mSpherePub Date : 2025-06-25Epub Date: 2025-06-06DOI: 10.1128/msphere.00211-25
Carlos J Ramírez-Flores
{"title":"mSphere of Influence: Adapting new models for studying <i>Toxoplasma gondii</i> gut interactions.","authors":"Carlos J Ramírez-Flores","doi":"10.1128/msphere.00211-25","DOIUrl":"10.1128/msphere.00211-25","url":null,"abstract":"<p><p>Carlos J. Ramírez-Flores works in the field of parasitology, focusing on how <i>Toxoplasma gondii</i> crosses host barriers. In this mSphere of Influence article, he reflects on how three papers-by Shim, Kim, and Gregg-built on Dubey's foundational mouse work to reshape his view of the parasite's earliest intestinal events and to inspire his use of gut-on-chip platforms.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0021125"},"PeriodicalIF":3.7,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234611","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 : 2025-06-25Epub Date: 2025-05-16DOI: 10.1128/msphere.00189-25
Kevin Munoz Navarrete, Kathryn M Edwards, Kingston H G Mills, Jana Kamanová, María Eugenia Rodriguez, Andrew Gorringe, Andrew Preston, Beate Kampmann, Monica C Gestal, Eric T Harvill, Purnima Dubey, Dimitri A Diavatopoulos, Seema Mattoo, Karen M Scanlon, Camille Locht, Peter Sebo
{"title":"Highlights of the 14th International <i>Bordetella</i> Symposium.","authors":"Kevin Munoz Navarrete, Kathryn M Edwards, Kingston H G Mills, Jana Kamanová, María Eugenia Rodriguez, Andrew Gorringe, Andrew Preston, Beate Kampmann, Monica C Gestal, Eric T Harvill, Purnima Dubey, Dimitri A Diavatopoulos, Seema Mattoo, Karen M Scanlon, Camille Locht, Peter Sebo","doi":"10.1128/msphere.00189-25","DOIUrl":"10.1128/msphere.00189-25","url":null,"abstract":"<p><p>Pertussis, or whooping cough, is a highly contagious and acute respiratory illness caused primarily by the gram-negative coccobacillus <i>Bordetella pertussis</i>. Despite near-universal vaccination, pertussis remains one of the least-controlled vaccine-preventable infectious diseases. Since 2023, pertussis incidence has been rising, and widespread pertussis outbreaks have resurged in many countries. In response to these emerging challenges, almost 300 experts from institutions across 24 countries convened at the 14th International <i>Bordetella</i> Symposium in Prague, Czech Republic, from 24 to 28 June 2024 to discuss pertussis epidemiology and research and strategies to mitigate the global pertussis burden. We present here the highlights of the symposium, comprising epidemiological and clinical aspects of <i>Bordetella</i> infections, results of clinical trials of pertussis vaccination in pregnant women and effectiveness of maternal vaccination in protecting newborn infants in Africa and Europe, the controlled human infection model (CHIM), and the latest insights into the biology, immunology, and pathogenesis of <i>B. pertussis</i> infection.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0018925"},"PeriodicalIF":3.7,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079234","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 : 2025-06-25Epub Date: 2025-05-16DOI: 10.1128/msphere.00190-25
Daniel F Q Smith, Aviv Bergman, Arturo Casadevall
{"title":"The dynamics of <i>Cryptococcus neoformans</i> infection in <i>Galleria mellonella</i>.","authors":"Daniel F Q Smith, Aviv Bergman, Arturo Casadevall","doi":"10.1128/msphere.00190-25","DOIUrl":"10.1128/msphere.00190-25","url":null,"abstract":"<p><p><i>Galleria mellonella</i> has emerged as an important host for the study of fungal virulence, insect immune responses, and the evaluation of antifungal agents. In this study, we investigated the dynamics of fungal infections in <i>G. mellonella</i> using <i>Cryptococcus neoformans</i>, a human pathogenic fungus. Since the analysis of infection dynamics requires a fine temporal resolution of larval death, we employed a photographic time-lapse technique that allowed us to simultaneously measure death by proxy of larval melanization and absence of movement. Larval mortality occurred in two phases, early and late, which differed in their timing of melanization. Early phase deaths occurred with rapid whole-body onset of melanization, followed by sudden cessation of movement several hours later. Contrastingly, late phase deaths occurred with a gradual cessation of movement, followed by melanization, typically radiating from one location on the larva. The differences in mortality kinetics suggest differences in fungal pathogenesis, with one population succumbing early while the rest linger for later death. Subsequent analysis of mortality data using the inversion method revealed predictable deterministic dynamics but did not observe evidence of chaotic signatures. While this does not preclude the existence of chaos, it indicates that this <i>C. neoformans-G. mellonella</i> infection model may behave differently than bacterial-insect models.IMPORTANCEThe ability to predict the course of an infection is critical in anticipating disease progression and effectively treating patients. Similarly, the ability to make predictions about pathogenesis in laboratory infection models could further our understanding of pathogenesis and lead to new treatments. As fungal diseases are expected to rise, understanding the dynamics of fungal infections will be important to anticipate and mitigate future threats. Here, we developed a time-lapse method to visualize infections of <i>Galleria mellonella</i> larvae with the fungal pathogen <i>Cryptococcus neoformans</i>. This method provided insight into infection progression that is not apparent from standard survival measurement protocols, including the relationship between melanization and death. Further, it enabled us to explore the dynamics of disease progression in this system, which revealed deterministic dynamics without evidence of chaos, implying predictability in the outcome of cryptococcal infection in this moth.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0019025"},"PeriodicalIF":3.7,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079236","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":"Alterations of fecal microbiota and plasma metabolome in patients with Parkinson's disease with rapid eye movement sleep disorder.","authors":"Yangdanyu Li, Yuning Liu, Fujia Li, Xu Liu, Zixuan Zhang, Jinyu Li, Guiyun Cui, Chuanying Xu","doi":"10.1128/msphere.00590-24","DOIUrl":"10.1128/msphere.00590-24","url":null,"abstract":"<p><p>Patients with Parkinson's disease (PD) with probable rapid eye movement sleep behavior disorder (RBD) (PD-RBD), a specific subtype of PD, are characterized by the presence of more severe motor and non-motor symptoms. This study aimed to elucidate the characteristics and interactions of gut microbiota and plasma metabolic characteristics of PD-RBD, thus screening for the disease mechanisms. A total of 100 PD patients, 50 healthy controls (HCs) and 16 probable idiopathic RBD (iRBD) patients were collected. There were 33 PD-RBD and 67 patients without probable RBD (PD-nRBD) in PD patients. DNA extraction, PCR amplification, and high-throughput sequencing were used for intestinal microbiota analysis, and ultra-high liquid chromatography tandem mass spectrometry was used for metabolome analysis. Spearman analysis was applied to investigate the correlation of fecal microbiota and plasma metabolome. Our findings revealed <i>Lactobacillacea</i>e (<i>P</i> = 0.017), <i>Christensenellaceae</i> (<i>P</i> = 0.017), <i>Fusobacteriaceae</i> (<i>P</i> = 0.018), <i>Lactobacillus</i> (<i>P</i> = 0.035), <i>Christensenellaceae</i> R-7 group (<i>P</i> = 0.035), and <i>Fusobacterium</i> (<i>P</i> = 0.035) were significantly different in PD-RBD, PD-nRBD, and HC. Moreover, the differential metabolites identified in both PD-nRBD and PD-RBD were 3-hydroxy-2-methylpyridine-4,5-dicarboxylate (VIP = 5.802) and 3-methoxy-4-hydroxyphenylglycol sulfate (VIP = 5.732). Furthermore, our analysis revealed that 3-methoxy-4-hydroxyphenylglycol sulfate showed a positive correlation with <i>Lactobacillus</i> (<i>r</i> = 0.197, <i>P</i> = 0.049). Finally, functional analysis indicated that these distinctive microbiota and metabolites were primarily associated with phenylalanine metabolism and vitamin B6 metabolism. We managed to show that the differential microbiota, differential metabolites, and their interactions in PD-RBD compared to PD-nRBD and HC. This furthers our understanding of disease pathogenesis, and offers fresh perspectives on its detection and treatment.</p><p><strong>Importance: </strong>There are currently fewer investigations on the intestinal microbiota and metabolites of probable rapid eye movement sleep behavior disorder (PD-RBD) and idiopathic RBD (iRBD). Our findings indicate that PD-RBD exhibits an increase in <i>Christensenellaceae</i> and 3-methoxy-4-hydroxyphenethyleneglycol sulfate, and that iRBD exhibits a similar trend. This suggests that the PD prodromal stage may have seen this alteration. Furthermore, functional analysis indicated that these distinctive microbiota and metabolites were primarily associated with phenylalanine metabolism and vitamin B6 metabolism. Basic experiments and multi-center, large-cohort clinical researches are worth conducting to confirm this, since they may offer insights for treating individuals with PD-RBD.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0059024"},"PeriodicalIF":3.7,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002624","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 : 2025-06-25Epub Date: 2025-05-14DOI: 10.1128/msphere.00240-25
Michael J Imperiale, Arturo Casadevall
{"title":"Two golden anniversaries in the biological sciences.","authors":"Michael J Imperiale, Arturo Casadevall","doi":"10.1128/msphere.00240-25","DOIUrl":"10.1128/msphere.00240-25","url":null,"abstract":"","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0024025"},"PeriodicalIF":3.7,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035944","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 : 2025-06-25Epub Date: 2025-05-22DOI: 10.1128/msphere.00021-25
Tamiru N Alkie, Carissa Embury-Hyatt, Anthony V Signore, Frank Baldwin, Tamiko Hisanaga, Wanhong Xu, Estella Moffat, Jolene A Giacinti, Catherine Soos, Yohannes Berhane
{"title":"Comparative pathogenicity of three A(H5N1) clade 2.3.4.4b HPAI viruses in blue-winged teal and transmission to domestic poultry.","authors":"Tamiru N Alkie, Carissa Embury-Hyatt, Anthony V Signore, Frank Baldwin, Tamiko Hisanaga, Wanhong Xu, Estella Moffat, Jolene A Giacinti, Catherine Soos, Yohannes Berhane","doi":"10.1128/msphere.00021-25","DOIUrl":"10.1128/msphere.00021-25","url":null,"abstract":"<p><p>Long-distance migratory ducks play a critical role in the maintenance and dissemination of A(H5N1) viruses. Comparative pathogenicity studies were conducted on blue-winged teal (BWTE; <i>Anas discors</i>) using three distinct genotypes of A(H5N1) clade 2.3.4.4b viruses (A1, B1.3, and B4.1) isolated from wild ducks in Canada. Twenty-four hours post-intranasal infection of BWTE, contact turkeys and chickens were introduced into each of the groups to evaluate viral transmission. The levels of viral shedding in BWTE increased from 3 to 7 days post-infection (dpi) and continued at lower levels until 14 dpi. The A1 genotype virus (MALL/NS/22) was found to be the least pathogenic to BWTE compared to the reassortant genotypes, B4.1 (RBME/BC/22) and B1.3 (BWTE/MB/22). The B1.3 genotype was the most virulent to BWTE and caused 66.7% mortality compared to 12.5% mortality caused by the B4.1 genotype. The extent of transmission from infected BWTE to contact turkeys and chickens showed variations. Turkeys housed with BWTE infected with either virus died within 6 to 10 days post-contact (dpc). Conversely, the transmission and mortality among contact chickens varied. The highest mortality (3 out of 5) occurred in chickens exposed to BWTE infected with the B1.3 genotype. Whilst in the B4.1 genotype, 2 out of 6 chickens died, none of the chickens in the A1 genotype succumbed to infection. No shedding or seroconversion was noted in all surviving chickens. This research underscores variations in the pathogenic traits and transmissibility among the different genotypes of A(H5N1) clade 2.3.4.4b viruses. This finding is vital for understanding the role of migratory birds in the epidemiology of A(H5N1) and the need for continuous monitoring of these viruses.</p><p><strong>Importance: </strong>The recurrent incursions of A(H5N1) clade 2.3.4.4b viruses into North America have resulted in the emergence of reassortant virus genotypes. These genotypes exhibit variations in pathogenicity and host ranges. Blue-winged teal (BWTE) are the most common dabbling ducks in North America and play a crucial role in maintaining and dispersing influenza A viruses (IAVs). In some areas, the migratory pathways of BWTE overlap with densely populated commercial poultry facilities. Despite this, the role of BWTE in the maintenance and spread of A(H5N1) is not well understood, and there is limited data on their susceptibility to A(H5N1) clade 2.3.4.4b viruses. Our study demonstrates differences in BWTE susceptibility to distinct genotypes of A(H5N1) clade 2.3.4.4b viruses. The virus transmission from infected BWTE and lethality in turkeys and chickens were also influenced by the virus genotypes. The findings suggest that BWTE could contribute to the maintenance and spread of highly pathogenic avian influenza (HPAI) viruses, and active surveillance in BWTE is essential.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0002125"},"PeriodicalIF":3.7,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120358","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 : 2025-06-25Epub Date: 2025-06-03DOI: 10.1128/msphere.00114-25
Marcos Parras-Moltó, David Lund, Stefan Ebmeyer, D G Joakim Larsson, Anna Johnning, Erik Kristiansson
{"title":"The transfer of antibiotic resistance genes between evolutionarily distant bacteria.","authors":"Marcos Parras-Moltó, David Lund, Stefan Ebmeyer, D G Joakim Larsson, Anna Johnning, Erik Kristiansson","doi":"10.1128/msphere.00114-25","DOIUrl":"10.1128/msphere.00114-25","url":null,"abstract":"<p><p>Infections from antibiotic-resistant bacteria threaten human health globally. Resistance is often caused by mobile antibiotic resistance genes (ARGs) shared horizontally between bacterial genomes. Many ARGs originate from environmental and commensal bacteria and are transferred between divergent bacterial hosts before they reach pathogens. This process remains, however, poorly understood, which complicates the development of countermeasures that reduce the spread of ARGs. In this study, we aimed to systematically analyze the ARGs transferred between the most evolutionarily distant bacteria, defined here based on their phylum. We implemented an algorithm that identified inter-phylum transfers (IPTs) by combining ARG-specific phylogenetic trees with the taxonomy of the bacterial hosts. From the analysis of almost 1 million ARGs identified in >400,000 bacterial genomes, we identified 661 IPTs, which included transfers between all major bacterial phyla. The frequency of IPTs varies substantially between ARG classes and was highest for the aminoglycoside resistance gene AAC(3), while the levels for beta-lactamases were generally lower. ARGs involved in IPTs also differed between phyla, where, for example, tetracycline ARGs were commonly transferred between Firmicutes and Proteobacteria, but rarely between Actinobacteria and Proteobacteria. The results, furthermore, show that conjugative systems are seldom shared between bacterial phyla, suggesting that other mechanisms drive the dissemination of ARGs between divergent hosts. We also show that bacterial genomes involved in IPTs of ARGs are either over- or underrepresented in specific environments. These IPTs were also found to be more recent compared to transfers associated with bacteria isolated from water, soil, and sediment. While macrolide and tetracycline ARGs involved in IPTs almost always were >95% identical between phyla, corresponding β-lactamases showed a median identity of <60%. We conclude that inter-phylum transfer is recurrent, and our results offer new insights into how ARGs are disseminated between evolutionarily distant bacteria.</p><p><strong>Importance: </strong>Antibiotic-resistant infections pose a growing threat to global health. This study reveals how genes conferring antibiotic resistance can move between bacteria that belong to different phyla lineages previously thought to be too evolutionarily distant for frequent gene exchange. By analyzing nearly 1 million resistance genes from over 400,000 bacterial genomes, the researchers uncovered hundreds of inter-phylum transfer events, exposing surprising patterns in how different classes of resistance genes spread. The findings highlight that conjugative systems are less common than expected in cross-phyla transfers and suggest that alternative mechanisms may play key roles. This new understanding of how resistance genes leap between vastly different bacterial groups can inform strategies to slow the emergence of drug-resistan","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0011425"},"PeriodicalIF":3.7,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208941","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 : 2025-06-25Epub Date: 2025-05-14DOI: 10.1128/msphere.00137-25
Audra L Crouch, Beatrice M Severance, Susan Creary, Darryl Hood, Michael Bailey, Asuncion Mejias, Octavio Ramilo, Michelle Gillespie, Stefanie Ebelt, Vivien Sheehan, Benjamin T Kopp, Matthew Z Anderson
{"title":"Altered nasal and oral microbiomes define pediatric sickle cell disease.","authors":"Audra L Crouch, Beatrice M Severance, Susan Creary, Darryl Hood, Michael Bailey, Asuncion Mejias, Octavio Ramilo, Michelle Gillespie, Stefanie Ebelt, Vivien Sheehan, Benjamin T Kopp, Matthew Z Anderson","doi":"10.1128/msphere.00137-25","DOIUrl":"10.1128/msphere.00137-25","url":null,"abstract":"<p><p>Sickle cell disease (SCD) is a chronic blood disorder that disrupts multiple organ systems and can lead to severe morbidity. Persistent and acute symptoms caused by immune system dysregulation in individuals with SCD could contribute to disease either directly or indirectly via dysbiosis of commensal microbes and increased susceptibility to infection. Here, we explored the nasal and oral microbiomes of children with SCD (cwSCD) to uncover potential dysbiotic associations with the blood disorder. Microbiota collected from nasal and oral swabs of 40 cwSCD were compared to eight healthy siblings using shotgun metagenomic sequencing. Commensal taxa were present at similar levels in the nasal and oral microbiome of both groups. However, the nasal microbiomes of cwSCD contained a higher prevalence of Pseudomonadota species, including pathobionts such as <i>Yersinia enterocolitica</i> and <i>Klebsiella pneumoniae</i>. Furthermore, the oral microbiome of cwSCD displayed lower α-diversity and fewer commensal and pathobiont species compared to the healthy siblings. Thus, subtle but notable shifts seem to exist in the nasal and oral microbiomes of cwSCD, suggesting an interaction between SCD and the microbiome that may influence health outcomes.</p><p><strong>Importance: </strong>The oral and nasal cavities are susceptible to environmental exposures including pathogenic microbes. In individuals with systemic disorders, antibiotic exposure, changes to the immune system, or changes to organ function could influence the composition of the microbes at these sites and the overall health of individuals. Children with sickle cell disease (SCD) commonly experience respiratory infections, such as pneumonia or sinusitis, and may have increased susceptibility to infection because of disrupted microbiota at these body sites. We found that children with SCD (cwSCD) had more pathobiont bacteria in the nasal cavity and reduced bacterial diversity in the oral cavity compared to their healthy siblings. Defining when, why, and how these changes occur in cwSCD could help identify specific microbial signatures associated with susceptibility to infection or adverse outcomes, providing insights into personalized treatment strategies and preventive measures.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0013725"},"PeriodicalIF":3.7,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972379","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 : 2025-06-25Epub Date: 2025-05-13DOI: 10.1128/msphere.00913-24
Sromona D Mukherjee, Mangesh Suryavanshi, John Knight, Dirk Lange, Aaron W Miller
{"title":"Metagenomic and phylogenetic analyses reveal gene-level selection constrained by bacterial phylogeny, surrounding oxalate metabolism in the gut microbiota.","authors":"Sromona D Mukherjee, Mangesh Suryavanshi, John Knight, Dirk Lange, Aaron W Miller","doi":"10.1128/msphere.00913-24","DOIUrl":"10.1128/msphere.00913-24","url":null,"abstract":"<p><p>The gut microbiota is critical for neutralizing dietary toxins. Oxalate is a toxin commonly produced by plants to deter herbivory and is widely consumed in the human diet. Excess levels of systemic or urinary oxalate increase risk of multiple urologic and cardiometabolic diseases. The current study employed multiple amplicon-based and shotgun metagenomic methodologies, alongside comparative phylogenetic analyses, to interrogate evolutionary radiation surrounding microbial oxalate degradation within the human gut microbiome. In conservative genome-based estimates, over 30% of gut microbial species harbored at least one oxalate-handling gene, with the specific pathways used dependent on bacterial phylum. Co-occurrence analyses revealed interactions between specialist genes that can metabolize oxalate or its by-products, but not multi-functional genes that can act in more than one oxalate-related pathway. Specialization was rare at the genome level. Amplicon-based metagenomic sequencing of the oxalate-degrading gene, formyl-CoA transferase (<i>frc</i>), coupled with molecular clock phylogenetic analyses are indicative of rapid evolutionary divergence, constrained by phylum. This was corroborated by paired analyses of non-synonymous to synonymous substitutions (dN/dS ratios), which pointed toward neutral to positive selection. Sequence similarity network analyses of <i>frc</i> sequences suggest extensive horizontal gene transferring has occurred with the <i>frc</i> gene, which may have facilitated rapid divergence. The <i>frc</i> gene was primarily allocated to the Pseudomonodota phylum, particularly the <i>Bradyrhizobium</i> genus, which is a species capable of utilizing oxalate as a sole carbon and energy source. Collectively evidence provides strong support that, for oxalate metabolism, evolutionary selection occurs at the gene level, through horizontal gene transfer, rather than at the species level.IMPORTANCEA critical function of the gut microbiota is to neutralize dietary toxins, such as oxalate, which is highly prevalent in plant-based foods and is not degraded by host enzymes. However, little is known about the co-evolutionary patterns of plant toxins and the mammalian gut microbiota, which are expected to exhibit features of an evolutionary arms race. In the current work, we present molecular evidence that microbial genes for oxalate degradation are highly prevalent in humans, potentially driven by extensive horizontal gene transfer events. Phylogenetic analyses reveal that oxalate-degrading genes are under a positive selection pressure and have historically undergone rapid diversification events, which has led to diverse ecological strategies for handling oxalate by gut bacteria. Collectively, data shed light on potential evolutionary relationships between the diet and the gut microbiota that occur relatively independently of the mammalian host.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0091324"},"PeriodicalIF":3.7,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033200","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}