mSystems最新文献

{"title":"Non-genetic red blood cell variability can modulate hemoglobin consumption by intracellular <i>Plasmodium falciparum</i>.","authors":"Joseph R Perko, Abhyudai Singh, Secilia I Lopez, Armando Estrada, Shweta Singh, Janice M Moser, Kelly Haupfear, George J Klarmann, Sabrina J Tuson, Vincent B Ho, Shirley Luckhart, Andreas E Vasdekis","doi":"10.1128/msystems.00554-26","DOIUrl":"https://doi.org/10.1128/msystems.00554-26","url":null,"abstract":"<p><p>Natural, non-genetic variation among host cells can shape infection outcomes, yet its role in intracellular parasite dynamics remains poorly understood. Here, we show that variability in hemoglobin (Hb) content among individual red blood cells (RBCs) modulates nutrient consumption by <i>Plasmodium falciparum</i>, the most lethal malaria parasite. Using label-free quantitative-phase imaging (QPI), we measured cytosolic Hb in thousands of uninfected and infected RBCs across the 48-h asexual cycle. Hb content varied widely among uninfected cells, and after invasion, infected cells mirrored and amplified this distribution: variability increased from 17% in uninfected RBCs to >100% in schizonts. A minimal predator-prey model accurately reproduced the observed spread in parasite Hb consumption, showing that host variability alone can generate much of the diversity in parasite feeding rates traditionally attributed to parasite factors. These findings provide the first evidence that host phenotypic noise drives variation in Hb consumption among genetically identical parasites. Incorporating host-to-host variability into within-host models could improve predictions of parasite growth, refine the activation kinetics of Hb-dependent antimalarials, and reveal analogous principles in other intracellular infections where host variability and host-parasite crosstalk can shape pathogen outcomes. This systems-level perspective emphasizes the need to account for host heterogeneity in both experimental design and therapeutic strategies.IMPORTANCECell-to-cell phenotypic variability is a fundamental feature of living systems, yet its impact on host-pathogen interactions has been largely overlooked. Here, we show that natural, non-genetic variation in red blood cell hemoglobin strongly shapes how <i>Plasmodium falciparum</i>-the most lethal malaria parasite-consumes Hb inside host cells. Using quantitative imaging and a mathematical model, we demonstrate that host variability alone can explain much of the observed differences in parasite feeding rates. This perspective reframes parasite Hb consumption as an emergent property of host-parasite interactions. More broadly, it highlights how natural variability among host cells can influence the course of intracellular infections, with potential implications for predicting pathogen growth and optimizing drug treatment strategies.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0055426"},"PeriodicalIF":5.2,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891895","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":"Chloramphenicol stress triggers oxidative adaptation in <i>Acinetobacter baumannii</i> ATCC19606 devoid of RND efflux pumps AdeAB or AdeIJ.","authors":"Wuen Ee Foong, Xinxin Xiang, Wenjun He, Xuan Yan, Jiabin Huang, Klaas M Pos, Heng-Keat Tam","doi":"10.1128/msystems.00009-26","DOIUrl":"https://doi.org/10.1128/msystems.00009-26","url":null,"abstract":"<p><p>Efflux pumps play a key role in both intrinsic and acquired antibiotic resistance in <i>Acinetobacter baumannii</i>, yet their broader physiological roles remain unclear. Here, we investigated the transcriptomic and phenotypic responses of <i>A. baumannii</i> ATCC19606 mutants lacking the efflux pumps AdeAB, AdeIJ, or CraA under chloramphenicol stress. The deletion of <i>craA</i> resulted in a 32-fold reduction in chloramphenicol MIC, while Δ<i>adeIJ</i> showed a modest 4-fold decrease, and Δ<i>adeAB</i> had no effect on chloramphenicol susceptibility. Transcriptomic profiling revealed minimal alterations in Δ<i>craA</i>, but notable transcriptional reprogramming in Δ<i>adeAB</i> and Δ<i>adeIJ</i>, including upregulation of ribosomal genes, iron-sulfur cluster biogenesis, aromatic compound catabolism, and amino acid transport systems. Under chloramphenicol stress, Δ<i>adeAB</i> exhibited metabolic remodeling, activating oxidative stress defenses and protein quality control pathways while repressing type VI secretion. Both Δ<i>adeIJ</i> and wild-type strains upregulated arginine and glutamate metabolism, likely contributing to redox balance. Phenotypically, the Δ<i>adeIJ</i> strain showed elevated basal and H₂O₂-induced ROS levels, as well as heightened sensitivity to nitrosative stress and Cu²⁺, which may suggest a role for AdeIJ in oxidative and metal stress responses. Despite increased <i>adeAB</i> and <i>craA</i> expression under chloramphenicol stress, only <i>craA</i> deletion significantly impaired resistance, highlighting its dominant role in chloramphenicol efflux. Collectively, our findings reveal efflux pump-specific and strain-specific adaptations to antibiotic stress, positioning CraA as a major determinant of chloramphenicol resistance, while RND transporters such as AdeABC and AdeIJK may also be associated with broader stress adaptation processes, including redox and metal homeostasis, in <i>A. baumannii</i>.IMPORTANCEEfflux pumps are key drivers of multidrug resistance in <i>Acinetobacter baumannii</i>, yet their broader roles in stress adaptation remain insufficiently understood. Here, we show that the loss of major efflux systems reshapes the transcriptomic and metabolic landscape under chloramphenicol stress, a condition that also imposes oxidative stress. In particular, the RND efflux pump AdeIJK may be linked to alterations in cellular responses to oxidative, nitrosative, and metal stress, although the mechanistic basis of this interplay remains to be further investigated. Overall, these findings suggest that efflux pumps may contribute to bacterial resilience beyond drug resistance, providing additional insight into efflux system hierarchy and functional redundancy in <i>A. baumannii</i>, and may inform future studies aimed at understanding persistence and efflux-mediated multidrug resistance mechanisms.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0000926"},"PeriodicalIF":5.2,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148888007","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":"Repurposing anti-phage defenses to differentially arrest the viral lifecycle reveals the regulatory logic of a parasitic satellite.","authors":"S Tansu Bagdatli, Kimberley D Seed","doi":"10.1128/msystems.00428-26","DOIUrl":"https://doi.org/10.1128/msystems.00428-26","url":null,"abstract":"<p><p>Mobile genetic elements frequently encode defense mechanisms to protect their bacterial hosts from viral attack. In <i>Vibrio cholerae</i>, these defensive elements include phage-inducible chromosomal island-like elements (PLEs), which are phage satellites that act as highly specialized parasites of the lytic phage ICP1. While PLE transcriptional activation upon ICP1 infection is known to be temporally regulated, the underlying regulatory logic and dependencies on the progression of the phage's developmental program required for activation remain unclear. In this study, we took a novel approach to define these dependencies by introducing independent anti-phage defense systems, BREX and DarTG, as molecular roadblocks to impede the ICP1 lifecycle. We discovered that, for both ICP1 and PLE, late-stage gene expression is fundamentally uncoupled from genome replication, representing a striking departure from the standard paradigm for double-stranded DNA phages. While BREX restricts ICP1 to an immediate-early transcriptional state that stalls PLE activation, DarTG allows the phage to execute its full transcriptional cascade despite the total block in DNA replication. This permissive environment provides the necessary cue(s) for complete PLE induction, revealing that robust PLE activation is profoundly dependent on the transcriptional progression of its helper phage.IMPORTANCEBacteria and their viruses (phages) are locked in perpetual evolutionary conflict. Some bacteria harbor phage satellites, specialized parasites that are activated to hijack the phage's components to spread all the while inhibiting viral production. While some satellites respond to a single viral trigger, the regulation of many satellites, including clinically relevant phage-inducible chromosomal island-like elements (PLEs) in <i>Vibrio cholerae</i>, remains poorly understood. Here, we used bacterial defense systems as molecular roadblocks to probe how PLE activation depends on its helper phage. We found that severe disruptions to viral transcription stall PLE activation. Unexpectedly, both the virus and the satellite can execute their full transcriptional programs even when DNA replication is completely blocked, challenging a fundamental paradigm in virology. These insights reveal a sophisticated level of phage-satellite coordination, illustrating how satellite activation is tightly linked to the transcriptional state of its helper phage, a dependency that ultimately drives the dissemination of mobile genetic elements.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0042826"},"PeriodicalIF":5.2,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148881225","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":"Unlocking the power of <i>Pseudomonas</i>: network-guided isolation enhances plant growth on <i>Achnatherum inebrians</i>.","authors":"Jinjin Liang, Chunjie Li, Xingxu Zhang, Zhibiao Nan","doi":"10.1128/msystems.00563-26","DOIUrl":"https://doi.org/10.1128/msystems.00563-26","url":null,"abstract":"&lt;p&gt;&lt;p&gt;The tripartite interplay among plants, bacteria, and fungal endophytes is crucial for maintaining host plant fitness. However, how &lt;i&gt;Epichloë&lt;/i&gt; endophytes influence plant-associated bacterial communities in cool-season grasses, particularly in ecologically important yet understudied species, such as &lt;i&gt;Achnatherum inebrians&lt;/i&gt;, remains unclear. Using phylogenetic molecular ecological network analysis, we determined that seed-borne (seed epiphytic) and phyllosphere bacterial communities of &lt;i&gt;Epichloë&lt;/i&gt;-infected (EI) &lt;i&gt;A. inebrians&lt;/i&gt; exhibited reduced network complexity compared to &lt;i&gt;Epichloë&lt;/i&gt;-free (EF) plants. Across all samples, Proteobacteria and Firmicutes dominated the keystone taxa, with &lt;i&gt;Pseudomonas&lt;/i&gt; (OTU744 and OTU8264) consistently identified as a hub genus in both seed-borne and phyllosphere networks. Culture-based analysis revealed that endophyte-infected plants had a significantly (&lt;i&gt;P&lt;/i&gt; &lt; 0.05) higher relative abundance of &lt;i&gt;Pseudomonas&lt;/i&gt; and &lt;i&gt;Bacillus&lt;/i&gt; than EF &lt;i&gt;A. inebrians&lt;/i&gt;, especially &lt;i&gt;Pseudomonas&lt;/i&gt; comprised 13, 35, and 33% of isolates from the seed, leaf, and rhizosphere of &lt;i&gt;A. inebrians&lt;/i&gt;, respectively. To capture potential functional diversity, we selected two phylogenetically distant &lt;i&gt;Pseudomonas&lt;/i&gt; strains from each of the three ecological niches for further analysis. Inoculation of &lt;i&gt;A. inebrians&lt;/i&gt; seedlings with these strains consistently promoted plant growth, enhanced forage quality (total nitrogen content), and improved nutritional value (ether extract). Whole-genome sequencing combined core-genome phylogenetic tree of the six &lt;i&gt;Pseudomonas&lt;/i&gt; strains and confirmed that five strains belong to &lt;i&gt;P. atacamensis&lt;/i&gt;, whereas Pse19 was &lt;i&gt;P. cucumis&lt;/i&gt;. Our findings reveal that &lt;i&gt;Epichloë&lt;/i&gt; endophytes modulate bacterial network stability and enrich plant-associated &lt;i&gt;Pseudomonas&lt;/i&gt;, which synergistically enhance host performance. Collectively, this study provides a mechanistic framework for manipulating keystone taxa and beneficial isolates to improve grass productivity in grassland agricultural ecosystems.IMPORTANCEAlthough the tripartite interplay between plants, bacteria, and fungal endophytes, such as &lt;i&gt;Epichloë&lt;/i&gt;, is recognized as vital for host fitness, the specific mechanisms through which these endophytes shape associated bacterial communities, particularly in ecologically significant grasses, such as &lt;i&gt;Achnatherum inebrians&lt;/i&gt;, remain poorly understood. This study provides crucial mechanistic insights by revealing that &lt;i&gt;Epichloë&lt;/i&gt; endophytes reconfigure the structure and stability of both seed-borne and phyllosphere bacterial networks in &lt;i&gt;A. inebrians&lt;/i&gt;, leading to reduced complexity but enrichment of specific keystone taxa. We identify &lt;i&gt;Pseudomonas&lt;/i&gt; as a consistently dominant hub genus across these niches. Notably, functional validation shows that diverse &lt;i&gt;Pseudomonas&lt;/i&gt; isolates, representative of those enriched by the endophyte, s","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0056326"},"PeriodicalIF":5.2,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148881210","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":"Distinct transcription factor network dynamics underlie early and long-term adaptation to rifampicin in <i>Escherichia coli</i>.","authors":"M M Azevedo, A M Arsh, R Jagadeesan, Pooja Ravaria, Andre S Ribeiro","doi":"10.1128/msystems.00808-26","DOIUrl":"https://doi.org/10.1128/msystems.00808-26","url":null,"abstract":"<p><p>When subject to sublethal rifampicin stress, susceptible <i>Escherichia coli</i> cells quickly adapt to increase survival. We investigated whether the transcription factor network contributes to this adaptation. First, a responsive cohort of 709 genes diverged from the control, suggesting strong disturbance. While this was largely a direct effect of rifampicin, we show evidence that RNAP, σ⁷⁰, σ³⁸, Fnr, and (p)ppGpp were influential, suggesting early adaptations. We further show evidence that these responses can be promoter sequence dependent and are partially decoupled from changes in single-cell variability. Moreover, the responses of interacting genes were correlated, suggesting coordination. Later, the transcriptome partially realigned with the control, but 272 genes behaved consistently with long-term adaptation. Several exhibited correlated dynamics that can be explained by interactions, which form three independent, star-like modules of adaptive genes controlled by <i>gcvB</i>, <i>cdaR</i>, and <i>lldR</i>, respectively. Finally, we found that orthologous genes of the evolutionarily distant pathogen <i>Mycobacterium tuberculosis</i> have correlated response strengths to rifampicin, suggesting that our observations may be common across bacterial species. Overall, the results suggest that the initial effects of sublethal rifampicin concentrations on <i>E. coli</i>'s genome-wide transcriptional levels are dampened over time and then followed by a distinct state influenced by the gene network that may contribute to adaptation. These findings may assist in developing new strategies to disrupt bacterial adaptation to rifampicin.In natural environments, exposure to sublethal antibiotic (AB) stress is a common phenomenon that enhances the emergence of AB resistance. We dissected the genome-wide transcriptional program of <i>Escherichia coli</i> responsible for its initial response and subsequent adaptation to rifampicin. We show that the transcription factor network plays a major role in this program and provide evidence that the transcriptome response patterns are conserved in the evolutionarily distant pathogen <i>Mycobacterium tuberculosis</i>. Our findings may assist in developing new strategies to disrupt bacterial adaptation to rifampicin.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0080826"},"PeriodicalIF":5.2,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148881197","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":"Multi-kingdom gut microbiota analyses identify biomarkers of different types of pediatric short bowel syndrome.","authors":"Qing-Qing Wu, Cheng-Yong Li, Shan-Shan Chen, Juan Xu, Wei-Hui Yan, Li-Na Lu, Hai-Xia Feng, Jin-An Zhou, Lu Wang, Ning-Ning Liu, Lu Jiang, Ying Wang","doi":"10.1128/msystems.00316-26","DOIUrl":"10.1128/msystems.00316-26","url":null,"abstract":"<p><p>Despite recent advances in bacterial profiling across the three anatomical types of pediatric short bowel syndrome (SBS), the gut multi-kingdom remains unexplored. We characterized the four-kingdom gut microbiota using modified DNA extraction and deep shotgun metagenomic sequencing of fecal samples from 26 healthy controls and 34 pediatric SBS patients comprising three types (8 SBS I, 15 SBS II, and 11 SBS III). Overall, children with SBS exhibited a significant reduction in α-diversity compared with controls, with no difference observed among SBS types. Compared with controls, the proportion of archaea was significantly decreased in all SBS types, while bacteria, fungi, and viruses remained similar across types. Different types of SBS exhibited distinct microbial signatures: SBS I was enriched with pathogens (such as species from the <i>Streptococcus</i> and <i>Klebsiella</i> genera); SBS II was marked by a depletion of beneficial short-chain fatty acid-producing species (such as <i>Faecalibacterium prausnitzii</i>); and SBS III displayed loss of bile acid-metabolizing species, alongside a significant expansion of <i>Lactobacillus</i> species. Ecological networks were rewired in SBS, with disruption pronounced in SBS I. Functional analysis revealed that core metabolic pathways were markedly suppressed in SBS I compared with controls. Integrated correlation analyses revealed ileocecal valve loss as the primary determinant of SBS I microbial profiles, linking it to impaired secretory functions and hepatic injury. Our findings deciphered type-specific alterations in the multi-kingdom microbiota and their functional profiles, providing the basis for designing precision microbial therapies aimed at improving long-term outcomes for children with SBS.IMPORTANCEPediatric short bowel syndrome (SBS) is a primary cause of intestinal failure, yet prior research characterizing the gut microbiota has focused almost exclusively on bacteria. In this study, we characterized the multi-kingdom microbiome (including bacteria, fungi, archaea, and viruses) across the three anatomical types of pediatric SBS. We found that different SBS subtypes showed distinct microbial patterns: SBS I was enriched in pathogens, SBS II exhibited a depletion of beneficial short-chain fatty acid-producing species, and SBS III was characterized by a loss of bile acid-metabolizing microbes with an expansion of <i>Lactobacillus</i>. Functional analysis showed that SBS I had markedly suppressed core metabolic pathways, and integrated analyses identified the ileocecal valve as a key determinant of microbial gene profiles, with its loss linked to impaired secretion and liver injury. These findings provide a comprehensive multi-kingdom view of the pediatric SBS microbiome and highlight anatomical determinants shaping host-microbiome dysfunction.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0031626"},"PeriodicalIF":5.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865882","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":"Global and local trajectories of infant gut microbiota development in Bangladesh across the COVID-19 pandemic.","authors":"Maria Ioanna Papadaki, Gwen Falony, Sara Vieira-Silva, Raul Yhossef Tito, Leen Rymenans, Jill Swinnen, Lila Close, Jara Wagemans, Shafina Jahan, Muntasir Alam, Kamrun Nahar, Mustafizur Rahman, Jeroen Raes, Jelle Matthijnssens","doi":"10.1128/msystems.00101-26","DOIUrl":"10.1128/msystems.00101-26","url":null,"abstract":"<p><p>The establishment of the gut microbiota in early life is fundamental to lifelong health, yet this process remains poorly explored outside Western and high-income settings. We investigated microbial maturation in a non-Western context, by longitudinally characterizing the gut microbiota of 20 healthy infants from urban Bangladesh (<i>n</i> = 984 fecal samples) across the first 2 years of life. Microbiota development followed a three-staged successional pattern characterized by a progressive increase of microbiota diversity, closely resembling patterns described in Western populations. Comparative analysis with a Belgian infant cohort showed broadly conserved maturation dynamics but population-specific differences in core bacteria, including <i>Segatella</i>, which was characteristic of Bangladeshi infants. <i>Segatella</i>'s role in the developing gut remains unclear, as high abundances were associated with disease in this cohort. Transient disruptions in maturation also coincided with episodes of illness. The second year of this cohort coincided with the onset of the COVID-19 pandemic where differences in the relative abundance of several key taxa were detected. These insights expand our understanding of healthy infant gut microbiota development across populations and emphasize the need to consider sociocultural and environmental factors, including global disruptions, in shaping early-life microbial ecosystems.The first years of life represent a critical period during which the gut microbiota is established, with lasting implications for long-term health. However, current knowledge of this process is derived largely from studies conducted in Western and high-income populations even though gut microbiota composition is known to vary across geographic locations. In this study, we longitudinally characterized the gut microbiota development in a healthy infant cohort from urban Bangladesh, showing that geographically distinct populations can harbor different microbial communities while following similar developmental patterns. We further observe that illness can temporarily influence microbiota maturation, and that part of the microbiota maturation period in this cohort overlapped with a major societal disruption, the COVID-19 pandemic. Together, these findings illustrate the importance of geographic, cultural, and environmental context when defining healthy gut microbiota trajectories and contribute to a more inclusive, globally representative framework for understanding early-life microbiota development.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0010126"},"PeriodicalIF":5.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865938","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":"Novel insights into <i>Radix Pseudostellariae</i> saponins assist <i>Mycoplasma gallisepticum</i> attenuated vaccine to enhance the immunoprotection of chicken.","authors":"Qixian Feng, Lihua Liao, Yihua Gong, Jingru Xu, Xiangduan Wei, Zhengrun Xiao, Pengqiang Chen, Beilei Chen, Kaizhao Zhang, Quanxi Wang","doi":"10.1128/msystems.00781-26","DOIUrl":"https://doi.org/10.1128/msystems.00781-26","url":null,"abstract":"<p><p><i>Mycoplasma gallisepticum</i> (MG) is a major pathogen causing chronic respiratory disease in chickens, and the MG-attenuated vaccine (MGAV) often fails to induce effective mucosal immunity. <i>Radix Pseudostellariae</i> saponins (RPS), important bioactive components of the traditional Chinese herb, have been utilized for immunomodulation, although the underlying mechanisms remain to be elucidated. In this study, chickens were randomly assigned to groups receiving intranasal MGAV alone, MGAV plus RPS at different doses, or appropriate controls. Serum, tracheal mucosa, and respiratory lavage samples were collected for antibody measurement, cytokine profiling, histological assessment, and metagenomic/metabolomic analyses. RPS significantly increased MG-specific antibody levels and enhanced expression of the immunomodulatory cytokines, while suppressing that of pro-inflammatory factors. It also promoted tracheal mucosal integrity by elevating goblet cell numbers and mucosal epithelial height. Through metagenomic and metabolomic analysis, RPS was found to enrich the respiratory bacterium <i>Lactobacillus</i> sp. UMNPBX13, which was positively correlated with the metabolite phosphatidylcholine (PC). Intranasal administration of <i>Lactobacillus</i> increased mucin 2 (<i>MUC2</i>) and PC levels in tracheal mucosa. Similarly, PC combined with MGAV enhanced mucosal immunity by modulating cytokines and increasing MG-specific antibodies. These findings demonstrate that RPS enhances MGAV-induced respiratory mucosal immunity and provides a novel adjuvant strategy for improving poultry respiratory disease vaccines by modulating the respiratory microbiota, specifically through enrichment of <i>Lactobacillus</i> sp. UMNPBX13, which promotes PC production.IMPORTANCE<i>Mycoplasma gallisepticum</i> (MG) constitutes a notable challenge to poultry health. Although the MG-attenuated vaccine (MGAV) is widely used for disease control, it often fails to induce robust mucosal immunity. Here, we demonstrate that intranasal co-administration of <i>Radix Pseudostellariae</i> saponins (RPS) with MGAV augments mucosal immunoprotection. Integrated metagenomic and metabolomic analyses revealed that RPS enriches respiratory <i>Lactobacillus</i>, which in turn promotes the production of its key metabolite phosphatidylcholine (PC), thereby supporting mucosal immune enhancement. These findings offer a promising strategy for improving poultry vaccine efficacy and may provide a basis for future exploration of mucosal vaccination approaches in other animal species.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0078126"},"PeriodicalIF":5.2,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865935","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":"Longitudinal development of infant oral ecosystem: salivary metabolomic, bacteriome, and virome dynamics in early infancy.","authors":"Ting Li, Xingyi Lu, Nora Alomeir, Anthony Gaca, Michael Sohn, Steven Gill, Bradley Smith, Joshua Munger, Jin Xiao","doi":"10.1128/msystems.00946-26","DOIUrl":"10.1128/msystems.00946-26","url":null,"abstract":"<p><p>This prospective cohort study investigated the longitudinal development of the salivary bacteriome, virome, and metabolome during early infancy. We assessed the associations between oral bacteria, viruses, and metabolites from 10 mother-infant dyads, with oral samples collected at 1 and 2 years of age. Forty saliva and plaque samples underwent untargeted metabolomic analysis, and infant saliva samples underwent metagenomic sequencing. Maternal salivary and plaque metabolomic profiles remained largely stable, whereas infant profiles were clearly separated from maternal profiles and changed with age. Notably, infant dental plaque metabolism underwent more substantial changes from year 1 to year 2 than saliva, with age-dependent metabolite shifts mainly involving energy, amino acid, nucleotide, and lipid metabolic pathways. Our findings also revealed significant developmental shifts in salivary bacteriome, virome, and functional pathway profiles during early childhood. The most abundant oral bacteria in early life, comprising over 75% of total abundance, included <i>Veillonella, Streptococcus, Rothia, Prevotella, Neisseria</i>, and <i>Actinomyces species</i>. While human viruses like <i>Roseolovirus</i> were detected, bacteriophages constituted the majority of the virome. Comparing infants at year 1 and year 2, we identified differentially abundant bacteria, viruses, metabolic functional pathways, and specific metabolites. We observed associations between bacteria and viruses, noting that these cross-kingdom relationships attenuated as infants grew. The study results underscore the complex and dynamic development of the oral microbiome, virome, and metabolome during early childhood.IMPORTANCEThe human oral cavity undergoes substantial microbial and metabolic development during early childhood, yet the temporal changes in the infant oral ecosystem remain incompletely understood. In this study, we longitudinally profiled the salivary metabolome, bacteriome, and virome of infants at 1 and 2 years of age. We demonstrated that the infant oral metabolome undergoes substantial developmental shifts, particularly in pathways related to energy, amino acid, and lipid metabolism; whereas maternal metabolic profiles remained stable over the same period. Furthermore, our results revealed the dynamic assembly of infant salivary virome and bacteriome and their associations with the functional pathways and metabolites. These findings provide new insights into the complex and dynamic development of the oral microbiome, virome, and metabolome in early infancy.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0094626"},"PeriodicalIF":5.2,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865885","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":"Spatial constraints determine the spread of plasmid-encoded antibiotic resistance between bacterial colonies.","authors":"Josep Ramoneda, Deepthi P Vinod, Yinyin Ma, Chujin Ruan, Julian Schmidt, Michael Manhart, Daniel C Angst, David R Johnson","doi":"10.1128/msystems.00531-26","DOIUrl":"https://doi.org/10.1128/msystems.00531-26","url":null,"abstract":"<p><p>Plasmid transfer among bacteria is an important driver of the spread of antibiotic resistance. Surface-associated bacterial biomass is a hotspot for plasmid transfer due to the dense spatial packing of cells, but this biomass is often sparse (composed of discrete bacterial colonies). Compared to plasmid dynamics within a single colony, the determinants of plasmid transfer between discrete colonies are less understood. Yet, colonies routinely physically collide with each other as they grow and expand across surfaces. Here, we experimentally demonstrate that collisions between colonies of <i>Stutzerimonas stutzeri</i> and <i>Escherichia coli</i> enable the spread of an antibiotic resistance-encoding plasmid, with the extent of transfer determined by the spatial distance between bacterial inocula. To better understand how spatial constraints influence the mechanisms underlying inter-colony plasmid spread, we applied an individual-based model simulating plasmid dynamics between colliding colonies. Our simulations quantitatively predict how the probabilities of plasmid transfer and loss affect plasmid spread as colonies grow and collide. These effects are modulated by the distances between colonies and the spatial positioning of plasmid-carrying cells along the collision boundary. Our study reveals that inter-colony plasmid transfer is determined by the interplay between plasmid transfer, plasmid loss, and spatial constraints, expanding our understanding of plasmid dynamics in the spread of antibiotic resistance genes.IMPORTANCEThe spread of antibiotic resistance between spatially discrete microbial colonies is poorly understood, despite its relevance to persistent colonization on a variety of surfaces (e.g., medical devices, dental plaque, wound infections, indoor plumbing, etc.). Here, we combined experiments and individual-based modeling to show that physical collisions between growing colonies enable the spread of plasmids carrying antibiotic resistance genes. The extent of transfer depends on the initial spatial distance between colonies, the probabilities of plasmid transfer and loss, and the local spatial intermixing of plasmid-carrying and -free cells along the collision boundary. These findings reveal how the interplay between plasmid biology and microbial spatial organization governs the spread of antibiotic resistance and provide a quantitative framework for predicting plasmid dynamics in spatially structured environments.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":" ","pages":"e0053126"},"PeriodicalIF":5.2,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840855","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}