mSphere最新文献

{"title":"Antibiotic susceptibility of <i>Escherichia coli</i> is affected by evolutionary history but not by history of elemental limitation.","authors":"Marissa A Donofrio, Heather L Blasius, Catherine C Nguyen, Alexa L Schnell, Caroline B Turner","doi":"10.1128/msphere.00538-25","DOIUrl":"10.1128/msphere.00538-25","url":null,"abstract":"<p><p>Antibiotic resistance in bacteria is a global public health threat. To understand how the evolution of antibiotic susceptibility is affected by environmental conditions and prior evolutionary history, we worked with populations from the Long-Term Evolution Experiment (LTEE) with <i>Escherichia coli</i>. These populations previously evolved independently for 50,000 generations in an environment without antibiotics, making them an ideal system for studying the effect of evolutionary history on adaptation to new selective pressures. We further evolved five of the LTEE populations, as well as their shared ancestor, under either carbon- or nitrogen-limited conditions and then tested intrinsic resistance to four antibiotics. Evolution under elemental limitation did not have a significant impact on resistance to any of the tested antibiotics. However, some LTEE populations did have higher resistance than other populations. Susceptibility also varied within one population, which had the lowest level of resistance to all four antibiotics. We hypothesized that resistance levels might differ between two clades of bacteria that have coexisted within this population for more than 40,000 generations. Interestingly, although antibiotic susceptibility varied within the population, there was no consistent difference between clades. Instead, one particular clone isolated from the population exhibited higher resistance than the other clones sampled. These findings indicate that antibiotic resistance can vary both within and between experimentally evolved populations, even in the absence of direct selection on resistance. Our results also show that measured levels of susceptibility may depend on stochastic sampling effects during isolation of clones.IMPORTANCEAntibiotic resistance is one of the most pressing health challenges worldwide, and understanding how bacteria evolve resistance, even when not directly exposed to antibiotics, is critical for managing and predicting emerging threats. Our study leverages the unique Long-Term Evolution Experiment with <i>Escherichia coli</i> to show that both the evolutionary history of bacterial populations and random variation among individual clones can significantly influence intrinsic antibiotic susceptibility. Our results also suggest that elemental limitation, while a critical environmental variable, may not be an important driver of intrinsic antibiotic susceptibility, at least over short time frames.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0053825"},"PeriodicalIF":3.1,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13123722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499665","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":"CTG clade-specific proteins of the RSC chromatin-remodeling complex regulate cell cycle progression of a critical priority fungal pathogen, <i>Candida albicans</i>.","authors":"Ankita Joshi, Gayatri Brahmandam, Harini Kannan, Shilajit Roy, Sandhya Subramanian, Amartya Sanyal, Santanu Kumar Ghosh","doi":"10.1128/msphere.00084-26","DOIUrl":"10.1128/msphere.00084-26","url":null,"abstract":"<p><p>The remodels the structure of chromatin (RSC) and the homologous chromatin-remodeling complexes are known to regulate cell cycle progression in various organisms, including <i>Saccharomyces cerevisiae</i>, <i>Drosophila</i>, and <i>Homo sapiens</i>. In this work, we characterized the role of two novel CTG clade-specific proteins (Nri1 and Nri2) of the RSC complex in the regulation of cell cycle progression in a critical priority fungal pathogen, <i>Candida albicans</i>. We observed that Nri1, alone or along with Nri2, regulates cell cycle progression at multiple stages. The <i>nri1Δ/Δ</i> and <i>nri1Δ/Δ nri2Δ/Δ</i> mutants exhibited transient cell cycle arrest, defective spindle morphology, and cytokinesis. Transcriptomic analysis supported these mutant phenotypes and indicated a broad role of Nri proteins in the cell cycle. From our results, we conclude that Nri proteins are crucial for <i>C. albicans</i> proliferation and fitness.IMPORTANCEThe composition of the essential RSC chromatin-remodeling complex exhibits species-specific divergence, harboring unique subunits with distinct functions. In this study, we report that two fungal CTG clade-specific proteins of the <i>C. albicans</i> RSC complex, namely Nri1 and Nri2, can promote <i>C. albicans</i> fitness by regulating its cell cycle progression at multiple stages. Fitness defects, along with stressor sensitivity and differential expression of the genes regulating pathogenesis in the <i>nri</i> mutants, indicate the potential of the Nri proteins in the regulation of <i>C. albicans</i> virulence.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0008426"},"PeriodicalIF":3.1,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13123710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147574960","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":"A trypanosome trifecta: an independently tunable triple inducible system for genetic studies in <i>Trypanosoma brucei</i>.","authors":"Matt J Romprey, Raveen Armstrong, Peter McGill, Cara M Jenkins, Justin H Li, Michele M Klingbeil","doi":"10.1128/msphere.00596-25","DOIUrl":"10.1128/msphere.00596-25","url":null,"abstract":"<p><p><i>Trypanosoma brucei</i> is a model unicellular parasite for cellular and molecular genetic studies, but tools for more multiplexed experiments are limited. Tetracycline (Tet)-inducible gene regulation has been a long-standing and effective approach for overexpression, RNAi, and genome-wide screens and has been foundational for studying essential genes that are required for biological processes and identifying potential drug targets. To achieve greater flexibility in experimental design, we capitalized upon previously described dual inducer systems that combined vanillic acid (Van) or cumate (Cym) with Tet as inducers. Here, we report the development of a triple inducible system combining Cym, Van, and Tet repressors to selectively regulate the expression of three genes within a single cell line called PHITER. To demonstrate independent control, we adapted the previously characterized Van/Tet dual inducible RNAi complementation cell line, IBComp^VaT, for additional Cym inducible expression of an eGFP reporter. We provide evidence that each inducer operates independently with no evidence of leaky expression. In this system, Cym induction is specific and tunable. As proof of principle, we used triple induction for <i>POLIB</i> RNAi, complementation with a recoded ectopic POLIB-PTP variant, and overexpression of the maxicircle helicase. We confirmed that Cym inducible PIF2 overexpression resulted in massive overreplication of maxicircles that is suppressed when <i>POLIB</i> is silenced, thereby demonstrating a requirement for POLIB during replication stress. The triple inducible system enables the study of complex and pleiotropic phenotypes through a more sophisticated experimental design that could not previously be achieved and can be applied for the development of multiplexed genomic screens.IMPORTANCE<i>Trypanosoma brucei</i> is a protist parasite that causes significant health and economic burden for sub-Saharan Africa and serves as a key model organism for a group of eukaryotes called the kinetoplastids. <i>T. brucei</i> and related parasites contain an interlocked mtDNA network called kinetoplast DNA (kDNA), composed of maxicircles and minicircles. Although <i>T. brucei</i> is highly genetically tractable, limitations exist for more complex experimental designs and multiplexed forward genetic screens. Here, we describe the first triple inducible system in <i>T. brucei</i> or any eukaryote that combines three independent repressors (cumate [Cym], tetracycline [Tet], and vanillic acid [Van]) to selectively regulate three genes within a single cell line. We demonstrate the utility of the system using an eGFP reporter and robust RNAi complementation of kDNA polymerase POLIB. Furthermore, we investigate the role of POLIB in maxicircle replication by overexpressing the maxicircle helicase during <i>POLIB</i> RNAi, revealing an early requirement for POLIB during replication stress.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0059625"},"PeriodicalIF":3.1,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13123715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147512883","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":"Predicted and inducible prophages display contrasting virulence gene profiles within the prophage-SaPI mobilome of <i>Staphylococcus aureus</i>.","authors":"Alan Aguayo-González, Irma Martínez-Flores, Patricia Bustos, Rosa I Santamaría, Roberto Cabrera-Contreras, Areli Martínez-Gamboa, Rodrigo Ibarra-Chávez, Víctor González","doi":"10.1128/msphere.00103-26","DOIUrl":"10.1128/msphere.00103-26","url":null,"abstract":"<p><p>Prophages play a significant role in bacterial evolution by shaping genomic diversity, virulence, and host adaptation. This study investigated the prophage composition of 109 clinical <i>Staphylococcus aureus</i> isolates obtained from four tertiary care hospitals in Mexico City and compared these results with data from 993 global genomes. Prophages were present in 97% of local isolates. Consistently, analysis of the global genome collection revealed a 99% prevalence, supporting the near ubiquity of prophages in <i>S. aureus</i>. Analysis identified 216 genomic regions corresponding to the predicted prophages within the Mexican <i>S. aureus</i> isolates. A substantial fraction (19%) of the predicted prophages was identified as phage-inducible chromosomal islands (PICIs), such as SaPI1, SaPI2, and SaPIpt1028-like elements. These PICIs encoded anti-phage defense systems (63%) and virulence genes (27%). Experimental treatment with mitomycin C induced 17 temperate phages, of which 12 demonstrated functional activity and the ability to undergo lysogenic-lytic switching and reinfection. No virulence or antibiotic resistance genes were identified in these temperate phages. Conversely, several uninduced prophages coincided with the virulence determinants. These findings highlight the complexity of the <i>S. aureus</i> mobilome, characterized by distinct functional profiles and heterogeneous mobilization capabilities, which may influence the dissemination of virulence factors.IMPORTANCE<i>Staphylococcus aureus</i> is a significant hospital-associated pathogen whose evolutionary processes are shaped by mobile genetic elements, including prophages and phage-inducible chromosomal islands (PICIs). While computational analyses suggest that nearly all <i>S. aureus</i> genomes contain prophages, our findings indicate that only a subset is inducible following mitomycin C treatment. These temperate phages do not possess virulence genes; however, other predicted prophages are associated with virulence factors. Additionally, we identified numerous predicted prophages as PICIs, which harbored anti-phage defense mechanisms and toxins. This study highlights the intricate mobilome of <i>S. aureus</i> and the various strategies that contribute to its horizontal gene transfer and pathogenic evolution.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0010326"},"PeriodicalIF":3.1,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13123717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Pseudomonas aeruginosa lasR</i> mutants resist phagocytosis and alter inflammatory cytokine production by cystic fibrosis macrophages.","authors":"Daniel S Aridgides, Diane L Mellinger, Lorraine L Gwilt, Anthony R Correia, Carson E Finger, Jay Goddard, Thomas H Hampton, Dallas L Mould, Deborah A Hogan, Alix Ashare","doi":"10.1128/msphere.00702-25","DOIUrl":"10.1128/msphere.00702-25","url":null,"abstract":"<p><p>Cystic fibrosis (CF) is characterized by chronic muco-obstructive lung disease and infection. People with CF (pwCF) are often colonized with <i>Pseudomonas aeruginosa</i> for years to decades, allowing for evolutionary adaptation. In chronic <i>P. aeruginosa</i> lung isolates from pwCF, the quorum-sensing regulator LasR is frequently nonfunctional; however, the factors enabling <i>lasR</i> loss-of-function (LOF) mutant selection are incompletely understood. We hypothesized that LOF mutations in <i>lasR</i> could allow <i>P. aeruginosa</i> to resist the selective pressure of phagocytosis. We found that in multiple strain backgrounds, LasR LOF decreased phagocytosis by both model THP-1 and primary monocyte-derived macrophages, and <i>lasR</i> complementation increased phagocytosis in mutant strains. While exogenous administration of the quorum-sensing autoinducer 3-oxo-C12-homoserine-lactone, which is made by an enzyme regulated by LasR activity, inhibited phagocytosis and mitochondrial respiration, the phagocytosis resistance seen with <i>lasR</i> mutants appears to be bacterial cell intrinsic rather than due to secreted factors. Finally, we found that <i>lasR</i> LOF mutations altered the inflammatory profile upon infection of CF macrophages, with a shift from IL-1 family cytokine expression toward canonical inflammatory markers, including IL-6 and TNFα. Collectively, these data provide a potential explanation for both the prevalence of <i>lasR</i> mutants in the CF lung as well as their association with worse outcomes.IMPORTANCECystic fibrosis (CF) is a genetically inherited disease that leads to chronic lung infections. <i>Pseudomonas aeruginosa</i> is often implicated in the worsening of lung disease, and it evolves in the lung over time to resist eradication. One of the most commonly disrupted genes in <i>P. aeruginosa</i> isolates from chronically infected CF lungs is <i>lasR</i>, which encodes a transcription factor that regulates multiple virulence factors. What contributes to the apparent fitness of <i>lasR</i> mutants in the CF lung is not well known. Our study shows that <i>lasR</i> loss-of-function mutants resist phagocytosis by macrophages, one of the fundamental mechanisms of clearance by the immune system. We identify mechanisms promoting resistance to phagocytosis and explore the downstream consequences on inflammatory responses. Understanding why <i>lasR</i> mutations arise could inform strategies to eradicate them from the CF lung and improve outcomes.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0070225"},"PeriodicalIF":3.1,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13123724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147593393","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":"Carbon metabolism and niche adaptation in <i>Streptococcus pyogenes</i> pathogenesis.","authors":"Wei Xu, Cheryl Y M Okumura","doi":"10.1128/msphere.00668-25","DOIUrl":"10.1128/msphere.00668-25","url":null,"abstract":"<p><p>Responsible for over 500,000 deaths annually around the world, <i>Streptococcus pyogenes</i> (group A <i>Streptococcus</i> [GAS]) infections have resurged in the post-COVID-19 era due to immune debt and the rise of strains with enhanced adaptive capabilities. The formidable pathogenicity of GAS is fueled by metabolic plasticity that coordinates virulence with niche-specific adaptation. In this minireview, we dissect how GAS functions as a sophisticated metabolic decision-maker, revealing survival strategies of the bacteria that allow persistence and vulnerabilities that can be targeted for therapeutic development. From the oropharynx to the bloodstream, niche-specific carbon sources and availability dictate downstream biosynthetic processes, creating an integrated metabolic network that controls pathogen fitness. Dynamic shifts in central carbon metabolism are orchestrated by an expanded repertoire of global regulators that directly couple nutrient availability to virulence factor expression. The resulting bacterial metabolic byproducts serve as dual-purpose weapons, limiting competition with commensal microbes and reprogramming host cell immune responses. The ability of GAS to fine-tune and couple metabolism to niche-specific survival factors reveals pathogen-specific targets that can be exploited for therapy. We evaluate high-potential therapeutic strategies that aim to disrupt this critical metabolism-virulence nexus. The development of these precision anti-virulence strategies to counter GAS infections is critical in an era of rising antimicrobial resistance.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0066825"},"PeriodicalIF":3.1,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13123708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581727","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":"Enhancing immune protection in dairy cattle: role of <i>Escherichia coli</i> Nissle 1917 in boosting the efficacy of a <i>Mycoplasma bovis</i>-BoAHV-1 combined vaccine.","authors":"Sen Zhang, Guoxing Liu, Jianguo Chen, Aizhen Guo, Yingyu Chen","doi":"10.1128/msphere.00178-26","DOIUrl":"https://doi.org/10.1128/msphere.00178-26","url":null,"abstract":"<p><p>Bovine respiratory disease (BRD) ranks among the most prevalent and economically burdensome diseases affecting the global dairy cattle industry, primarily resulting from co-infection with multiple pathogens, including <i>Mycoplasma bovis</i> (<i>M. bovis</i>) and bovine alphaherpesvirus type 1 (BoAHV-1). Despite the availability of vaccines, promoting their immunogenicity to deliver rapid, effective protection remains a critical challenge. The non-pathogenic probiotic <i>Escherichia coli</i> Nissle 1917 (EcN) has exhibited immunomodulatory properties related to digestive health; however, its potential as an adjuvant in bovine respiratory applications remains unexplored. In this study, we investigated the role of EcN as an immune enhancer in dairy calves for the first time, emphasizing its effects on both innate and adaptive immune responses when administered alongside an <i>M. bovis</i>-BoAHV-1 vaccine. Our findings revealed that all calves maintained normal clinical signs following EcN administration. Compared to the blank control, EcN treatment significantly upregulated natural immune markers. Furthermore, the combination of EcN with the <i>M. bovis</i>-BoAHV-1 vaccine elicited superior adaptive responses, evident in the boosted intensity and duration of both cellular and humoral immunity. Under experimental challenge conditions, the EcN-treated vaccinated group showed a more robust specific immune response, along with lower pathogen shedding titers and shorter duration compared to calves receiving the combined vaccine alone. In conclusion, EcN can safely and effectively activate the innate immune response of dairy calves, improving the adaptive immune response induced by a combined vaccine. Our findings represent the first confirmation of EcN's applicability in BRD and offer a novel strategy for enhancing vaccine protective efficacy.IMPORTANCEBovine respiratory disease is a major cause of economic losses in the global cattle industry, partly because of the delayed efficacy of current vaccines. This study investigated the intranasal administration of the probiotic <i>Escherichia coli</i> Nissle 1917 to enhance bovine immunity. The results illustrated that this probiotic safely activated the innate immune system, bridging the gap in protection between vaccination and the development of specific immune responses. When paired with a combined vaccine targeting <i>Mycoplasma bovis</i> and bovine alphaherpesvirus type 1, the probiotic significantly elevated protective antibody levels and reduced pathogen shedding and duration. These findings introduce an innovative non-antibiotic strategy for enhancing respiratory health in the cattle industry, providing a valuable tool to improve disease resistance and potentially reduce reliance on antimicrobial drugs.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0017826"},"PeriodicalIF":3.1,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777001","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":"Diversity and geographical distribution of potential carbon monoxide oxidizers using molybdenum-containing enzymes in the ocean.","authors":"Yoshinari Imaura, Keigo Yamamoto, Ryoma Kamikawa, Takashi Yoshida","doi":"10.1128/msphere.00062-26","DOIUrl":"https://doi.org/10.1128/msphere.00062-26","url":null,"abstract":"<p><p>Carbon monoxide (CO) evolves from photochemical or thermal reactions in the ocean. It is estimated that 90% of oceanic CO is consumed by CO-oxidizing prokaryotes, which convert CO to carbon dioxide using molybdenum-containing CO dehydrogenase (Mo-CODH). Investigation of form I <i>cox</i>, which encodes Mo-CODH, has revealed that oceanic prokaryotes with form I <i>cox</i> (potential <i>cox</i>-containing CO oxidizers: p<i>cox</i>-CO oxidizers) belong to eight phyla and occupy 10%-20% of prokaryotes. However, previous studies may have overestimated their diversity due to the use of less stringent criteria, and their ecology remains poorly understood. In this study, we characterized p<i>cox</i>-CO oxidizers by identifying form I <i>cox</i> from prokaryotic genomes reconstructed from the ocean. We used criteria that considered the phylogeny of Cox, their active site motifs, and the operon structure of <i>cox</i>. As a result, 233 species from nine phyla, which included 207 species unknown to be p<i>cox</i>-CO oxidizers, were found. We investigated the biogeography of each species and found 34 species that dominate in particular oceanic regions. Among the 34 species, 11 co-occurred with either of 20 prokaryotic species, and the co-occurring partners varied among species. No functional genes except those related to CO oxidation were shared between the 11 species, which implied the absence of common molecular basis that underlies ecological interaction between p<i>cox</i>-CO oxidizers and other prokaryotes. Finally, we performed absolute quantification of four species of p<i>cox</i>-CO oxidizers that were predicted to be dominant in Osaka Bay, Japan. It showed that p<i>cox</i>-CO oxidizers occupied over 8.49% of the bacterial community.IMPORTANCEThe ocean is a source of carbon monoxide (CO), an indirect greenhouse gas that supports the accumulation of methane and the production of a precursor of tropospheric ozone. The primary sink of CO in the ocean is prokaryotic CO oxidizers which possess molybdenum-containing CO dehydrogenase (Mo-CODH). Understanding CO flux therefore requires ecological characterization of prokaryotes carrying <i>cox,</i> which encode Mo-CODH. We provide a comprehensive, well-curated catalog of such prokaryotes (potential <i>cox</i>-containing CO oxidizers: p<i>cox</i>-CO oxidizers) in the ocean that not only revealed their diversity but also enabled species-specific ecological assessments. Co-occurrence analyses and genomic analysis of p<i>cox</i>-CO oxidizers uncovered substantial variation in their co-occurring prokaryotic partners and functional gene repertoires. The lack of shared co-occurrence and conserved genes suggests that CO oxidation via Mo-CODH does not mediate ecological interactions. These findings provide a foundation for future studies of p<i>cox</i>-CO oxidizers and offer new insight into ecological roles of CO oxidizers.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0006226"},"PeriodicalIF":3.1,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776954","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":"mSphere of Influence: Host-pathogen interactions-the fascinating world of molecular interplay.","authors":"Dilip Kumar","doi":"10.1128/msphere.00907-25","DOIUrl":"https://doi.org/10.1128/msphere.00907-25","url":null,"abstract":"<p><p>Dilip Kumar is a structural biologist, working on developing novel antiviral strategies against pathogenic RNA viruses by using an integrated structural biology approach. In this mSphere of Influence article, he emphasizes how two remarkable research articles on host-pathogen interactions, \"Inhibition of IRGM establishes a robust antiviral immune state to restrict pathogenic viruses\" by P. Nath, N. R. Chauhan, K. K. Jena, A. Datey, et al. (EMBO Rep 22:EMBR202152948, 2021, https://doi.org/10.15252/embr.202152948), and \"Cotranslational prolyl hydroxylation is essential for flavivirus biogenesis\" by R. Aviner, K. H. Li, J. Frydman, and R. Andino (Nature, 596:558-564, 2021, https://doi.org/10.1038/s41586-021-03851-2), sparked his interest in pursuing host-pathogen interactions to develop a broad range of antiviral therapeutics.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0090725"},"PeriodicalIF":3.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777013","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":"Pan-genomic insights into resistance, virulence, and stress adaptation in <i>Clostridium perfringens</i> from the Tibetan Plateau.","authors":"Runbo Luo, Yanxi Wan, Wanting Chen, Hongyun Wei, Junyang Wang, Zhanchun Bai, Kexin Li, Yanan Zhong, Bin Ma, Hui Jin, Sizhu Suolang","doi":"10.1128/msphere.00792-25","DOIUrl":"10.1128/msphere.00792-25","url":null,"abstract":"<p><p><i>Clostridium perfringens</i> is a ubiquitous foodborne and zoonotic pathogen responsible for necrotizing enteritis, food poisoning, and gas gangrene in humans and livestock, with mortality reaching 100% in specific subtypes. The Qinghai-Tibetan Plateau, with its high altitude, hypoxia, large temperature fluctuations, and strong UV radiation, imposes a strong selective regime that drives distinctive, plateau-specific microbial evolution. We isolated and sequenced eight <i>C. perfringens</i> isolates from yaks and Tibetan pigs and analyzed them with 129 public genomes. Multilocus sequence typing (MLST) revealed extensive genetic heterogeneity, with 35 novel alleles and 18 novel sequence types (STs), all plateau isolates carrying novel alleles or STs. Toxinotyping identified six toxinotypes, dominated by A (43.0%) and F (42.3%), with virulence gene repertoires matching toxinotype assignments. Sixteen antimicrobial resistance (AMR) genes across eight drug classes were detected, with vancomycin- and defensin-like genes present in >96.0% of isolates; four were linked to mobile genetic elements (MGEs) or type IV secretion systems (T4SS). Environmental tolerance assays showed that three plateau isolates maintained growth at pH 7.5 under anaerobic conditions, while the growth of all isolates was inhibited at pH 7.0. Pan-genomic association analysis identified a 146-node, 3,390-edge network, with <i>IS</i> family transposases (<i>ISCbt3/ISCpe4</i>), sigma factors (<i>sigL</i> and <i>sigA</i>), and DNA polymerase I (<i>polA</i>) as central hubs potentially mediating stress adaptation. Genomic epidemiology of <i>C. perfringens</i> from the Tibetan Plateau reveals marked genetic diversity, broad resistance, toxinotype-defined virulence, and genetic signatures of high-altitude adaptation, underpinning evidence-based control in plateau ecosystems.IMPORTANCE<i>Clostridium perfringens</i> is a widespread pathogen, but its adaptation to extreme environments like high-altitude plateaus remains a mystery. Our integrated genomic analysis of 137 strains, including 8 newly sequenced from the plateau, uncovers a startling reality: this region harbors a highly diverse population with near-universal resistance to critical antibiotics. We identified new sequence types (STs) and genetic \"hubs\" that may drive this adaptation. These findings have profound implications for One Health as they highlight an environmental niche where resistance can evolve and potentially spread, underscoring the urgent need for surveillance in unique ecosystems.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0079225"},"PeriodicalIF":3.1,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723286","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}