mSphere最新文献

{"title":"mSphere of Influence: <i>Toxoplasma gondii</i> tissue cysts-who are you calling dormant?","authors":"Robyn S Kent","doi":"10.1128/msphere.00028-25","DOIUrl":"https://doi.org/10.1128/msphere.00028-25","url":null,"abstract":"<p><p>Robyn Kent studies how <i>Toxoplasma gondii</i> chronic infections can persist in different tissues in the host and how latency is controlled to enable maintenance, transmission, and reactivation of the parasite. In this mSphere of Influence article, she reflects on how two papers from the laboratories of Dr. A. P. Sinai and Dr. L. D. Sibley have impacted her thinking on the chronic stage of <i>T. gondii</i> infections.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0002825"},"PeriodicalIF":3.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605932","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 Gcn5 lysine acetyltransferase mediates cell wall remodeling, antifungal drug resistance, and virulence of <i>Candida auris</i>.","authors":"Manju Chauhan, Raju Shivarathri, Ariel A Aptekmann, Anuradha Chowdhary, Karl Kuchler, Jigar V Desai, Neeraj Chauhan","doi":"10.1128/msphere.00069-25","DOIUrl":"https://doi.org/10.1128/msphere.00069-25","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;i&gt;Candida auris&lt;/i&gt; has emerged as a multidrug-resistant human fungal pathogen that causes infections of high morbidity and mortality. However, the molecular mechanisms underlying pronounced multidrug resistance and host-pathogen interactions are poorly understood. Here, we show that &lt;i&gt;C. auris GCN5&lt;/i&gt; lysine acetyltransferase is essential for cell wall remodeling, antifungal drug resistance, and virulence. The &lt;i&gt;Candida albicans GCN5&lt;/i&gt; has previously been shown to be an important regulator of antifungal drug resistance and virulence. Therefore, to identify Gcn5-dependent evolutionary conserved as well as divergent transcriptional networks between the two species, we performed comparative transcriptional analysis. The gene set enrichment analysis of &lt;i&gt;C. auris&lt;/i&gt; vs &lt;i&gt;C. albicans gcn5&lt;/i&gt;Δ transcriptomic data revealed several major biological pathways and processes including sphingolipid metabolism and glycosylphosphatidylinositol anchor biosynthesis to be enriched in both species. Consistent with these data, we found a prominent role for &lt;i&gt;C. auris&lt;/i&gt; Gcn5 in maintaining cell-wall architecture, as the &lt;i&gt;C. auris gcn5&lt;/i&gt;Δ mutant demonstrated a significant increase in cell-surface β-glucan exposure and chitin content. Additionally, we observed that Gcn5 modulates susceptibility to caspofungin and was required for fungal survival when challenged with primary murine macrophages and neutrophils &lt;i&gt;ex vivo&lt;/i&gt;. Furthermore, disruption of &lt;i&gt;GCN5&lt;/i&gt; causes virulence attenuation in a murine model of disseminated candidiasis. Lastly, lysine acetyltransferase inhibitor cyclopentanone, 2-[4-(4-chlorophenyl)-2-thiazolyl] hydrazone displayed antifungal activity either alone or in combination with caspofungin against the drug-resistant &lt;i&gt;C. auris&lt;/i&gt; wild-type strain. Collectively, these data provide new insights into the mechanisms of antifungal drug resistance and &lt;i&gt;C. auris&lt;/i&gt;-host interactions and suggest Gcn5 lysine acetyltransferase as a potential target for antifungal therapy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Invasive fungal diseases affect approximately 6.5 million people every year, of which about 2.5 million people die worldwide. This number is expected to rise due to increasing numbers of immunosuppressed people, including the elderly, premature infants, organ transplant recipients, cancer, and HIV/AIDS patients. The Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) have both recently emphasized a critical need for the development of new antifungal therapeutics to address expanding drug resistance among human fungal pathogens. The necessity of new antifungal drugs is also underscored by the fact that mortality due to invasive candidiasis has remained unchanged for several decades. However, the discovery of new drugs acting on antifungal drug targets is complicated because fungi are eukaryotes. This greatly limits the number of feasible fungal-specific drug targets. One class of molecul","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0006925"},"PeriodicalIF":3.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605933","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":"Pathogen priming alters host transmission potential and predictors of transmissibility in a wild songbird species.","authors":"A E Leon, A E Fleming-Davies, J S Adelman, D M Hawley","doi":"10.1128/msphere.00886-24","DOIUrl":"10.1128/msphere.00886-24","url":null,"abstract":"<p><p>Pathogen reinfections occur widely, but the extent to which reinfected hosts contribute to ongoing transmission is often unknown despite its implications for host-pathogen dynamics. House finches (<i>Haemorhous mexicanus</i>) acquire partial protection from initial exposure to the bacterial pathogen <i>Mycoplasma gallisepticum</i> (MG), with hosts readily reinfected with homologous or heterologous strains on short timescales. However, the extent to which reinfected hosts contribute to MG transmission has not been tested. We used three pathogen priming treatments-none, intermediate (repeated low-dose priming), or high (single high-dose priming)-to test how prior pathogen priming alters the likelihood of transmission to a cagemate during index bird reinfection with a homologous or heterologous MG strain. Relative to unprimed control hosts, the highest priming level strongly reduced maximum pathogen loads and transmission success of index birds during reinfections. Reinfections with the heterologous strain, previously shown to be more virulent and transmissible than the homologous strain used, resulted in higher pathogen loads within high-primed index birds and showed higher overall transmission success regardless of host priming treatment. This suggests that inherent differences in strain transmissibility are maintained in primed hosts, leading to the potential for ongoing transmission during reinfections. Finally, among individuals, transmission was most likely from hosts harboring higher within-host pathogen loads. However, associations between disease severity and transmission probability were dependent on a given bird's priming treatment. Overall, our results indicate that reinfections can result in ongoing transmission, particularly where reinfections result from a highly transmissible strain, with potential implications for virulence evolution.IMPORTANCEAs COVID-19 dramatically illustrated, humans and other animals can become infected with the same pathogen multiple times. Because individuals already have defenses against pathogens that their immune systems encountered before, reinfections are likely less contagious to others, but this is rarely directly tested. We used a songbird species and two strains of its common bacterial pathogen to study how contagious hosts are when their immune systems have some degree of prior experience with a pathogen. We found that reinfected hosts are not as contagious as initially infected ones. However, the more transmissible of the two strains, which also causes more harm to its hosts, was able to multiply more readily than the other strain within reinfected hosts and was more contagious in both reinfected and first-infected hosts. This suggests that reinfections might favor more harmful pathogen strains that are better able to overcome immune defenses.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0088624"},"PeriodicalIF":3.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586376","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 complete genome sequence of the crayfish pathogen Candidatus <i>Paracoxiella cheracis</i> n.g. n.sp. provides insight into pathogenesis and the phylogeny of the Coxiellaceae family.","authors":"Danielle J Ingle, Calum J Walsh, Genevieve R Samuel, Ryan R Wick, Nadav Davidovich, Eleonora Fiocchi, Louise M Judd, Jennifer Elliman, Leigh Owens, Timothy P Stinear, Andrea Basso, Tobia Pretto, Hayley J Newton","doi":"10.1128/msphere.01002-24","DOIUrl":"https://doi.org/10.1128/msphere.01002-24","url":null,"abstract":"<p><p>The Coxiellaceae bacterial family, within the order Legionellales, is defined by a collection of poorly characterized obligate intracellular bacteria. The zoonotic pathogen and causative agent of human Q fever, <i>Coxiella burnetii</i>, represents the best-characterized member of this family. Coxiellaceae establish replicative niches within diverse host cells and rely on their host for survival, making them challenging to isolate and cultivate within a laboratory setting. Here, we describe a new genus within the Coxiellaceae family that has been previously shown to infect economically significant freshwater crayfish. Using culture-independent long-read metagenomics, we reconstructed the complete genome of this novel organism and demonstrate that the species previously referred to as Candidatus <i>Coxiella cheraxi</i> represents a novel genus within this family, herein denoted Candidatus <i>Paracoxiella cheracis</i>. Interestingly, we demonstrate that Candidatus <i>P. cheracis</i> encodes a complete, putatively functional Dot/Icm type 4 secretion system that likely mediates the intracellular success of this pathogen. <i>In silico</i> analysis defined a unique repertoire of Dot/Icm effector proteins and highlighted homologs of several important <i>C. burnetii</i> effectors, including a homolog of CpeB that was demonstrated to be a Dot/Icm substrate in <i>C. burnetii</i>.IMPORTANCEUsing long-read sequencing technology, we have uncovered the full genome sequence of Candidatus <i>Paracoxiella cheracis</i>, a pathogen of economic importance in aquaculture. Analysis of this sequence has revealed new insights into this novel member of the Coxiellaceae family, demonstrating that it represents a new genus within this poorly characterized family of intracellular organisms. Importantly, the genome sequence reveals invaluable information that will support diagnostics and potentially both preventative and treatment strategies within crayfish breeding facilities. Candidatus <i>P. cheracis</i> also represents a new member of Dot/Icm pathogens that rely on this system to establish an intracellular niche. Candidatus <i>P. cheracis</i> possesses a unique cohort of putative Dot/Icm substrates that constitute a collection of new eukaryotic cell biology-manipulating effector proteins.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0100224"},"PeriodicalIF":3.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586401","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":"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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853005/pdf/","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":"OA","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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852725/pdf/","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":"OA","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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853014/pdf/","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":"OA","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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852849/pdf/","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":"OA","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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852746/pdf/","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":"OA","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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11852992/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}