mSphere最新文献

{"title":"Modulatory impact of <i>Bifidobacterium longum</i> subsp. <i>longum</i> BL21 on the gut-brain-ovary axis in polycystic ovary syndrome: insights into metabolic regulation, inflammation mitigation, and neuroprotection.","authors":"Yao Dong, Shengnan Yang, Shu Zhang, Yuan Zhao, Xinlan Li, Mei Han, Zhonghui Gai, Kang Zou","doi":"10.1128/msphere.00887-24","DOIUrl":"10.1128/msphere.00887-24","url":null,"abstract":"<p><p>This study evaluates the efficacy of <i>Bifidobacterium longum</i> subsp. <i>longum</i> BL21 in mitigating symptoms of polycystic ovarian syndrome (PCOS) in DHT-induced PCOS model mice. It focuses on BL21's role in modulating metabolic dysregulation, inflammation, and neuroprotection via the gut-brain-ovary axis. Employing an 8-week treatment regimen, this research assessed the effects of BL21 on prenatal androgen-induced PCOS in ICR mice. Evaluations included body weight, glucose tolerance tests, serum analyses of BDNF, inflammatory markers, sex hormone levels, and 16S rRNA gene sequencing for gut microbiota diversity and composition. Twenty-four ICR mice with induced PCOS served as subjects to examine the probiotic's impact. Mice were administered a daily oral dose of 1 × 10⁹ CFU of BL21 continuously for a total of 8 weeks. BL21 significantly enhanced sex hormone levels (<i>P</i> < 0.05), particularly those of follicle-stimulating hormone (FSH) and estradiol (E2), indicating improved ovarian function and offering a novel PCOS treatment approach. The intervention notably curbed weight gain and improved glucose tolerance in PCOS mice (<i>P</i> < 0.05). BL21 reduced inflammatory markers such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and lipopolysaccharides (LPS), while increasing IL-10, BDNF, FSH, and E2 levels (<i>P</i> < 0.05 for all). It also enriched gut microbiota diversity, enhancing populations of <i>Bifidobacterium</i> and <i>Lactobacillus</i>. Correlation analyses underscored the positive shifts in microbiota linked to beneficial hormonal and inflammatory profiles. BL21 shows promise in alleviating PCOS symptoms through metabolic regulation, inflammation reduction, and neuroprotection, validating its potential in integrated therapeutic strategies.IMPORTANCEPolycystic ovarian syndrome (PCOS) is a prevalent endocrine disorder affecting women of reproductive age, characterized by metabolic irregularities, hormonal imbalances, and chronic inflammation. Existing treatments are often inadequate, addressing symptoms without targeting the underlying etiological factors. The investigation of <i>Bifidobacterium longum</i> subsp. <i>longum</i> BL21 as a probiotic intervention offers a novel approach by potentially regulating the gut-brain-ovary axis. This could lead to innovative therapeutic strategies that not only manage but also potentially reverse the multifaceted symptoms of PCOS, enhancing quality of life and reproductive health.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0088724"},"PeriodicalIF":3.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080722","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":"BALF editome profiling reveals A-to-I RNA editing associated with severity and complications of <i>Mycoplasma pneumoniae</i> pneumonia in children.","authors":"Yun-Yun Jin, Yun Guo, Su-Wan Xiong, Na Zhang, Jian-Huan Chen, Feng Liu","doi":"10.1128/msphere.01012-24","DOIUrl":"https://doi.org/10.1128/msphere.01012-24","url":null,"abstract":"<p><p><i>Mycoplasma pneumoniae</i> is an important human respiratory pathogen that causes mild-to-moderate community-acquired <i>M. pneumoniae</i> pneumonia (MPP), particularly in children. RNA editing plays a vital role in pathogen infection and host immune response, but it remains largely unknown how it could be involved in the epigenetic regulation of host response to <i>M. pneumoniae</i> infection. In the present study, we performed an epitranscriptomic analysis of adenosine to inosine (A-to-I) editing in 39 bronchoalveolar lavage fluid (BALF) samples from the severe side (SS) and the opposite side (OS) of patients with MPP. Our editome profiling identified 87 differential RNA editing (DRE) events in 50 genes, especially missense editing events that recoded C-C motif chemokine receptor-like 2 (<i>CCRL2</i>, p.K147R) and cyclin I (<i>CCNI</i>, p.R75G). The expression of adenosine deaminase acting on RNA (<i>ADAR</i>) significantly increased on SS compared to OS and positively correlated with the average RNA editing level and individual DRE events. Meanwhile, functional enrichment analysis showed that DRE was observed in genes primarily associated with the negative regulation of innate immune response, type I interferon production, and cytokine production. Further comparison of SS between complicated MPP (CMPP) and non-complicated MPP (NCMPP) revealed RNA editing events associated with MPP complications, with a higher <i>ADAR</i> expression in CMPP than NCMPP. By identifying DRE events as biomarkers associated with MPP severity and complications, our editome profiling provides new insight into the potential role played by A-to-I RNA editing in modulating the host's immune system during <i>M. pneumoniae</i> infection.IMPORTANCEOur research investigates how <i>Mycoplasma pneumoniae</i>, a common respiratory pathogen, influences how our cells modify their genetic instructions. By studying RNA editing changes in bronchoalveolar lavage fluid from patients with <i>M. pneumoniae</i> pneumonia, we aim to investigate how <i>M. pneumoniae</i> infection alters epigenetics and contributes to the disease severity and complications. Understanding such epigenetic alterations not only sheds light on the mechanisms underlying <i>M. pneumoniae</i> infection but also holds potential implications for developing better diagnostic tools and therapies. Ultimately, this work may facilitate the design of more targeted treatments to alleviate the impact of respiratory infections caused by the pathogen. Our findings may also offer broader insights into how microbial infections reshape immune processes, highlighting the importance of RNA editing in host-pathogen interactions.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0101224"},"PeriodicalIF":3.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492973","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":"Exploring the differential localization of protein kinase A isoforms in <i>Candida albicans</i>.","authors":"Saif Hossain, Zhongle Liu, Nicole Robbins, Leah E Cowen","doi":"10.1128/msphere.01037-24","DOIUrl":"https://doi.org/10.1128/msphere.01037-24","url":null,"abstract":"<p><p>The cAMP-dependent protein kinase A (PKA) plays important roles in a wide range of biological processes in eukaryotic organisms. In the fungal pathogen <i>Candida albicans</i>, PKA is a critical regulator of morphological transitions, which are a key virulence trait. PKA is composed of two catalytic isoforms, Tpk1 and Tpk2, which are often thought to act together in a complex with the regulatory subunit Bcy1. Although Tpk1 and Tpk2 have some redundant functions, they also have distinct cellular functions for which the mechanistic underpinnings remain largely elusive. Here, we constructed functional GFP-tagged fusion proteins for Tpk1, Tpk2, and Bcy1 to explore the localization of PKA isoforms. We observed that the PKA holoenzyme is mainly found in the cytoplasm, as Bcy1 is always excluded from the nucleus. Under glucose-replete conditions, both Tpk1 and Tpk2 translocate into the nucleus from the cytosol. In the presence of glycerol, Tpk1 resides in the cytosol, whereas Tpk2 and Bcy1 become enriched on the vacuolar membrane. As the C-terminal domains of Tpk are highly homologous, we investigated the localization and function of hybrid Tpk proteins with exchanged N-terminal domains. We found the catalytic C-terminus of Tpk1 is required for morphogenesis in solid medium, whereas the C-terminus of Tpk2 is critical for filamentation in liquid. Interestingly, the N-terminus of Tpk2 drives its localization to the vacuolar membrane. Our work highlights environmentally contingent localization patterns for the PKA subunits and suggests that the nuclear localization of Tpk is not sufficient to induce the filamentation program in a leading fungal pathogen of humans.IMPORTANCEFungal pathogens have a devastating impact on human health worldwide. They infect billions of people and kill more than 2.5 million per year. <i>Candida albicans</i> is a leading human fungal pathogen responsible for causing life-threatening systemic disease in immunocompromised individuals. A key virulence trait in <i>C. albicans</i> is the ability to switch between yeast and filamentous forms. The conserved protein kinase A (PKA) regulates diverse functions in the cell, including growth and filamentation. Although PKA has been studied in <i>C. albicans</i> for decades, the subcellular localization of PKA has not been thoroughly investigated. Here, we constructed functional GFP-tagged PKA subunits to explore their localization. We identified differential localization patterns for the PKA subunits that are carbon-source dependent and report that these proteins localize into foci in response to diverse environmental stresses. These findings further our understanding of a critical regulator of growth and virulence in <i>C. albicans</i>.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0103724"},"PeriodicalIF":3.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The circulating plasma microRNA signature in human visceral leishmaniasis.","authors":"Ritirupa Roy, Cinthia L Hudachek, Shashi Bhushan Chauhan, Shashi Kumar, Awnish Kumar, Bayan Zhanbolat, Madhukar Rai, Rajiv Kumar, Shyam Sundar, Mary E Wilson","doi":"10.1128/msphere.00646-24","DOIUrl":"10.1128/msphere.00646-24","url":null,"abstract":"<p><p>Visceral leishmaniasis (VL) is a vector-borne disease caused by the obligate intracellular protozoan <i>Leishmania donovani</i> in India. VL can be complicated by post-kala-azar dermal leishmaniasis (PKDL), a macular or nodular rash that develops in 10%-20% of patients after treatment of VL in India. Patients with PKDL are infectious to sand flies, promoting further transmission of the parasite. MicroRNAs (miRNAs) are 18-25 nt, non-coding RNAs that simultaneously regulate the expression of several or many target transcripts. This study was based on the hypothesis that the host response to <i>L. donovani</i> is modified by distinct sets of miRNAs in VL or PKDL and that these might differ from healthy controls. We investigated this hypothesis using a NanoString panel to profile the miRNAs expressed in the plasma of patients with VL or PKDL diagnosed at a hospital in Bihar, India. We compared these to plasma microRNAs of healthy control individuals from the same endemic villages. miRNAs <i>hsa-miR-223-3p, hsa-miR-191-5p, hsa-miR-23a-3p,</i> and <i>hsa-1285-5p</i> were significantly higher in the plasma samples from patients with VL compared to either PKDL or endemic controls. Prediction programs highlighted potential mRNA targeted by these miRNAs, among which we verified the down-modulation of several transcripts belonging to the NFκB and NLRP3 inflammasome pathways in circulating leukocytes of VL patients. By contrast, miRNA patterns in subjects with PKDL were similar to control subjects, possibly suggesting that the pathogenic immune response during PKDL is primarily localized in the skin.IMPORTANCEInfection of humans with the protozoan <i>Leishmania donovani</i> can be asymptomatic or it can cause fatal visceral leishmaniasis (VL), sometimes followed by the cutaneous complication PKDL. Parasites are spread through sand fly bites in endemic regions, and parasites in post-kala-azar dermal leishmaniasis (PKDL) skin lesions are a source of prolonged parasite transmission to sand flies, compromising disease eradication efforts. Since microRNAs can simultaneously modify the expression of multiple genes, we examined microRNAs in the blood that might be partial determinants of pathogenic responses leading to VL or PKDL. Our studies revealed several miRNAs expressed that are elevated in the plasma of patients with VL, which suppress some of the inflammatory responses that promote parasite killing. However, miRNA profiles were very similar between PKDL patients and controls, raising the possibility that major factors that lead to prolonged retention of parasites in the skin during PKDL are not systemic but are localized in the skin.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0064624"},"PeriodicalIF":3.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053023","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: Lighting up organellar communication in protozoan parasites.","authors":"Diego Huet","doi":"10.1128/msphere.00574-24","DOIUrl":"10.1128/msphere.00574-24","url":null,"abstract":"<p><p>Diego Huet works in molecular parasitology, focusing on the organellar biology of <i>Toxoplasma gondii</i>. In this mSphere of Influence article, he reflects on how the article \"Efficient proximity labeling in living cells and organisms with turboID\" (Branon et al., 2018) impacted his research and the strategies used to dissect inter-organellar interactions in <i>T. gondii</i>.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0057424"},"PeriodicalIF":3.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255999","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":"Inhibition of Unc-51-like-kinase is mitoprotective during <i>Pseudomonas aeruginosa</i> infection in corneal epithelial cells.","authors":"Rajalakshmy Ayilam Ramachandran, Rossella Titone, Joelle T Abdallah, Mahad Rehman, Mou Cao, Hamid Baniasadi, Danielle M Robertson","doi":"10.1128/msphere.00537-24","DOIUrl":"10.1128/msphere.00537-24","url":null,"abstract":"<p><p><i>Pseudomonas aeruginosa</i> (PA) is an opportunistic gram-negative pathogen that can infect the cornea, leading to permanent vision loss. Autophagy is a cannibalistic process that drives cytoplasmic components to the lysosome for degradation and/or recycling. Autophagy has been shown to play a key role in the removal of intracellular pathogens and, as such, is an important component of the innate immune response. Autophagy is intimately linked to mitochondria, organelles that mediate energy homeostasis, immune signaling, and cell death. Using a combination of biochemical and imaging approaches, we investigated the effects of PA on autophagy and host cell mitochondria in relation to pro-inflammatory cytokine expression. Using a standard invasive test strain of PA, we show that PA infection triggers dephosphorylation of the mechanistic target of rapamycin in corneal epithelial cells, leading to the induction of autophagy through ULK1/2. This was associated with robust mitochondrial depolarization, changes in mitochondrial ultrastructure, and an increase in IL-6 and IL-8 secretion. PA infection was also associated with an increase in purine metabolism by host cells. Treatment with the ULK1/2 inhibitor, MRT68921, which blocks phagophore formation, attenuated levels of intracellular PA in corneal epithelial cells. Unexpectedly, treatment of cells with MRT68921 blocked PA-induced mitochondrial depolarization and downregulated purine and pyrimidine metabolism. While MRT68921 attenuated the PA-induced increase in IL-6, it further increased IL-8 and neutrophil chemotaxis. This was associated with the nuclear internalization of NF_κB. Taken together, these findings highlight a novel mechanism whereby the inhibition of ULK1/2 activity confers mitoprotection during PA infection in corneal epithelial cells.IMPORTANCE<i>Pseudomonas aeruginosa</i> (PA) is a common pathogen that can cause severe disease in man. In the eye, PA infection can lead to blindness. In this study, we show that PA induces autophagy, a mechanism whereby cells recycle damaged proteins and organelles. PA infection further depolarizes mitochondria, leading to the release of pro-inflammatory mediators. Unexpectedly, the inhibition of ULK1/2, an enzyme involved in the early stages of autophagy, not only inhibits autophagy but enhances mitochondrial polarization. This leads to a reduction in intracellular levels of PA and changes in the inflammatory milieu. Together, these data suggest that the inhibition of ULK1/2 may be mitoprotective in corneal epithelial cells during PA infection.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0053724"},"PeriodicalIF":3.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952311","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":"Overexpression of the RNA-binding protein NrdA affects global gene expression and secondary metabolism in <i>Aspergillus</i> species.","authors":"Chihiro Kadooka, Kosuke Izumitsu, Teigo Asai, Kentaro Hiramatsu, Kazuki Mori, Kayu Okutsu, Yumiko Yoshizaki, Kazunori Takamine, Masatoshi Goto, Hisanori Tamaki, Taiki Futagami","doi":"10.1128/msphere.00849-24","DOIUrl":"10.1128/msphere.00849-24","url":null,"abstract":"<p><p>RNA-binding protein Nrd1 plays a role in RNA polymerase II transcription termination. In this study, we showed that the orthologous NrdA is important in global mRNA expression and secondary metabolism in <i>Aspergillus</i> species. We constructed an <i>nrdA</i> conditional expression strain using the Tet-On system in <i>Aspergillus luchuenesis</i> mut. <i>kawachii</i>. Downregulation of <i>nrdA</i> caused a severe growth defect, indicating that NrdA is essential for the proliferation of <i>A. kawachii</i>. Parallel RNA-sequencing and RNA immunoprecipitation-sequencing analysis identified potential NrdA-interacting transcripts, corresponding to 32% of the predicted protein-coding genes of <i>A. kawachii</i>. Subsequent gene ontology analysis suggested that overexpression of NrdA affects the production of secondary metabolites. To clarify this, we constructed <i>Aspergillus nidulans</i>, <i>Aspergillus fumigatus</i>, and <i>Aspergillus oryzae</i> strains overexpressing NrdA in the early developmental stage. Overexpression of NrdA reduced the production of sterigmatocystin and penicillin in <i>A. nidulans</i>, as well as that of helvolic acid and pyripyropene A in <i>A. fumigatus</i>. Moreover, it increased the production of kojic acid and reduced the production of penicillin in <i>A. oryzae</i>. These effects were accompanied by almost consistent changes in the mRNA levels of relevant genes. Collectively, these results suggest that NrdA is the essential RNA-binding protein, which plays a significant role in global gene expression and secondary metabolism in <i>Aspergillus</i> species.IMPORTANCENrd1, a component of the Nrd1-Nab3-Sen1 complex, is an essential RNA-binding protein involved in transcriptional termination in yeast. However, its role in filamentous fungi has not been studied. In this study, we characterized an orthologous NrdA in the <i>Aspergillus</i> species, identified potential NrdA-interacting mRNA, and investigated the effect of overexpression of NrdA on mRNA expression in <i>Aspergillus luchuensis</i> mut. <i>kawachii</i>. The results indicated that NrdA controls global gene expression involved in versatile metabolic pathways, including the secondary metabolic process, at least in the early developmental stage. We demonstrated that NrdA overexpression significantly affected the production of secondary metabolites in <i>Aspergillus nidulans</i>, <i>Aspergillus oryzae</i>, and <i>Aspergillus fumigatus</i>. Our findings are of importance to the fungal research community because the secondary metabolism is an industrially and clinically important aspect for the <i>Aspergillus</i> species.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0084924"},"PeriodicalIF":3.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033755","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: Seeking the unseen fungi in tumors.","authors":"Ning-Ning Liu","doi":"10.1128/msphere.00988-24","DOIUrl":"10.1128/msphere.00988-24","url":null,"abstract":"<p><p>Ningning Liu works in the field of fungal infection and cancer progression, with a particular focus on the mechanism of host-pathogen interaction. In this mSphere of influence article, he reflects on how papers entitled \"The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL,\" by B. Aykut, S. Pushalkar, R. Chen, Q. Li, et al. (Nature 574:264-267, 2019, https://doi.org/10.1038/s41586-019-1608-2), and \"A pan-cancer mycobiome analysis reveals fungal involvement in gastrointestinal and lung tumors,\" by A. B. Dohlman, J. Klug, M. Mesko, I. H. Gao, et al. (Cell 185:3807-3822.E12, 2022, https://doi.org/10.1016/j.cell.2022.09.015), emphasized the non-negligible role of fungi in the host and demonstrated a connection between fungi and cancer. These researches arouse his interest in seeking the novel fungal pathogen lurking inside tumors and understanding the unexplored mechanisms behind the severe fungal infections in cancer patients.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0098824"},"PeriodicalIF":3.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053020","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":"Correction for Gier et al., \"Analysis of Yeast Killer Toxin K1 Precursor Processing via Site-Directed Mutagenesis: Implications for Toxicity and Immunity\".","authors":"Stefanie Gier, Manfred J Schmitt, Frank Breinig","doi":"10.1128/msphere.01066-24","DOIUrl":"10.1128/msphere.01066-24","url":null,"abstract":"","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0106624"},"PeriodicalIF":3.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059859","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":"Detection of chronic wasting disease prions in the farm soil of the Republic of Korea.","authors":"Kyung-Je Park, Hoo-Chang Park, Yu-Ran Lee, Gordon Mitchell, Young Pyo Choi, Hyun-Joo Sohn","doi":"10.1128/msphere.00866-24","DOIUrl":"10.1128/msphere.00866-24","url":null,"abstract":"<p><p>Chronic wasting disease (CWD) is a highly contagious prion disease occurring in free-ranging and farmed cervids. CWD continues to spread uncontrolled across North America, and cases continue to be detected almost every year in the Republic of Korea. CWD-infected animals contaminate the soil by releasing infectious prions through their excreta, and shed prions accumulate and remain infectious in the soil for years. Given that the upper soil levels can become contaminated with prions and serve as infectivity reservoirs facilitating horizontal transmission of CWD, the ability to detect prions in the soil is needed for monitoring and managing CWD spread. Using the protein misfolding cyclic amplification (PMCA) technique, we investigated whether prions could be amplified and detected in farm soil experimentally exposed to CWD-infected brain homogenate as well as in the soil of CWD-affected farms. From each soil sample, we performed 10 serial extractions and used these 10 extracts as PMCA templates. Here, we show that prion seeding activity was detected in extracts from farm soil following 4 years of incubation with CWD-infected brain homogenate. More importantly, 13 of 38 soil samples collected from six CWD-affected farms displayed prion seeding activity, with at least one soil sample in each farm being PMCA positive. Mouse bioassays confirmed the presence of prion infectivity in the soil extracts in which PMCA seeding activity was detected. This is the first report describing the successful detection of prions in soil collected from CWD-affected farms, suggesting that PMCA conducted on serial soil extracts is a sensitive means for prion detection in CWD-contaminated soil.IMPORTANCEChronic wasting disease (CWD) is a highly contagious prion disease affecting free-ranging and farmed cervids. CWD continues to spread uncontrollably across North America, and multiple cases are detected annually in the Republic of Korea. Prions shed from CWD-infected animals remain infectious in the soil for years, serving as infectivity reservoirs that facilitate horizontal transmission of the disease. Therefore, the ability to detect CWD prions in soil is crucial for monitoring and managing the spread of the disease. In this study, we have demonstrated for the first time that prions in the soil of CWD-affected farms can be reliably detected using a combination of serial soil extraction and a prion amplification technique. Our data, in which at least one soil sample tested positive for CWD in each of the six CWD-affected farms analyzed, suggest that the approach employed in this study is a sensitive method for prion detection in CWD-contaminated soil.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0086624"},"PeriodicalIF":3.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066868","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}