francia, Gustavo Arrizabalaga","doi":"10.1128/msphere.00111-25","DOIUrl":"10.1128/msphere.00111-25","url":null,"abstract":"<p><p>Intracellular replication is crucial for the success of apicomplexan parasites, including <i>Toxoplasma gondii</i>. Therefore, essential players in parasite replication represent potential targets for drug development. We have characterized TgGSK, a glycogen synthase kinase homolog that plays an important role in <i>Toxoplasma</i> endodyogeny. We have shown that TgGSK has a dynamic localization that is concurrent with the cell cycle. In non-dividing parasites, this kinase is highly concentrated in the nucleus. However, during division, TgGSK displays a cytosolic localization, with concentration foci at the centrosomes, a key organelle involved in parasite division, and the basal end. Conditional knockdown of TgGSK determined that it is essential for the completion of the lytic cycle and proper parasite division. Parasites lacking endogenous protein levels of TgGSK exhibited defects in division synchronicity and the segregation of the nucleus and apicoplast into forming daughter cells. These phenotypes are associated with defects in centrosome duplication and fission. Global phosphoproteomic analysis determined TgGSK-dependent phosphorylation of RNA-processing, basal end, and centrosome proteins. Consistent with the putative regulation of RNA-processing proteins, global transcriptomic analysis suggests that TgGSK is needed for proper splicing. Finally, we show that TgGSK interacts with GCN5b, a well-characterized acetyltransferase with roles in transcriptional control. Conversely, GCN5b chemical inhibition results in specific degradation of TgGSK. Thus, these studies reveal the involvement of TgGSK in various crucial processes, including endodyogeny and splicing, and identify acetylation as a possible mechanism by which this essential kinase is regulated.</p><p><strong>Importance: </strong>While infection with the parasite <i>Toxplasma gondii</i> is largely asymptomatic in healthy adults, severe disease and death can result in immunocompromised individuals and in those infected congenitally. With minimal treatments for toxoplasmosis available, it is crucial to study parasite-specific processes to identify new drug targets. This study investigated the protein TgGSK, uncovering its essentiality for parasite proper division and survival. We performed an in-depth study of the functional role of this kinase. Importantly, TgGSK was shown to bear higher homology to plant proteins than its mammalian counterparts, which may allow for specific targeting of this protein.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0011125"},"PeriodicalIF":3.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731032","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":"Seasonality and dynamics of schistosomiasis in the environment: usefulness of environmental DNA (eDNA) surveillance system at a community level for risk mapping schistosomiasis in Ekiran Village, Leyte, Philippines.","authors":"Mark June Revolteado, Marcello Otake Sato, Joseph Valencia, Mario Jiz, Eleonor Cervantes, Ralph Aniceto, Marianette Inobaya, Darren Gray, Catherine A Gordon, Pengfei Cai, Yasuhito Sako, Megumi Sato","doi":"10.1128/msphere.01061-24","DOIUrl":"https://doi.org/10.1128/msphere.01061-24","url":null,"abstract":"<p><p>Schistosomiasis, primarily caused by <i>Schistosoma japonicum</i> (Sj) in Asia, remains a major health concern in the Philippines, affecting 12.4 million people and causing symptoms like fever, abdominal pain, and hepatosplenomegaly. Chronic disease leads to stunting in children, and reinfection persists despite efforts to reduce morbidity. Current strategies focused on mass drug administration (MDA) and sporadic snail surveys, leaving gaps in monitoring and mitigating schistosomiasis transmission in the environment. To address these issues, this study refined an environmental DNA (eDNA)-based qualitative real-time polymerase chain reaction assay by making it field-applicable and multiplex, to detect both the parasite <i>S. japonicum</i> and its intermediate snail host, <i>Oncomelania hupensis quadrasi</i> (Ohq), using water samples. We surveyed the 30 sentinel sites quarterly-from July 2023 to March 2024-in Ekiran Village, Alangalang, Leyte, Philippines. Collectively, the eDNA of <i>O.h. quadrasi</i> was detected in 18 sites and that of <i>S. japonicum</i> eDNA was detected in 16 sites, while direct snail observation confirmed the presence in only five sites, with infected snails found in only one site. Consequently, the assay described temporal variation of Ohq and Sj, revealing the dynamics of Ohq colonies and Sj in Ekiran's water sources. The eDNA confirmed the focality of Ohq and showed the erratic presence of Sj. Interestingly, both target species' eDNA was observed more during the rainy season (December and March), which suggests a higher infection probability during this period. Integrating eDNA detection system with the existing control programs will enhance the identification of transmission hotspots, which may aid in reducing exposure risk for both humans and animals in the endemic areas.</p><p><strong>Importance: </strong>This study aimed to fill the gaps in monitoring and mitigating schistosomiasis transmission in the environment. This field-applicable environmental DNA (eDNA)-based qualitative real-time polymerase chain reaction (qPCR) detection system focused on effectively detecting <i>Schistosoma japonicum</i> and its snail intermediate host, <i>Oncomelania hupensis quadrasi</i>, at the community level, moving from the traditional detection methods that are labor-intensive, less sensitive, and exposing surveyors to potential risk of infection. By introducing a field-applicable eDNA-based qPCR assay, this research provides a sensitive, non-invasive, and rapid molecular method for detecting <i>S. japonicum</i> and <i>O.h. quadrasi</i> in the environment. Additionally, the study not only provided insights in enhanced surveillance strategies but also contributed to a holistic eco-health approach by generating hazard maps for potential transmission and contamination sites, which could improve future control efforts and resource allocation for schistosomiasis elimination.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0106124"},"PeriodicalIF":3.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710685","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":"Reply to Nachamkin, \"Diversity of <i>Campylobacter</i> species in a rhesus macaque breeding colony\".","authors":"Rebecca L Bacon, Carolyn L Hodo, Sara D Lawhon","doi":"10.1128/msphere.00041-25","DOIUrl":"https://doi.org/10.1128/msphere.00041-25","url":null,"abstract":"","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0004125"},"PeriodicalIF":3.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701126","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":"BALF editome profiling reveals A-to-I RNA editing associated with severity and complications of <i>Mycoplasma pneumoniae</i> pneumonia in children.","authors":"Yun-Yun Jin, Yun Guo, Su-Wan Xiong, Na Zhang, Jian-Huan Chen, Feng Liu","doi":"10.1128/msphere.01012-24","DOIUrl":"10.1128/msphere.01012-24","url":null,"abstract":"<p><p><i>Mycoplasma pneumoniae</i> is an important human respiratory pathogen that causes mild-to-moderate community-acquired <i>M. pneumoniae</i> pneumonia (MPP), particularly in children. RNA editing plays a vital role in pathogen infection and host immune response, but it remains largely unknown how it could be involved in the epigenetic regulation of host response to <i>M. pneumoniae</i> infection. In the present study, we performed an epitranscriptomic analysis of adenosine to inosine (A-to-I) editing in 39 bronchoalveolar lavage fluid (BALF) samples from the severe side (SS) and the opposite side (OS) of patients with MPP. Our editome profiling identified 87 differential RNA editing (DRE) events in 50 genes, especially missense editing events that recoded C-C motif chemokine receptor-like 2 (<i>CCRL2</i>, p.K147R) and cyclin I (<i>CCNI</i>, p.R75G). The expression of adenosine deaminase acting on RNA (<i>ADAR</i>) significantly increased on SS compared to OS and positively correlated with the average RNA editing level and individual DRE events. Meanwhile, functional enrichment analysis showed that DRE was observed in genes primarily associated with the negative regulation of innate immune response, type I interferon production, and cytokine production. Further comparison of SS between complicated MPP (CMPP) and non-complicated MPP (NCMPP) revealed RNA editing events associated with MPP complications, with a higher <i>ADAR</i> expression in CMPP than NCMPP. By identifying DRE events as biomarkers associated with MPP severity and complications, our editome profiling provides new insight into the potential role played by A-to-I RNA editing in modulating the host's immune system during <i>M. pneumoniae</i> infection.IMPORTANCEOur research investigates how <i>Mycoplasma pneumoniae</i>, a common respiratory pathogen, influences how our cells modify their genetic instructions. By studying RNA editing changes in bronchoalveolar lavage fluid from patients with <i>M. pneumoniae</i> pneumonia, we aim to investigate how <i>M. pneumoniae</i> infection alters epigenetics and contributes to the disease severity and complications. Understanding such epigenetic alterations not only sheds light on the mechanisms underlying <i>M. pneumoniae</i> infection but also holds potential implications for developing better diagnostic tools and therapies. Ultimately, this work may facilitate the design of more targeted treatments to alleviate the impact of respiratory infections caused by the pathogen. Our findings may also offer broader insights into how microbial infections reshape immune processes, highlighting the importance of RNA editing in host-pathogen interactions.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0101224"},"PeriodicalIF":3.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492973","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":"Exploring the differential localization of protein kinase A isoforms in <i>Candida albicans</i>.","authors":"Saif Hossain, Zhongle Liu, Nicole Robbins, Leah E Cowen","doi":"10.1128/msphere.01037-24","DOIUrl":"10.1128/msphere.01037-24","url":null,"abstract":"<p><p>The cAMP-dependent protein kinase A (PKA) plays important roles in a wide range of biological processes in eukaryotic organisms. In the fungal pathogen <i>Candida albicans</i>, PKA is a critical regulator of morphological transitions, which are a key virulence trait. PKA is composed of two catalytic isoforms, Tpk1 and Tpk2, which are often thought to act together in a complex with the regulatory subunit Bcy1. Although Tpk1 and Tpk2 have some redundant functions, they also have distinct cellular functions for which the mechanistic underpinnings remain largely elusive. Here, we constructed functional GFP-tagged fusion proteins for Tpk1, Tpk2, and Bcy1 to explore the localization of PKA isoforms. We observed that the PKA holoenzyme is mainly found in the cytoplasm, as Bcy1 is always excluded from the nucleus. Under glucose-replete conditions, both Tpk1 and Tpk2 translocate into the nucleus from the cytosol. In the presence of glycerol, Tpk1 resides in the cytosol, whereas Tpk2 and Bcy1 become enriched on the vacuolar membrane. As the C-terminal domains of Tpk are highly homologous, we investigated the localization and function of hybrid Tpk proteins with exchanged N-terminal domains. We found the catalytic C-terminus of Tpk1 is required for morphogenesis in solid medium, whereas the C-terminus of Tpk2 is critical for filamentation in liquid. Interestingly, the N-terminus of Tpk2 drives its localization to the vacuolar membrane. Our work highlights environmentally contingent localization patterns for the PKA subunits and suggests that the nuclear localization of Tpk is not sufficient to induce the filamentation program in a leading fungal pathogen of humans.IMPORTANCEFungal pathogens have a devastating impact on human health worldwide. They infect billions of people and kill more than 2.5 million per year. <i>Candida albicans</i> is a leading human fungal pathogen responsible for causing life-threatening systemic disease in immunocompromised individuals. A key virulence trait in <i>C. albicans</i> is the ability to switch between yeast and filamentous forms. The conserved protein kinase A (PKA) regulates diverse functions in the cell, including growth and filamentation. Although PKA has been studied in <i>C. albicans</i> for decades, the subcellular localization of PKA has not been thoroughly investigated. Here, we constructed functional GFP-tagged PKA subunits to explore their localization. We identified differential localization patterns for the PKA subunits that are carbon-source dependent and report that these proteins localize into foci in response to diverse environmental stresses. These findings further our understanding of a critical regulator of growth and virulence in <i>C. albicans</i>.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0103724"},"PeriodicalIF":3.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492977","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":"The role of l-serine and l-threonine in the energy metabolism and nutritional stress response of <i>Trypanosoma cruzi</i>.","authors":"Mayke Bezerra Alencar, Richard Marcel Bruno Moreira Girard, Marcell Crispim, Carlos Gustavo Baptista, Marc Biran, Frederic Bringaud, Ariel Mariano Silber","doi":"10.1128/msphere.00983-24","DOIUrl":"10.1128/msphere.00983-24","url":null,"abstract":"&lt;p&gt;&lt;p&gt;l-Serine and l-threonine have versatile roles in metabolism. In addition to their use in protein synthesis, these amino acids participate in the biosynthesis pathways of other amino acids and even phospholipids. Furthermore, l-serine and l-threonine can be substrates for a serine/threonine dehydratase (Ser/ThrDH), resulting in pyruvate and 2-oxobutyrate, respectively, thus being amino acids with anaplerotic potential. &lt;i&gt;Trypanosoma cruzi&lt;/i&gt;, the etiological agent of Chagas disease, uses amino acids in several biological processes: metacyclogenesis, infection, resistance to nutritional and oxidative stress, osmotic control, etc. This study investigated the import and metabolism of l-serine, l-threonine, and glycine in &lt;i&gt;T. cruzi&lt;/i&gt;. Our results demonstrate that these amino acids are transported from the extracellular environment into &lt;i&gt;T. cruzi&lt;/i&gt; cells through a saturable transport system that fits the Michaelis-Menten model. Our results show that l-serine and l-threonine can sustain epimastigote cell viability under nutritional stress conditions and stimulate oxygen consumption, maintaining intracellular ATP levels. Additionally, our findings indicate that serine plays a role in establishing the mitochondrial membrane potential in &lt;i&gt;T. cruzi&lt;/i&gt;. Serine is also involved in energy metabolism via the serine-pyruvate pathway, which stimulates the production and subsequent excretion of acetate and alanine. Our results demonstrate the importance of l-serine and l-threonine in the energy metabolism of &lt;i&gt;T. cruzi&lt;/i&gt; and provide new insights into the metabolic adaptations of this parasite during its life cycle.IMPORTANCE&lt;i&gt;Trypanosoma cruzi&lt;/i&gt;, the parasite responsible for Chagas disease, impacts 5-6 million individuals in the Americas and is rapidly spreading globally due to significant human migration. This parasitic organism undergoes a complex life cycle involving triatomine insects and mammalian hosts, thriving in diverse environments, such as various regions within the insect's digestive tract and mammalian cell cytoplasm. Crucially, its transmission hinges on its adaptive capabilities to varying environments. One of the most challenging environments is the insect's digestive tract, marked by nutrient scarcity between blood meals, redox imbalance, and osmotic stresses induced by the triatomine's metabolism. To endure these conditions, &lt;i&gt;T. cruzi&lt;/i&gt; has developed a remarkably versatile metabolic network enabling it to metabolize sugars, lipids, and amino acids efficiently. However, the full extent of metabolites this parasite can thrive on remains incompletely understood. This study reveals that, beyond conventional carbon and energy sources (glucose, palmitic acids, proline, histidine, glutamine, and alanine), three additional metabolites (serine, threonine, and glycine) play vital roles in the parasite's survival during starvation. Remarkably, serine and threonine directly contribute to ATP production through a serine/threonine ","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0098324"},"PeriodicalIF":3.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557464","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":"Cross-laboratory replication of pseudomyxoma peritonei tumor microbiome reveals reproducible microbial signatures.","authors":"Victoria F Nieciecki, Faith C Blum, Ryan C Johnson, Traci L Testerman, Tom J McAvoy, Mary Caitlin King, Vadim Gushchin, Jeannette M Whitmire, Kenneth G Frey, Lindsay Glang, Dessiree Peña-Gomez, Kimberly A Bishop-Lilly, Armando Sardi, D Scott Merrell, Jessica L Metcalf","doi":"10.1128/msphere.00652-24","DOIUrl":"10.1128/msphere.00652-24","url":null,"abstract":"<p><p>Recent work has demonstrated that cancer-specific microbial communities often colonize tumor tissues. However, untangling low-biomass signals from environmental contamination makes this research technically challenging. We utilize pseudomyxoma peritonei (PMP), a cancer characterized by the spread of mucus-secreting cells throughout the peritoneal cavity, to develop a robust workflow for identifying reproducible tumor microbiomes. Typically originating from the rupture of an appendiceal tumor into the peritoneal cavity, metastasized tumors have been previously shown to harbor a core set of microbes. However, that work did not control for the potential contamination of these low microbial biomass samples. We expand upon these prior findings by characterizing the microbiome of 70 additional PMP tumors and six normal peritoneal control tissues along with appropriate laboratory controls. Additionally, DNA from a subset of 25 tissues was extracted and sequenced at an independent laboratory. We found evidence of reproducible microbial signatures between the replicates of six different PMP tumors that include a set of core taxa that may be introduced from surgical contamination, as well as patient-specific taxa that are also commonly implicated in colorectal cancer. In addition, preoperative chemotherapy treatment was found to reduce tumor microbiome diversity. Our findings demonstrate how independent sample replication can be a powerful approach to investigate low-biomass microbial communities associated with tumor tissues that will improve low microbial biomass research.IMPORTANCERecent work has demonstrated that microbial communities colonize over 30 different types of tumor tissues. The origin of these communities and their possible involvement in carcinogenesis or cancer treatment outcomes remains an unclear, yet important area of research. A current major challenge in characterizing low-biomass, tumor-associated microbiomes is the introduction of environmental contamination during collection, handling, DNA extraction, PCR, and sequencing. Here, we provide a framework for replicating low-biomass tumor microbiome samples to help identify tumors with robust microbial signals and low background contamination. Using this replication approach, we show that pseudomyxoma peritonei (PMP) tumors host reproducible microbial communities, including organisms that have previously been associated with colorectal cancer. Incorporating sample replication into future tumor microbiome studies is a promising approach that will help identify robust signals and increase reproducibility in the field.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0065224"},"PeriodicalIF":3.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458622","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":"<i>Toxoplasma gondii</i> PROP1 is critical for autophagy and parasite viability during chronic infection.","authors":"Pariyamon Thaprawat, Fengrong Wang, Shreya Chalasani, Tracey L Schultz, Manlio Di Cristina, Vern B Carruthers","doi":"10.1128/msphere.00829-24","DOIUrl":"10.1128/msphere.00829-24","url":null,"abstract":"<p><p>Macroautophagy is an important cellular process involving lysosomal degradation of cytoplasmic components, facilitated by autophagy-related proteins. In the protozoan parasite <i>Toxoplasma gondii</i>, autophagy has been demonstrated to play a key role in adapting to stress and the persistence of chronic infection. Despite limited knowledge about the core autophagy machinery in <i>T. gondii</i>, two PROPPIN family proteins (TgPROP1 and TgPROP2) have been identified with homology to Atg18/WIPI. Prior research in acute-stage tachyzoites suggests that TgPROP2 is predominantly involved in a non-autophagic function, specifically apicoplast biogenesis, while TgPROP1 may be involved in canonical autophagy. Here, we investigated the distinct roles of TgPROP1 and TgPROP2 in chronic stage <i>T. gondii</i> bradyzoites, revealing a critical role for TgPROP1, but not TgPROP2, in bradyzoite autophagy. Conditional knockdown of TgPROP2 did not impair bradyzoite autophagy. In contrast, TgPROP1 KO parasites had impaired autolysosome formation, reduced cyst burdens in chronically infected mice, and decreased viability. Together, our findings clarify the indispensable role of TgPROP1 to <i>T. gondii</i> autophagy and chronic infection.</p><p><strong>Importance: </strong>It is estimated that up to a third of the human population is chronically infected with <i>Toxoplasma gondii</i>; however, little is known about how this parasite persists long term within its hosts. Autophagy is a self-eating pathway that has recently been shown to play a key role in parasite persistence, yet few proteins that carry out this process during <i>T. gondii</i> chronic infection are known. Here, we provide evidence for a non-redundant role of TgPROP1, a protein important in the early steps of the autophagy pathway. Genetic disruption of TgPROP1 resulted in impaired autophagy and chronic infection of mice. Our results reveal a critical role for TgPROP1 in autophagy and underscore the importance of this pathway in parasite persistence.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0082924"},"PeriodicalIF":3.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468574","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 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}

{"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}