mSphere最新文献

{"title":"Rhizosphere-colonizing bacteria persist in the protist microbiome.","authors":"Stephen J Taerum, Ravikumar R Patel, Justin E Alamo, Daniel Gage, Blaire Steven, Lindsay R Triplett","doi":"10.1128/msphere.00037-25","DOIUrl":"10.1128/msphere.00037-25","url":null,"abstract":"<p><p>Soils contain diverse predatory protists that affect the abundance and behavior of rhizosphere bacteria, including bacteria that may benefit plant health. Protists harbor their own bacterial microbiomes, and we previously observed that plants inoculated with protists harbored rhizosphere bacteria similar to those in the protist inoculum. To determine how protist microbiomes affect the rhizosphere, we profiled the bacteria of eight diverse rhizosphere protist isolates after 2 years of laboratory culture. We then compared the protist culture microbiomes to maize rhizosphere communities 6 weeks after protist inoculation. Introduction of protists enriched 13 protist-associated bacterial amplicon sequence variants (ASVs) in the rhizosphere, which comprised ~10% of the rhizosphere bacterial community. Additional bacterial ASVs ranked highly in abundance in both rhizosphere (top 100) and protist (top 20) microbiomes; together, a median 47% of the protist microbiome was enriched or in high rank abundance in the rhizosphere. Inoculation with three out of eight protist cultures positively affected root biomass traits, but a protist mixture had no effect, indicating that the impact of protist-associated bacteria on plant growth is context dependent. Isolates of protist-associated bacteria had both positive and negative effects on protist growth in culture, suggesting that the bacteria use multiple strategies to survive in proximity to predators. This study demonstrates that even after long-term laboratory culture, rhizosphere protist cultures host bacteria that can colonize the rhizosphere of maize. The findings also identify diverse groups of rhizosphere-colonizing bacteria that persist among protist predators, which suggests that these bacteria could associate with or benefit from protists in the soil.</p><p><strong>Importance: </strong>Understanding the impact of predatory protists on the plant microbiome will be essential to deploy protists in sustainable agriculture. This study shows that eight rhizosphere protist isolates hosted diverse and distinct bacterial communities and that a large proportion of these bacteria could be found colonizing the maize root environment 6 weeks after protists were inoculated onto seedlings. This study demonstrates that certain bacteria from the maize rhizosphere can persist for years in protist cultures and retain the ability to colonize rhizosphere soil, suggesting that protists might support the survival of these rhizosphere bacteria in the absence of the plant.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0003725"},"PeriodicalIF":3.7,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037475","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":"Antibiofilm properties of 4-hydroxy-3-methyl-2-alkenylquinoline, a novel <i>Burkholderia</i>-derived alkaloid.","authors":"McKinley D Williams, Taylor R Sweeney, Sabrina Trieu, Ravi Orugunty, Abdelahhad Barbour, Fereshteh Younesi, Michael Glogauer, Nopakorn Hansanant, Ronald Shin, Shi-En Lu, Kevin Cao, Abraham Tenorio, Sigmund J Haidacher, Anthony M Haag, Thomas D Horvath, Leif Smith","doi":"10.1128/msphere.01081-24","DOIUrl":"10.1128/msphere.01081-24","url":null,"abstract":"<p><p>Biofilms are an important colonization mechanism employed by several microbial species to better establish themselves and monopolize the acquisition of resources across different environs. Some bacteria have evolved specialized metabolites that, when secreted, disrupt the formation and stability of biofilms generated by competing heterospecies, providing the producing organism with an ecological advantage. Soil-derived species are probable candidates for the identification of such compounds, given the intense level of competition that occurs within the terrestrial ecosystem. The MS14 strain of <i>Burkholderia contaminans</i> isolated from soil in Mississippi has previously been shown to produce antimicrobial compounds like occidiofungin and ornibactin. In this report, we demonstrate that this strain also produces 4-hydroxy-3-methyl-2-alkenylquinoline (HMAQ-7), an alkaloid-based metabolite structurally similar to others produced by <i>Burkholderia</i>. HMAQ-7 was isolated and purified in sufficient quantities to enable the elucidation of its covalent structure and the evaluation of its biological effects. The compound was found to possess a unique ability to inhibit biofilm biosynthesis in several species, including opportunistic pathogens like <i>Staphylococcus haemolyticus</i> and within saliva-derived multispecies biofilms. HMAQ-7 also demonstrated an ability to modulate additional cellular behaviors in <i>Bacillus subtilis,</i> including motility and sporulation, suggesting that this molecule is important to the interspecies dynamics present across many diverse microenvironments.IMPORTANCEThe present study furthers our understanding of the structural complexity and the biological functions of the 2-alkyl-4(1H)-quinolone metabolites produced by <i>Burkholderia</i> spp. Low micromolar concentrations of HMAQ-7' induced observable bacterial growth morphology differences. The antibiofilm properties of the HMAQ-7' characterized in this study will promote future investigations into possible biological and applied roles. The ability to alter biofilm formation using HMAQ-7' may facilitate <i>Burkholderia</i> spp. colonization in a multitude of environments, that is, aquatic, soil, and possibly during infection. HMAQ may subvert competition by potential competitor species in natural environments of <i>Burkholderia</i> spp. and possibly lung infections of cystic fibrosis patients.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0108124"},"PeriodicalIF":3.7,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009033","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":"Using host and bacterial genetic approaches to define virulence strategies and protective immunity during <i>Mycobacterium tuberculosis</i> infection.","authors":"Andrew J Olive","doi":"10.1128/msphere.00517-24","DOIUrl":"10.1128/msphere.00517-24","url":null,"abstract":"<p><p>Infections with <i>Mycobacterium tuberculosis</i> (Mtb) resulted in over one million deaths in 2024, the highest number for any infectious disease. With no vaccines that protect against pulmonary tuberculosis (TB) and the challenges associated with antibiotic therapy, there is a critical need to better understand host-Mtb interactions to help curb this major public health problem. Mtb is arguably the most successful human pathogen, and it survives in diverse environments, resulting in heterogeneous disease outcomes in patients. Five years ago, in my commentary in mSphere, I discussed how Mtb virulence strategies that sense, adapt, and evade killing in the host can be uncovered using genetic approaches. Here, I will come full circle to highlight genetic approaches that recently uncovered new mechanisms regulating protective host responses and Mtb survival tactics. The goal is to highlight a genetic framework to probe a range of unexplored Mtb phenotypes, increase our understanding of host-Mtb interactions, and identify new therapeutic targets that may help prevent TB.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0051724"},"PeriodicalIF":3.7,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028822","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":"Toward a deeper understanding of dengue: novel method for quantification and isolation of envelope protein epitope-specific antibodies.","authors":"Sokchea Lay, Candice Bohaud, Sopheak Sorn, Sreymom Ken, Felix A Rey, Kevin K Ariën, Sowath Ly, Veasna Duong, Giovanna Barba-Spaeth, Heidi Auerswald, Tineke Cantaert","doi":"10.1128/msphere.00961-24","DOIUrl":"10.1128/msphere.00961-24","url":null,"abstract":"<p><p>The dengue viruses (DENV) envelope (E) protein is the main target of the antibody (Ab) response. Abs target different epitopes on the E-protein, including sE-dimer, E domain III (EDIII), and fusion loop (FL). Anti-EDIII Abs are mainly serotype-specific, whereas anti-FL Abs can induce antibody-dependent enhancement (ADE) <i>in vitro</i>. Abs targeting sE-dimer epitopes can cross-neutralize different DENV serotypes. However, the involvement of each Ab subset in disease pathogenicity and/or protection remains unclear. We aimed to optimize the quantification and purification of DENV E-protein epitope-specific Abs from human samples. C-terminal biotinylated DENV2 E recombinant proteins (EDIII, soluble E [sE], and sE-dimer) were coupled to color-coded magnetic microspheres for a multiplex immunoassay (MIA), testing different antigen concentrations. Assay performance was evaluated using well-characterized anti-DENV monoclonal antibodies (mAbs) and total IgG from DENV seronegative and seropositive human plasma. Specific FL epitopes were blocked with mouse mAb clone 4G2 to quantify anti-FL- and sE-dimer-specific Abs, measuring antigen-antibody reactions as median fluorescence intensity (MFI). For isolation of E-protein epitope-specific antibodies, sE-proteins were conjugated to streptavidin resin beads. Total IgG from human plasma was incubated with immobilized EDIII to elute anti-EDIII Abs. The flow-through was incubated with sE-dimer resin beads to elute sE-dimer specific Ab enriched fraction, and the flow-through was applied to immobilized sE to elute anti-FL Abs. In conclusion, we have developed a serological assay to detect E-protein epitope-specific Abs in DENV-infected humans. Additionally, we successfully isolated anti-EDIII, anti-FL, and an enriched fraction of sE-dimer specific Abs from human samples.IMPORTANCEThe development of effective dengue virus (DENV) vaccines has been hampered by limited insights into the immunological mechanisms of protection. Our study addresses this gap by introducing a refined multiplex microsphere-based immunoassay (MIA) to quantify and isolate antibodies (Abs) targeting specific E-protein epitopes, such as E domain III (EDIII), the fusion loop (FL), and the sE-dimer specific Abs. This method provides detailed epitope-specific Ab profiling with high sensitivity and requires minimal sample volumes. The ability to isolate specific Ab subsets from human plasma also enables detailed investigations into their roles in protection or pathogenesis, paving the way for more effective dengue interventions.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0096124"},"PeriodicalIF":3.7,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991362","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":"Characterization of a novel <i>Leishmania</i> antigen containing a repetitive domain and its potential use as a prophylactic and therapeutic vaccine.","authors":"Bianca de Oliveira, Wanessa M Goes, Frederico C Nascimento, Juliana B T Carnielli, Eden R Ferreira, Alex Fiorini de Carvalho, Pablo Victor Mendes Dos Reis, Milton Pereira, Tiago Queiroga Nery Ricotta, Liliane Martins Dos Santos, Renan Pedra de Souza, Diego Esteban Cargnelutti, Jeremy C Mottram, Santuza R Teixeira, Ana Paula Fernandes, Ricardo T Gazzinelli","doi":"10.1128/msphere.00097-25","DOIUrl":"10.1128/msphere.00097-25","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Human visceral leishmaniasis (HVL) is the second most lethal tropical parasitic disease. Currently, no prophylactic or therapeutic vaccines exist for HVL. Thus, the development of an efficacious vaccine is still needed. We previously performed an immunoproteomics analysis on &lt;i&gt;Leishmania amazonensis&lt;/i&gt; parasite extracts to identify immunodominant antigens recognized by the sera of vaccinated and protected mice. Among the identified antigens, we discovered a novel, previously unstudied repetitive protein, initially annotated in &lt;i&gt;Leishmania&lt;/i&gt; genomes as a kinetoplast-associated protein-like protein from &lt;i&gt;Leishmania infantum&lt;/i&gt; (LinKAP), containing conserved domains (trichohyalin-plectin-homology [TPH] and TolA) that are associated with other mitochondrial proteins. LinKAP sequences are conserved across trypanosomatids, including &lt;i&gt;Endotrypanum, Leishmania,&lt;/i&gt; and &lt;i&gt;Trypanosoma&lt;/i&gt; species. Using differential centrifugation of &lt;i&gt;Leishmania&lt;/i&gt; subcellular structures, we showed that LinKAP was enriched in fractions colocalizing with other mitochondrial proteins. mNeonGreen labeling at the endogenous locus using CRISPR-Cas9 and confocal microscopy confirmed that LinKAP is a mitochondrial-associated protein in &lt;i&gt;Leishmania&lt;/i&gt; but not specifically colocalized with kDNA. We cloned and expressed a truncated version of LinKAP (rLinKAP), containing part (15) of the several LinKAP amino acid repeats, demonstrating over 85% homology across &lt;i&gt;L. infantum, L. amazonensis, L. braziliensis,&lt;/i&gt; and &lt;i&gt;L. mexicana&lt;/i&gt; species. An adjuvanted formulation of LinKAP with Poly ICLC, a polyinosinic-polycytidylic acid (Poly I:C) stabilized with carboxymethylcellulose and polylysine, was used to vaccinate mice and hamsters as a prophylactic vaccine for visceral leishmaniasis. Animals immunized with rLinKAP showed a potent cellular and humoral response and a significant decrease in tissue parasitism when challenged with &lt;i&gt;L. infantum&lt;/i&gt;. We also tested rLinKAP as a therapeutic vaccine in mice. Following therapeutic vaccination, antibody responses were enhanced, and cellular responses became apparent. Our treatment protocol inhibited splenic parasite burden by 75% in treated mice. In conclusion, our antigen discovery strategy and the observed protective effect highlight rLinKAP as a promising vaccine candidate for leishmaniasis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;A previous reverse vaccinology study identified kinetoplast-associated protein-like protein from &lt;i&gt;Leishmania infantum&lt;/i&gt; (LinKAP) as a potential new vaccine target, as this protein was recognized by the sera of protected mice in extracts of &lt;i&gt;Leishmania&lt;/i&gt; promastigotes. Interestingly, LinKAP is a repetitive protein containing trichohyalin-plectin-homology (TPH) and TolA domains and was initially annotated as a kinetoplast-associated protein. We further characterized LinKAP as a mitochondrial-associated protein highly conserved among trypanosomatids. We also validated LinKAP as a promis","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0009725"},"PeriodicalIF":3.7,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064161","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":"Pear flower and leaf microbiome dynamics during the naturally occurring spread of <i>Erwinia amylovora</i>.","authors":"Aia Oz, Orly Mairesse, Shira Raikin, Hila Hanani, Hadar Mor, Mery Dafny Yelin, Itai Sharon","doi":"10.1128/msphere.00011-25","DOIUrl":"10.1128/msphere.00011-25","url":null,"abstract":"<p><p><i>Erwinia amylovora</i> is the causal pathogen of fire blight, a contagious disease that affects apple and pear trees and other members of the family Rosaceae. In this study, we investigated the community dynamics of the pear flower microbiome in an agricultural setting during the naturally occurring infection of <i>E. amylovora</i>. Five potential factors were considered: collection date, the flower's phenological stage, location on the tree, location within the orchard, and pear cultivar. The phenological stage and the collection date were identified as the most important factors associated with pear flower microbiome composition, while the location of the tree in the orchard and the flower's location on the tree had a marginal effect. The leaf microbiome reflected that of the abundant phenological stage on each date. The flower microbiome shifted toward <i>E. amylovora</i> dominating the community as time and phenological stages progressed, leading to a decreased community diversity. The <i>E. amylovora</i> population was represented almost exclusively by six amplicon sequence variants (ASVs) with similar proportions throughout the entire collection period. Other taxa, including <i>Pseudomonas</i>, <i>Pantoea</i>, <i>Lactobacillus</i>, and <i>Sphingomonas</i>, were represented by dozens of ASVs, and different succession patterns in their populations were observed. Some of the taxa identified include known antagonists to <i>E. amylovora</i>. Overall, our results suggest that flower physiology and the interaction with the environment are strongly associated with the pear flower microbiome and should be considered separately. Taxon-specific succession patterns under <i>E. amylovora</i> spread should be considered when choosing candidates for antagonist-based treatments for fire blight.IMPORTANCEThe spread of pathogens in plants is an important ecological phenomenon and has a significant economic impact on agriculture. Flowers serve as the entry point for <i>E. amylovora,</i> but members of the flower microbiome can inhibit or slow down the proliferation and penetration of the pathogen. Knowledge about leaf and flower microbiome response to the naturally occurring spread of <i>E. amylovora</i> is still lacking. The current study is the first to describe the Rosaceae flower microbiome dynamics during the naturally occurring infection <i>of E. amylovora</i>. Unlike previous studies, the study design enabled us to evaluate the contribution of five important environmental parameters to community composition. We identified different ASV succession patterns across different taxa in the flower consortia throughout the season. These results contribute to our understanding of plant microbial ecology during pathogen spread and can help improve biological treatments for fire blight.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0001125"},"PeriodicalIF":3.7,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037472","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":"Adaptation of the tetracycline-repressible system for modulating the expression of essential genes in <i>Cryptococcus neoformans</i>.","authors":"Ci Fu, Nicole Robbins, Leah E Cowen","doi":"10.1128/msphere.01018-24","DOIUrl":"10.1128/msphere.01018-24","url":null,"abstract":"<p><p>The opportunistic human fungal pathogen <i>Cryptococcus neoformans</i> has an enormous impact on human health as the causative agent of cryptococcal meningitis, and there is a dire need to expand our current antifungal arsenal. Essential gene products often serve as ideal targets for antimicrobials, and identifying and characterizing essential genes in a pathogen of interest is critical for drug development. Unfortunately, characterization of essential genes in <i>C. neoformans</i> is limited due to its haploid nature and lack of genetic tools for generating effective conditional-expression mutants. To date, the copper-repressible promoter <i>pCTR4</i> is the most widely used system to regulate essential gene expression; however, its expression is leaky and copper has pleiotropic effects. In diverse fungal species, including <i>Saccharomyces cerevisiae</i>, <i>Candida albicans</i>, and <i>Candida auris</i>, the tetracycline-repressible promoter system is a powerful tool to regulate gene expression; however, it has yet to be adapted for <i>C. neoformans</i>. In this study, we successfully implemented the tetracycline-repressible system in <i>C. neoformans</i> to regulate the expression of the essential genes <i>HSP90</i> and <i>FKS1</i>. Supplementation of cultures with the tetracycline analog doxycycline efficiently depleted <i>HSP90</i> at both transcript and protein levels and inhibited <i>C. neoformans</i> growth and viability. Similarly, the depletion of <i>FKS1</i> with doxycycline enhanced sensitivity of the strain to the echinocandin caspofungin, an antifungal that targets the glucan synthase but is generally ineffective against <i>C. neoformans</i>. Thus, this work unveils a novel approach to generate conditional-expression mutants in <i>C. neoformans,</i> providing unprecedented potential to systematically study essential gene function in this important human fungal pathogen.IMPORTANCEInvasive fungal infections cause millions of deaths annually, while the number of antifungals available to combat these pathogens is limited to only three classes: polyenes, azoles, and echinocandins. The largest source of novel antifungal drug targets are essential gene products, which are required for cellular viability. However, tools to identify and characterize essential genes in <i>C. neoformans</i> are extremely limited. Here, we adapted the tetracycline-repressible promoter system, that has been widely used in other organisms, to study essential gene function in <i>C. neoformans</i>. By placing this regulatable promoter upstream of the essential genes <i>HSP90</i> and <i>FKS1</i>, we confirmed that the growth of the strains in the presence of the tetracycline analog doxycycline results in the depletion of essential gene expression. This approach provides a significant advance for the systematic study of essential genes in <i>C. neoformans</i>.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0101824"},"PeriodicalIF":3.7,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973522","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":"Risk of death during acute infection is accelerating across diverse host-pathogen systems and consistent with multiple models of host-pathogen interaction.","authors":"Tim O'Sullivan, Canan Karakoç, Kristofer Wollein Waldetoft, Sam P Brown","doi":"10.1128/msphere.00953-24","DOIUrl":"10.1128/msphere.00953-24","url":null,"abstract":"<p><p>Infectious diseases remain a major cause of global mortality, yet basic questions concerning the relationship between within-host processes governing pathogen burden (pathogen replication, immune responses) and population-scale (epidemiological) patterns of mortality remain obscure. We use a structured literature review to leverage the extensive biomedical data generated by controlled host infections to address the epidemiological question of whether infection-induced mortality is constant, accelerating, or follows some other pattern of change and to infer the within-host mechanistic basis of this pattern. We show that across diverse lethal infection models, the risk of death increases approximately exponentially in time since infection, in a manner phenomenologically similar to the dynamics of all-cause death. We further show that this pattern of accelerating risk is consistent with multiple alternate mechanisms of pathogen growth and host-pathogen interaction, underlining the limitations of current experimental approaches to connect within-host processes to epidemiological patterns. We review critical experimental questions that our work highlights, requiring additional non-invasive data on pathogen burden throughout the course of infection.IMPORTANCEHere, we ask a simple question: what are the dynamics of pathogen-induced death? Death is a central phenotype in both biomedical and epidemiological infectious disease biology, yet very little work has attempted to link the biomedical focus on pathogen dynamics within a host and the epidemiological focus on populations of infected hosts. To systematically characterize the dynamics of death in controlled animal infections, we analyzed 209 data sets spanning diverse lethal animal infection models. Across experimental models, we find robust support for an accelerating risk of death since the time of infection, contrasting with conventional epidemiological models that assume a constant elevated risk of death. Using math models, we show that multiple processes of growth and virulence are consistent with accelerating risk of death, and we end with a discussion of critical experiments to resolve how within-host biomedical processes map onto epidemiological patterns of disease.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0095324"},"PeriodicalIF":3.7,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036083","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":"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":"10.1128/msphere.00041-25","url":null,"abstract":"","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0004125"},"PeriodicalIF":3.7,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12039219/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Variable phylosymbiosis and cophylogeny patterns in wild fish gut microbiota of a large subtropical river.","authors":"Yaqiu Liu, Xinhui Li, Konstantinos Ar Kormas, Yuefei Li, Huifeng Li, Jie Li","doi":"10.1128/msphere.00982-24","DOIUrl":"10.1128/msphere.00982-24","url":null,"abstract":"<p><p>The persistence and specificity of fish host-microbial interaction during evolution is an important part of exploring the host-microbial symbiosis mechanism. However, it remains unclear how the environmental and host factors shape fish host-microbe symbiotic relationships in subtropical rivers with complex natural environments. Freshwater fish are important consumers in rivers and lakes and are considered keystone species in maintaining the stability of food webs there. In this study, patterns and mechanisms shaping gut microbiota community in 42 fish species from the Pearl River, in the subtropical zone of China, were investigated. The results showed that fish host specificity is a key driver of gut microbiota evolution and diversification. Different taxonomic levels of the host showed different degrees of contribution to gut microbiota variation. Geographical location and habitat type were the next most important factors in shaping gut microbiota across the 42 fishes, followed by diet and gut trait. Our results emphasized the contribution of stochastic processes (drift and homogenizing dispersal) in the gut microbial community assembly of freshwater fishes in the middle and lower reaches of the Pearl River. Phylosymbiosis is evident at both global and local levels, which are jointly shaped by complex factors including ecological or host physiological filtration and evolutionary processes. The core microbiota showed co-evolutionary relationships of varying degrees with different taxonomic groups. We speculate that host genetic isolation or habitat variation facilitates the heterogeneous selection (deterministic process), which occurs and results in different host-core bacterium specificity.</p><p><strong>Importance: </strong>Freshwater fish are regarded as the dominant consumers in rivers and lakes. Due to their diverse feeding modes, fish significantly enhance the trophic link and nutrient recycling/retention in aquatic habitats. For this, they are often considered keystone species in maintaining the stability of food webs in rivers and lakes. A significant part of fish nutrition is essentially mediated by their gut microbiota, which can enhance fish tolerance to fluctuations in external resources and improve the efficiency of nutrients extracted from various food sources. As gut bacterial symbionts have a profound impact on the nutrition and development of their hosts, as well as their overall fitness, it is critical to answer the question of how hosts maintain these benefits by procuring or inheriting these vital symbionts, which is still largely unanswered, especially for freshwater fish. Our study provides new insights into the co-evolutionary relationship between wild fish and their symbiotic microbiome, the hidden diversity of gut microbiome, and the ecological adaptation potential of wild freshwater fish.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0098224"},"PeriodicalIF":3.7,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12039269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731036","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}