Adnan Hodžić, Gorana Veinović, Amer Alić, David Seki, Martin Kunert, Georgi Nikolov, Ratko Sukara, Jovana Šupić, Snežana Tomanović, David Berry
{"title":"A metalloprotease secreted by an environmentally acquired gut bacterium hinders <i>Borrelia afzelii</i> colonization in <i>Ixodes ricinus</i>.","authors":"Adnan Hodžić, Gorana Veinović, Amer Alić, David Seki, Martin Kunert, Georgi Nikolov, Ratko Sukara, Jovana Šupić, Snežana Tomanović, David Berry","doi":"10.3389/fcimb.2024.1476266","DOIUrl":"https://doi.org/10.3389/fcimb.2024.1476266","url":null,"abstract":"<p><p>Although the importance of the microbiome in the context of tick biology and vector competence has recently come into a broader research focus, the field is still in its infancy and the complex ecological interactions between the tick residential bacteria and pathogens are obscure. Here, we show that an environmentally acquired gut bacterium has the potential to impair <i>Borrelia afzelii</i> colonization within the tick vector through a secreted metalloprotease. Oral introduction of either <i>Bacillus cereus</i> LTG-1 isolate or its purified enhancin (<i>Bc</i>Enhancin) protein significantly reduces <i>B. afzelii</i> burden in the guts of <i>Ixodes ricinus</i> ticks. This effect is attributed to the ability of <i>Bc</i>Enhancin to degrade a glycan-rich peritrophic matrix (PM), which is a gut protective barrier essential for <i>Borrelia</i> survival. Our study highlights the importance of the gut microbiome in determining tick vector competence and provides a deeper mechanistic insight into the complex network of interactions between <i>Borrelia</i>, the tick, and the tick microbiome.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1476266"},"PeriodicalIF":4.6,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Identification of porcine PARP11 as a restricted factor for pseudorabies virus.","authors":"Chunyun Qi, Dehua Zhao, Xi Wang, Lanxin Hu, Yao Wang, Heyong Wu, Feng Li, Jian Zhou, Tianyi Zhang, Aosi Qi, Yuran Huo, Qiuse Tu, Shuyu Zhong, Hongming Yuan, Dongmei Lv, Shouqing Yan, Hongsheng Ouyang, Daxin Pang, Zicong Xie","doi":"10.3389/fcimb.2024.1414827","DOIUrl":"10.3389/fcimb.2024.1414827","url":null,"abstract":"<p><strong>Introduction: </strong>PRV infection in swine can cause devastating disease and pose a potential threat to humans. Advancing the interplay between PRV and host is essential to elucidate the pathogenic mechanism of PRV and identify novel anti-PRV targets.</p><p><strong>Methods: </strong>PARP11-KO PK-15 cells were firstly constructed by CRISPR/Cas9 technology. Next, the effect of PARP11-KO on PRV infection was determined by RT-qPCR, TCID50 assay, RNA-seq, and western blot.</p><p><strong>Results and discussion: </strong>In this study, we identified PARP11 as a host factor that can significantly affect PRV infection. Inhibition of PARP11 and knockout of PARP11 can significantly promoted PRV infection. Subsequently, we further found that PARP11 knockout upregulated the transcription of NXF1 and CRM1, resulting in enhanced transcription of viral genes. Furthermore, we also found that PARP11 knockout could activate the autophagy pathway and suppress the mTOR pathway during PRV infection. These findings could provide insight into the mechanism in which PARP11 participated during PRV infection and offer a potential target to develop anti-PRV therapies.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1414827"},"PeriodicalIF":4.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marc Herb, Valentin Schatz, Karina Hadrian, Deniz Hos, Bohdan Holoborodko, Jonathan Jantsch, Natascha Brigo
{"title":"Macrophage variants in laboratory research: most are well done, but some are RAW.","authors":"Marc Herb, Valentin Schatz, Karina Hadrian, Deniz Hos, Bohdan Holoborodko, Jonathan Jantsch, Natascha Brigo","doi":"10.3389/fcimb.2024.1457323","DOIUrl":"https://doi.org/10.3389/fcimb.2024.1457323","url":null,"abstract":"<p><p>Macrophages play a pivotal role in the innate immune response. While their most characteristic function is phagocytosis, it is important not to solely characterize macrophages by this activity. Their crucial roles in body development, homeostasis, repair, and immune responses against pathogens necessitate a broader understanding. Macrophages exhibit remarkable plasticity, allowing them to modify their functional characteristics in response to the tissue microenvironment (tissue type, presence of pathogens or inflammation, and specific signals from neighboring cells) swiftly. While there is no single defined \"macrophage\" entity, there is a diverse array of macrophage types because macrophage ontogeny involves the differentiation of progenitor cells into tissue-resident macrophages, as well as the recruitment and differentiation of circulating monocytes in response to tissue-specific cues. In addition, macrophages continuously sense and respond to environmental cues and tissue conditions, adjusting their functional and metabolic states accordingly. Consequently, it is of paramount importance to comprehend the heterogeneous origins and functions of macrophages employed in <i>in vitro</i> studies, as each available <i>in vitro</i> macrophage model is associated with specific sets of strengths and limitations. This review centers its attention on a comprehensive comparison between immortalized mouse macrophage cell lines and primary mouse macrophages. It provides a detailed analysis of the strengths and weaknesses inherent in these <i>in vitro</i> models. Finally, it explores the subtle distinctions between diverse macrophage cell lines, offering insights into numerous factors beyond the model type that can profoundly influence macrophage function.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1457323"},"PeriodicalIF":4.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Diagnostic value of effusion adenosine deaminase, γ-interferon release assay and effusion lactatedehy drogenase/effusion adenosine deaminase for tuberculous pleural effusion in patients aged 60 years and above.","authors":"Fei Guo, Chen Huimin, Wei Xia, Yilin Xu, Weijiang Jin, Fang Liu","doi":"10.3389/fcimb.2024.1444238","DOIUrl":"10.3389/fcimb.2024.1444238","url":null,"abstract":"<p><strong>Background: </strong>China is experiencing rapid growth in its population of older adults, which may lead to increased susceptibility to tuberculous pleural effusion (TPE) due to age-related changes in the immune system. This study aimed to investigate the diagnostic potential of multiple biomarkers in individuals aged 60 years and above with pleural effusion.</p><p><strong>Methods: </strong>A total of 519 adult patients from Ningbo First Hospital were included in the study, with 7 biomarkers and their ratios in serum and pleural effusion analyzed using logistic regression analysis. Effusion Adenosine Deaminase(ADA), γ-Interferon Release Assay(IGRA), and Effusion lactatedehy drogenase(LDH)/Effusion ADA were identified as valuable parameters for differentiating TPE from non-TPE, particularly in individuals aged 60 years and older.</p><p><strong>Results: </strong>Effusion ADA, IGRA, and Effusion LDH/Effusion ADA were identified as valuable parameters for the differential diagnosis of TPE from non-TPE, showing good diagnostic performance in individuals aged 60 years and older. The combined diagnosis of these three indexes achieved the highest diagnostic accuracy for TPE in this age group, with an AUC of 0.925, sensitivity of 85.23%, and specificity of 89.57%.</p><p><strong>Conclusions: </strong>Overall, the study highlights the importance of using multiple indicators for a combined diagnosis to improve diagnostic efficacy in detecting tuberculous pleurisy in older individuals as for young patients.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1444238"},"PeriodicalIF":4.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Host-dependent C-to-U RNA editing in SARS-CoV-2 creates novel viral genes with optimized expressibility.","authors":"Pirun Zhang, Wenli Zhang, Jiahuan Li, Huiying Liu, Yantong Yu, Xiaoping Yang, Wenqing Jiang","doi":"10.3389/fcimb.2024.1476605","DOIUrl":"https://doi.org/10.3389/fcimb.2024.1476605","url":null,"abstract":"<p><p>Rampant C-to-U RNA editing drives the mutation and evolution of SARS-CoV-2. While much attention has been paid to missense mutations, the C-to-U events leading to AUG and thus creating novel ORFs were uninvestigated. By utilizing the public time-course mutation data from the worldwide SARS-CoV-2 population, we systematically identified the \"AUG-gain mutations\" caused by C-to-U RNA editing. Synonymous mutations were of special focus. A total of 58 synonymous C-to-U sites are able to create out-of-frame AUG in coding sequence (CDS). These 58 synonymous sites showed significantly higher allele frequency (AF) and increasing rate (<i>d</i>AF/<i>d</i>t) than other C-to-U synonymous sites in the SARS-CoV-2 population, suggesting that these 58 AUG-gain events conferred additional benefits to the virus and are subjected to positive selection. The 58 predicted new ORFs created by AUG-gain events showed the following advantages compared to random expectation: they have longer lengths, higher codon adaptation index (CAI), higher Kozak scores, and higher tRNA adaptation index (tAI). The 58 putatively novel ORFs have high expressibility and are very likely to be functional, providing an explanation for the positive selection on the 58 AUG-gain mutations. Our study proposed a possible mechanism of the emergence of <i>de novo</i> genes in SARS-CoV-2. This idea should be helpful in studying the mutation and evolution of SARS-CoV-2.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1476605"},"PeriodicalIF":4.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Insights into the intestinal microbiota of <i>Exopalaemon annandalei</i> and <i>Exopalaemon carinicauda</i> in the Yangtze River estuary.","authors":"Jiahao Wang, Guangpeng Feng, Zhiqiang Han, Tao Zhang, Jinhui Chen, Jianhui Wu","doi":"10.3389/fcimb.2024.1420928","DOIUrl":"https://doi.org/10.3389/fcimb.2024.1420928","url":null,"abstract":"<p><p>The gut microbiota plays a crucial role in food webs, carbon cycling, and related elements. <i>Exopalaemon annandalei</i> and <i>Exopalaemon carinicauda</i> are two important forage species in the Yangtze River estuary with extremely similar living habits and morphological characteristics. Exploring the microorganisms in the guts of these two shrimp species can help us understand the survival status of forage species and gut microbiota in the Yangtze River estuary. Therefore, this study analyzed the similarities and differences in the intestinal flora of <i>E. annandalei</i> and <i>E. carinicauda</i> through high-throughput sequencing of 16S rRNA gene amplicons. The results showed that the dominant bacteria in the intestinal flora of <i>E. annandalei</i> and <i>E. carinicauda</i> at the phylum level were Proteobacteria and Firmicutes, respectively. At the genus level, the intestinal flora had higher concentrations of <i>Psychrobacter</i>, <i>Bacillus</i>, <i>Pseudomonas</i>, <i>Acinetobacter</i>, and <i>Macrococcus</i>. In both shrimp species, the contents of <i>Acinetobacter</i> and <i>Macrococcus</i> were higher in spring than in winter. The most important potential functions of the intestinal microbiota were amino acid metabolism and purine metabolism. Additionally, the functions of metabolism and diseases in the intestinal microbiota of <i>E. annandalei</i> were greatly influenced by the season. Furthermore, the experimental results indicated that a lower ratio of <i>Firmicutes</i> to <i>Bacteroidetes</i> was associated with a larger body weight in shrimp. Overall, this study provides a theoretical reference for understanding the intestinal bacterial community of shrimp in estuaries and the healthy cultivation of <i>E. annandalei</i> and <i>E. carinicauda</i>.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1420928"},"PeriodicalIF":4.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evaluation of immune sensor responses to a viral small noncoding RNA.","authors":"Mehmet Kara, Scott A Tibbetts","doi":"10.3389/fcimb.2024.1459256","DOIUrl":"https://doi.org/10.3389/fcimb.2024.1459256","url":null,"abstract":"<p><strong>Introduction: </strong>Gammaherpesviruses are widespread pathogens causing persistent infections linked to the development of numerous types of lymphomas in humans. During latency, most of the viral protein-coding genes are suppressed, facilitating evasion of adaptive immune recognition of protein antigens. In contrast, many noncoding RNA (ncRNA) molecules are expressed in infected cells and can regulate key cellular pathways while simultaneously evading adaptive immune recognition. To counteract this, many cells express internal pattern recognition receptors that can intrinsically sense ongoing infections and initiate cellular defenses. Murine gammaherpesvirus 68 (MHV68) is a valuable model to study <i>in vivo</i> aspects of gammaherpesvirus pathogenesis. The MHV68 ncRNA TMER4 (tRNA-miRNA-encoding RNA 4) promotes lymph node egress of infected B cells: in the absence of TMER4, MHV68-infected B cells accumulate in the lymph node in a manner similar to B cells activated through specific antigen encounter.</p><p><strong>Method: </strong>We hypothesized that TMER4 may alter intrinsic immune activation. In research described here, we aimed to explore the immunomodulatory functions of TMER4 by evaluating its impact on signaling through the critical immune sensors Toll-like receptor 4 (TLR4), TLR3, TLR7, and retinoic acid-inducible gene I (RIG-I). To accomplish this, we developed a system to test noncoding RNAs using commercially available reporter cell lines. We optimized the experimental procedure to ensure ncRNA expression and to quantify immune sensory molecule induction or inhibition by the expressed ncRNA.</p><p><strong>Results and discussion: </strong>Expression of TMER4 RNAs from plasmid constructs did not alter TLR or RIG-I signaling. This study provides a clear experimental framework that can be applied to test other small ncRNAs for their impact on various innate immune sensor proteins.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1459256"},"PeriodicalIF":4.6,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shaowen Jin, Wa Zhong, Bo Li, Kaimei Wang, Dongming Lai
{"title":"Multidimensional analysis of the impact of Gemmatimonas, Rhodothermus, and Sutterella on drug and treatment response in colorectal cancer.","authors":"Shaowen Jin, Wa Zhong, Bo Li, Kaimei Wang, Dongming Lai","doi":"10.3389/fcimb.2024.1457461","DOIUrl":"https://doi.org/10.3389/fcimb.2024.1457461","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer is the third most prevalent cancer across the globe. Despite a diversity of treatment methods, the recurrence and mortality rates of the disease remain high. Recent studies have revealed a close association of the gut microbiota with the occurrence, development, treatment response, and prognosis of colorectal cancer.</p><p><strong>Objective: </strong>This study aims to integrate transcriptome and microbiome data to identify colorectal cancer subtypes associated with different gut microbiota and evaluate their roles in patient survival prognosis, tumor microenvironment (TME), and drug treatment response.</p><p><strong>Methods: </strong>An integrated analysis of microbiome data was conducted on samples of colorectal cancer from public databases. Based on this, two tumor subtypes (C1 and C2) closely associated with patient survival prognosis were identified and a risk score model was constructed. The survival status, clinical parameters, immune scores, and other features were analyzed in-depth, and the sensitivity of various potential drugs was examined.</p><p><strong>Results: </strong>A thorough examination of microbiome information obtained from colorectal cancer patients led to the identification of two primary tumor clusters (C1 and C2), exhibiting notable variations in survival outcomes. Patients with the C1 subtype were closely associated with better prognosis, while those with the C2 subtype had higher gut microbial richness and poorer survival prognosis. A predictive model utilizing the microbiome data was developed to accurately forecast the survival outcome of patients with colorectal cancer. The TME scores provided a biological basis for risk assessment in high-risk (similar to the C2 subtype) patient cohorts. Evaluation of the sensitivity of different subtypes to various potential drugs, indicated the critical importance of personalized treatment. Further analysis showed good potential of the developed risk-scoring model in predicting immune checkpoint functions and treatment response of patients, which may be crucial in guiding the selection of immunotherapy strategies for patients with colorectal cancer.</p><p><strong>Conclusion: </strong>This study, through a comprehensive analysis of colorectal cancer microbiome, immune microenvironment, and drug sensitivity, enhances the current understanding of the multidimensional interactions of colorectal cancer and provides important clinical indications for improving future treatment strategies. The findings offer a new perspective on improving treatment response and long-term prognosis of patients with CRC through the regulation of microbiota or the utilization of biomarkers provided by it.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1457461"},"PeriodicalIF":4.6,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Gut bacteria: an etiological agent in human pathological conditions.","authors":"Md Minarul Islam, Nasir Uddin Mahbub, Seong-Tshool Hong, Hea-Jong Chung","doi":"10.3389/fcimb.2024.1291148","DOIUrl":"https://doi.org/10.3389/fcimb.2024.1291148","url":null,"abstract":"<p><p>Through complex interactions with the host's immune and physiological systems, gut bacteria play a critical role as etiological agents in a variety of human diseases, having an impact that extends beyond their mere presence and affects the onset, progression, and severity of the disease. Gaining a comprehensive understanding of these microbial interactions is crucial to improving our understanding of disease pathogenesis and creating tailored treatment methods. Correcting microbial imbalances may open new avenues for disease prevention and treatment approaches, according to preliminary data. The gut microbiota exerts an integral part in the pathogenesis of numerous health conditions, including metabolic, neurological, renal, cardiovascular, and gastrointestinal problems as well as COVID-19, according to recent studies. The crucial significance of the microbiome in disease pathogenesis is highlighted by this role, which is comparable to that of hereditary variables. This review investigates the etiological contributions of the gut microbiome to human diseases, its interactions with the host, and the development of prospective therapeutic approaches. To fully harness the benefits of gut microbiome dynamics for improving human health, future research should address existing methodological challenges and deepen our knowledge of microbial interactions.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1291148"},"PeriodicalIF":4.6,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142498142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The RNA m<sup>5</sup>C methyltransferase NSUN1 modulates human malaria gene expression during intraerythrocytic development.","authors":"Ruoyu Tang, Yanting Fan, BinBin Lu, Qunfeng Jiang, Xinyu Cheng, Zuping Zhang, Li Shen, Xiaomin Shang","doi":"10.3389/fcimb.2024.1474229","DOIUrl":"10.3389/fcimb.2024.1474229","url":null,"abstract":"<p><strong>Introduction: </strong><i>Plasmodium falciparum</i> is the most damaging malaria pathogen and brings a heavy burden to global health. Host switching and morphological changes in <i>P. falciparum</i> are dependent on an effective gene expression regulatory system. C5 methylation of cytosines is a common RNA modification in eukaryotes, and the NSUN family are essential m<sup>5</sup>C modification executors. Currently, little is known about this family in <i>Plasmodium</i> spp. In this study, we focus on exploring the function of <i>PfNSUN1</i> protein.</p><p><strong>Methods: </strong>An efficient CRISPR/Cas9 gene editing technique was applied to construct the <i>PfNSUN1</i> knockdown strain. The knockdown efficiency was confirmed by growth curves and western blot experiments. The knockdown transcriptome data was acquired to find differentially expressed genes, and target genes of <i>PfNSUN1</i> protein were identified by RNA immunoprecipitation and high-throughput sequencing experiments.</p><p><strong>Results: </strong>The efficiency of <i>PfNSUN1</i> protein down-regulated was about 34%. RNA-seq data revealed that differentially expressed genes were mainly down-regulated. And there were 224, 278, 556 genes that were down-regulated with more than 2-fold changes and p-adj<0.05 at ring, trophozoite and schizont stages, respectively. <i>PfNSUN1</i> protein was significantly enriched on 154 target genes, including 28S ribosomal RNA and <i>pfap2-g5</i> transcription factor.</p><p><strong>Discussion: </strong><i>PfNSUN1</i> is a crucial RNA post-transcriptional modification protein in <i>P. falciparum</i>. It plays a pivotal role in regulating gene expression and parasite growth by targeting 28S ribosomal RNA and <i>pfap2-g5</i> transcription factor.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1474229"},"PeriodicalIF":4.6,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142462111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}