mSphere最新文献

{"title":"Discovery of sporogeny in the malaria transmission-blocking symbiont of <i>Anopheles</i> mosquitoes.","authors":"Jeremy K Herren","doi":"10.1128/msphere.00325-25","DOIUrl":"https://doi.org/10.1128/msphere.00325-25","url":null,"abstract":"<p><p>In recent work, Parry et al. provide a detailed visualization of <i>Microsporidia</i> MB sporogeny (E. R. S. Parry, R. Pevsner, B. C. Poulton, D.-K. Purusothaman, et al., mSphere 10:e00851-24, 2025, https://doi.org/10.1128/msphere.00851-24). Their findings reveal that <i>Microsporidia</i> MB is localized to mosquito germline tissues and undergoes octosporogony within developing oocytes, suggesting both vertical and potential horizontal transmission routes. The identification of spores with hallmark microsporidian structures strengthens the case for environmental dissemination via egg deposition. These results fill key biological knowledge gaps and set new methodological standards for <i>in vivo</i> symbiont imaging. This work advances <i>Microsporidia</i> MB's feasibility as a transmission-blocking symbiont and supports its development as a novel, sustainable malaria control tool.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0032525"},"PeriodicalIF":3.1,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855866","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":"Fibroblasts enhance the growth and survival of adult feline small intestinal organoids.","authors":"Nicole D Hryckowian, Katelyn Studener, Waneska S Frizzarini, David Arranz-Solís, Roberto Sánchez-Sánchez, Laura J Knoll","doi":"10.1128/msphere.00290-25","DOIUrl":"10.1128/msphere.00290-25","url":null,"abstract":"<p><p>Intestinal organoids are important cell culture models that complement live animal studies of many intestinal pathogens. Adult feline small intestinal organoids are needed for infectious disease research but are difficult to work with due to slow growth and premature senescence. We introduce a method of co-culturing adult feline small intestinal organoids with growth-inhibited human foreskin fibroblast feeder cells to enhance organoid proliferation and survival. With feeder cells, feline jejunal and ileal organoids survived at least 9 months in culture until cryopreservation. Fibroblast supplementation increased the maximum size of cat and mouse intestinal organoids as well. The increased longevity and size of these organoids are a significant improvement on current methods. These organoids also supported pre-sexual development of the medically important parasite <i>Toxoplasma gondii</i>, as evidenced by expression of the merozoite-specific marker GRA11b. This GRA11b positivity was higher in mature cat organoid-derived monolayers grown for 21 days prior to infection, compared with monolayers grown for 10 days. These methods have high potential to reduce the number of cats used for infectious disease research and may be applicable for intestinal cells from other animals that are difficult to culture.IMPORTANCEMany microbial pathogens are acquired orally through contaminated food or water. Being able to model these infections in cell culture has been greatly enhanced by the development of intestinal organoid technology. One of the species that hosts several infections is cats, but cat intestinal organoids have been notoriously difficult to grow. Here, we describe a co-culture method with fibroblast cells that dramatically improves the longevity of adult cat intestinal organoids. These cat organoid cells can support the pre-sexual development stages of the intestinal pathogen <i>Toxoplasma gondii</i>, a parasite whose sexual cycle is restricted to cats and is the reason that pregnant women are told not to change the litter box. These culture conditions will be a resource to study other cat intestinal pathogens and intestinal organoids from other animals that are difficult to culture.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0029025"},"PeriodicalIF":3.1,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799734","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":"The development of functional opsonophagocytic assays to evaluate antibody responses to <i>Klebsiella pneumoniae</i> capsular antigens.","authors":"Robert Lawrence, Emma Bownes, Marina Johnson, Heather Fox, Drew Huff, Ivan Olave, Anup Datta, David Goldblatt, Nathalie Karaky","doi":"10.1128/msphere.00176-25","DOIUrl":"10.1128/msphere.00176-25","url":null,"abstract":"<p><p><i>Klebsiella pneumoniae</i> is one of the leading causes of nosocomial infections in low- and middle-income countries (LMICs), with a high mortality rate among the immunocompromised. With increasing antibiotic resistance, there is an urgent need for preventive measures such as vaccines, but none are currently licensed for use. In order to evaluate natural immunity and assess the immunogenicity of novel vaccines, we set out to develop functional assays that effectively measure the immune response of <i>K. pneumoniae</i> anti-capsular antibodies <i>in vitro</i>. Serotypes KL2, KL15, KL25, KL62, and KL102 were targeted as these are five of the most prevalent and invasive strains, particularly in LMIC settings, and are putative vaccine antigens. Opsonophagocytic killing assays (OPAs) for each serotype were developed and qualified. Serotype-specific IgG from vaccinated rabbit sera and human sera was used to demonstrate <i>in vitro</i> antibody and complement-mediated killing for all serotypes tested, whereas cross-reactivity between each serotype was minimal by competitive analyses. These assays act as a platform to allow further serological evaluation of natural immunity and the performance of <i>K. pneumoniae</i> vaccines. Understanding the function of vaccine-induced antibodies, as well as natural IgG induced by exposure to <i>K. pneumoniae</i>, will be crucial to determine correlates of protection and aid in the path to licensure of a <i>K. pneumoniae</i> vaccine.IMPORTANCE<i>K. pneumoniae</i> is a pathogen that causes serious infections such as pneumonia and sepsis globally. The increasing prevalence of antibiotic resistance in this pathogen has complicated treatment efforts, highlighting the need for preventive therapeutic strategies such as vaccination. However, no licensed vaccines are currently available. Standardized assays to assess the immunogenicity of new vaccines are crucial for vaccine development and evaluation of other therapeutics. Therefore, we have developed assays that can assess the functionality of antibodies, which can be used to evaluate the potential of novel <i>K. pneumoniae</i> conjugate vaccines, and inform which antibodies are most effective for preventing disease.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0017625"},"PeriodicalIF":3.1,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12306171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275405","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":"Dynamics of amylopectin granule accumulation during the course of chronic <i>Toxoplasma</i> infection is linked to intra-cyst bradyzoite replication.","authors":"Aashutosh Tripathi, Ryan W Donkin, Joy S Miracle, Robert D Murphy, Matthew S Gentry, Abhijit Patwardhan, Anthony P Sinai","doi":"10.1128/msphere.00205-25","DOIUrl":"10.1128/msphere.00205-25","url":null,"abstract":"<p><p>The contribution of amylopectin granules (AG), a branched chain storage homopolymer of glucose, to the maintenance and progression of the chronic <i>Toxoplasma gondii</i> infection has remained undefined. Here, we describe the role of AG in the physiology of encysted bradyzoites using a purpose-developed imaging-based application, AmyloQuant, which permitted the quantification of relative levels of AG within <i>in vivo</i>-derived tissue cysts during the initiation and maturation of chronic infection. Our findings establish that AG are dynamic, exhibiting considerable heterogeneity among tissue cysts at all post-infection time points examined. Quantification of relative steady-state AG levels within tissue cysts reveals a previously unrecognized temporal cycle involving both phases of AG accumulation and utilization over the first 6 weeks of the chronic infection. This AG cycle is temporally coordinated with overall bradyzoite mitochondrial activity. In addition, the staging of AG levels is defined by a period of low accumulation, leading into a phase of high accumulation, followed by apparent rapid utilization associated with a coordinated burst of intra-cyst bradyzoite replication. These findings suggest that AG may represent a key component in the licensing of bradyzoite replication, intimately linking stored metabolic potential to the course of the chronic infection, thereby extending the impact of AG beyond the previously assigned role in transmission. These findings force a fundamental reassessment of the chronic <i>Toxoplasma</i> infection, highlighting the critical need to address the temporal progression of this crucial stage in the parasite life cycle.IMPORTANCEAmylopectin granules (AG) represent a storage polymer of glucose within <i>Toxoplasma gondii</i> bradyzoites, the life cycle stage associated with the chronic infection. In this study, we report on the development of AmyloQuant, an image-based application, to investigate the levels and distribution of AG within encysted bradyzoites in the murine brain with the progression of the chronic infection. Quantification reveals that AG, although heterogeneous both within and across tissue cysts, exhibit a previously unrecognized temporal cycle that is linked to the overall mitochondrial activity and the capacity to replicate <i>in vivo</i>. This confirms that encysted bradyzoites, long considered dormant, retain considerable metabolic activity, with AG playing a potentially critical role in defining and perhaps licensing the progression of this life-long persistent infection.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0020525"},"PeriodicalIF":3.1,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12306163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258521","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 <i>Plasmodium falciparum</i> homolog of Vps16 interacts with the core members of the Vps-C tethering complex.","authors":"Florian Lauruol, Thomas Galaup, Alexandra Bourgeois, Audrey Sergerie, Dave Richard","doi":"10.1128/msphere.00287-25","DOIUrl":"10.1128/msphere.00287-25","url":null,"abstract":"<p><p>The organelles of the apical complex (rhoptries, micronemes, and dense granules) are critical for erythrocyte invasion by the malaria parasite <i>Plasmodium falciparum</i>. Though they have essential roles in the parasite lifecycle, the mechanisms behind their biogenesis are still poorly defined. The Class C Vps proteins Vps11, Vps16, Vps18, and Vps33 constitute the core of the CORVET and HOPS complexes implicated in vesicle tethering and fusion in the eukaryotic endolysosomal system. Work in the model apicomplexan <i>Toxoplasma gondii</i> has revealed that TgVps11 is essential for the generation of the apical complex. <i>P. falciparum</i> possesses all four subunits of the Vps-C complex, and recent work has shown that some of its components were critical for host-cell cytosol trafficking and the biogenesis of the apical complex. We here show that the <i>P. falciparum</i> ortholog of Vps16, a member of the Vps-C complex, is expressed throughout the asexual erythrocytic cycle and that it is potentially associated with the Golgi apparatus and the rhoptries in schizont stage parasites. We then demonstrate by immunoprecipitation and mass spectrometry that PfVps16 interacts with all the members of the canonical Vps-C complex along with the Vps3 CORVET component. Interestingly, three uncharacterized <i>Plasmodium</i>-specific proteins are also found as interactors of PfVps16, and structural predictions revealed that two of them possess folds commonly found in proteins present in membrane tethering complexes. These findings suggest that <i>P. falciparum</i> may possess both conserved and parasite-specific features within its endosomal tethering machinery.IMPORTANCEThe malaria parasite relies on special compartments to invade red blood cells. These are key to the parasite's ability to infect, but how these are generated is not well known. In eukaryotic cells, certain protein assemblies, called tethering complexes, help move and fuse small transport vesicles, which is important for building and maintaining organelles. <i>Plasmodium falciparum</i> possesses some of these proteins, and recent studies suggest they play an important role in building its infection machinery and transporting material inside the parasite. We found that the malaria parasite possesses additional components associated with the typical tethering proteins and that these are not found in other eukaryotes. These results suggest that <i>P. falciparum</i> uses both common and unique tools to create the cellular machinery it needs to infect red blood cells. We propose that the <i>Plasmodium</i>-specific components might represent interesting targets for the development of antimalarials with potentially reduced side effects since they are not present in humans.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0028725"},"PeriodicalIF":3.1,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12306165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584375","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":"NLP-like deep learning aided in identification and validation of thiosulfinate tolerance clusters in diverse bacteria.","authors":"Brendon K Myers, Anuj Lamichhane, Brian H Kvitko, Bhabesh Dutta","doi":"10.1128/msphere.00023-25","DOIUrl":"10.1128/msphere.00023-25","url":null,"abstract":"<p><p>Allicin tolerance (<i>alt</i>) clusters in phytopathogenic bacteria, which provide resistance to thiosulfinates like allicin, are challenging to find using conventional approaches due to their varied architecture and the paradox of being vertically maintained within genera despite likely being horizontally transferred. This results in significant sequential diversity that further complicates their identification. Natural language processing (NLP), like techniques such as those used in DeepBGC, offers a promising solution by treating gene clusters like a language, allowing for identifying and collecting gene clusters based on patterns and relationships within the sequences. We curated and validated <i>alt</i>-like clusters in <i>Pantoea ananatis</i> 97-1R, <i>Burkholderia gladioli</i> pv. <i>gladioli</i> FDAARGOS 389, and <i>Pseudomonas syringae</i> pv. tomato DC3000. Leveraging sequences from the RefSeq bacterial database, we conducted comparative analyses of gene synteny, gene/protein sequences, protein structures, and predicted protein interactions. This approach enabled the discovery of several novel <i>alt</i>-like clusters previously undetectable by other methods, which were further validated experimentally. Our work highlights the effectiveness of NLP-like techniques for identifying underrepresented gene clusters and expands our understanding of the diversity and utility of <i>alt</i>-like clusters in diverse bacterial genera. This work demonstrates the potential of these techniques to simplify the identification process and enhance the applicability of biological data in real-world scenarios.IMPORTANCEThiosulfinates, like allicin, are potent antifeedants and antimicrobials produced by <i>Allium</i> species and pose a challenge for phytopathogenic bacteria. Phytopathogenic bacteria have been shown to utilize an allicin tolerance (<i>alt</i>) gene cluster to circumvent this host response, leading to economically significant yield losses. Due to the complexity of mining these clusters, we applied techniques akin to natural language processing to analyze Pfam domains and gene proximity. This approach led to the identification of novel <i>alt</i>-like gene clusters, showcasing the potential of artificial intelligence to reveal elusive and underrepresented genetic clusters and enhance our understanding of their diversity and role across various bacterial genera.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0002325"},"PeriodicalIF":3.1,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12306174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317517","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 ionophore resistance genes <i>narA</i> and <i>narB</i> are geographically widespread and linked to resistance to medically important antibiotics.","authors":"Asalia Ibrahim, Jason Au, Alex Wong","doi":"10.1128/msphere.00243-25","DOIUrl":"10.1128/msphere.00243-25","url":null,"abstract":"<p><p>Ionophores are a class of antibiotics used widely in animal production as anti-coccidials and for growth promotion. Since ionophores are not used in human medicine, it has largely been assumed that they do not contribute to medically important antimicrobial resistance (AMR). Nonetheless, there is increasing concern that ionophore usage could co-select for clinically relevant AMR, since the ionophore resistance genes <i>narA</i> and <i>narB</i> have been found in linkage with multiple AMR genes. We investigated the global distribution and AMR linkage of <i>narA</i> and <i>narB</i> using publicly available data. These ionophore resistance genes can be found worldwide, with >2,400 <i>narAB</i>-bearing isolates reported from 51 countries. Isolates were derived from a range of host species, including poultry, cattle, and humans. <i>narAB</i> was linked with an average of over 10 resistance determinants for AMR, including many medically important antibiotics. These observations indicate that we cannot assume that ionophore use is risk-free, with clear potential for co-selection for clinically relevant AMR.IMPORTANCEIonophores are a type of antibiotic used to promote growth in cattle and pigs and to treat parasitic infections in poultry. It has been assumed that ionophore use in animals does not pose a risk for humans. However, growing evidence suggests that ionophore use may select for medically relevant antibiotic resistance. Using analyses of public data, we found that ionophore resistance is widespread and that it is usually linked to resistance genes for medically relevant drugs. There is thus clear potential for ionophore use to impact the presence of antibiotic resistance genes in the food supply.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0024325"},"PeriodicalIF":3.1,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12306154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317518","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":"Human papillomavirus 16 mitigates <i>Sneathia vaginalis</i>-induced damage to cervical keratinocytes.","authors":"Phoebe V Bridy, Jasmine C Cruz, Jada L Covington, Taharah I Islam, Catherine E Hadley, Kayla Tran, Rachel Fry, Bradley A Sheffield, Myrna Serrano, Gregory A Buck, Jinlei Zhao, Katherine Y Tossas, Craig Meyers, Iain M Morgan, Claire D James, Kimberly K Jefferson","doi":"10.1128/msphere.00152-25","DOIUrl":"10.1128/msphere.00152-25","url":null,"abstract":"<p><p><i>Sneathia vaginalis</i> is a bacterial component of the vaginal microbiome that is of clinical interest because of its association with preterm birth and other obstetric complications. It produces a cytotoxin, but little is known about the mechanism through which it kills epithelial cells or the role that cytotoxicity plays in bacterial survival. Recent microbiome studies demonstrate an association between <i>S. vaginalis</i> and human papillomavirus (HPV) within the female reproductive tract, suggesting that HPV and <i>S. vaginalis</i> could interact in some way within this shared niche. We analyzed 16S rRNA survey and HPV typing data from our Vaginal Human Microbiome Project and found, in agreement with other reports, that <i>S. vaginalis</i> was associated with HPV infection. To test the hypothesis that HPV promotes the growth of <i>S. vaginalis</i>, growth and cytotoxicity of <i>S. vaginalis</i> in co-culture with HPV16-positive and HPV-negative human cervical keratinocytes (HCK) were quantitatively assessed. Organotypic HCK rafts expressing HPV16 were more resistant to <i>S. vaginalis</i>-induced damage, as assessed by histology, and supported increased bacterial growth relative to HPV-negative HCK rafts. When <i>S. vaginalis</i> was co-cultured with HPV16-positive and HPV-negative HCK monolayers, cytotoxicity was observed in both HPV16-positive and HPV-negative cells, but HPV16-positive cells were more resistant to the toxic effects of the bacteria and supported bacterial growth for an extended period of time. In conclusion, HPV16 may protect cervical keratinocytes from the cytotoxic effects of <i>S. vaginalis</i>, preventing the eradication of colonized cells and supporting bacterial growth, and this could underlie the association between <i>S. vaginalis</i> and HPV <i>in vivo</i>.IMPORTANCE<i>Sneathia vaginalis</i> (<i>S. vaginalis</i>) is a bacterial species that lives in the human vagina and can cause complications during pregnancy if it invades the uterus. It is capable of killing cervical epithelial cells. Human papillomaviruses (HPV) are sexually transmitted viruses that can cause genital lesions and cervical cancer. Recently, multiple reports describe an association between <i>S. vaginalis</i> and HPV. This study used cultured cervical epithelial cells expressing the high-risk HPV type, HPV16, and HPV-negative cells to determine whether HPV promotes the growth of <i>S. vaginalis</i>. We found that HPV16 promotes the survival of cervical epithelial cells that are exposed to <i>S. vaginalis</i>. Survival of cervical epithelial cells may benefit the growth of <i>S. vaginalis</i>, which adhere to and feed off of these cells to survive in the female reproductive tract.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0015225"},"PeriodicalIF":3.1,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12306162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540968","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":"Straining to define a healthy microbiome.","authors":"Anna M Seekatz","doi":"10.1128/msphere.00797-24","DOIUrl":"10.1128/msphere.00797-24","url":null,"abstract":"<p><p>In 2020, I wrote an mSphere of Influence commentary on two studies that shaped my research perspective on the human gut microbiome (McNulty et al., Sci Transl Med 3:106ra106, 2011, https://doi.org/10.1126/scitranslmed.3002701; Hamilton et al., Gut Microbes 4:125, 2013, https://doi.org/10.4161/gmic.23571). The microbiome field has continued to progress since the publication of these studies over 10 years ago, emerging as a considerable factor in almost all areas focused on disease development. My previous commentary highlighted two areas that piqued my interest early on in my career: (i) that the extant microbial community should be considered when proposing to manipulate the microbiota, such as via probiotics or fecal microbiota transplantation, and (ii) that realized (i.e., transcribed) functional changes of the microbiota may occur independent of changes in its composition. Since writing that commentary, two microbiota-based therapeutics for the treatment of <i>Clostridioides difficile</i> infection have been approved, highlighting the potential success of using the microbiota to treat or prevent disease. Despite these wins and ever-growing evidence of the importance of the microbiome in managing our health, translating mechanistic studies into therapeutic value has been slower. In this minireview, I expand upon two large questions that would increase our ability to translate the microbiome into therapies, highlighting both historical and recent progress.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0079724"},"PeriodicalIF":3.1,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12306167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608908","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":"Dental biofilm serves as an ecological reservoir of acidogenic pathobionts in head and neck cancer patients with radiotherapy-related caries.","authors":"Julia S Bruno, Vitor Heidrich, Felipe C F Restini, Tatiana M M T Alves, Wanessa Miranda-Silva, Franciele H Knebel, Elisangela M Cóser, Lilian T Inoue, Paula F Asprino, Anamaria A Camargo, Eduardo R Fregnani","doi":"10.1128/msphere.00257-25","DOIUrl":"10.1128/msphere.00257-25","url":null,"abstract":"<p><p>Radiotherapy-related caries (RRC) is an aggressive and debilitating oral toxicity that affects half of the patients who undergo radiotherapy for head and neck cancer. However, the etiology of RRC is not fully established, and there are no clinically validated methods for preventing it. To gain a better understanding of the risk factors and the microbiome's role in causing RRC, we compared clinicopathological characteristics, oncological treatment regimens, oral health condition, and the oral microbiota at three different oral sites of radiotherapy-treated patients with (RRC+) and without radiotherapy-related caries (RRC-). We observed no significant differences between these groups in the clinicopathological characteristics and treatment regimens. However, RRC+ patients were older and had poorer oral health conditions at the start of the radiotherapy treatment, with a lower number of teeth and a higher proportion of rehabilitated teeth. RRC+ patients had lower microbiota diversity and the dental biofilm of RRC+ patients displayed striking alterations in microbiome composition compared to RRC- patients, including enrichment of acidogenic species and altered metabolic potential, with a higher abundance of genes linked to energy-related pathways associated with the synthesis of amino acids and sugars. We also compared the microbiota of RRC+ tissue with conventional caries tissue, revealing lower bacterial diversity and enrichment of Lactobacillaceae members in RRC+. The insights into the irradiated oral microbiota enhance the understanding of RRC etiology and highlight the potential for microbial-targeted therapies in its prevention and treatment.</p><p><strong>Importance: </strong>This study focuses on a dedicated collection of diverse oral sites to comprehensively investigate microbial differences between patients who develop RRC and those who do not. RRC is a severe oral disease that profoundly impacts on the oral health and overall quality of life of cancer survivors. Leveraging shotgun metagenomics, we characterize the unique microbial variations in <i>in vivo</i> irradiated dental biofilms, unveiling novel insights into the microbial ecology of radiotherapy-treated patients. Furthermore, this research integrates extensive data on oral health and oncological profiles, providing a comprehensive understanding of the intricate relationship between oral microbial communities and the outcomes of radiotherapy-induced toxicity.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0025725"},"PeriodicalIF":3.1,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12306161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528956","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}