Medical Microbiology and Immunology最新文献

筛选
英文 中文
Regulatory T cells suppress TLR9-induced formation of intrahepatic myeloid-cell aggregates for T cell population expansion in liver. 调节性T细胞抑制tlr9诱导的肝内骨髓细胞聚集体的形成,以促进肝内T细胞群的扩增。
IF 5.5 3区 医学
Medical Microbiology and Immunology Pub Date : 2025-05-14 DOI: 10.1007/s00430-025-00834-2
Yanqin Du, Mengxiao Zhao, Xiaoqing Zeng, Shichuan Wang, Qin Wang, Liwei Chen, Xuecheng Yang, Xuemei Feng, Mengji Lu, Ulf Dittmer, Kathrin Sutter, Xin Zheng, Dongliang Yang, Chunli Xu, Jia Liu
{"title":"Regulatory T cells suppress TLR9-induced formation of intrahepatic myeloid-cell aggregates for T cell population expansion in liver.","authors":"Yanqin Du, Mengxiao Zhao, Xiaoqing Zeng, Shichuan Wang, Qin Wang, Liwei Chen, Xuecheng Yang, Xuemei Feng, Mengji Lu, Ulf Dittmer, Kathrin Sutter, Xin Zheng, Dongliang Yang, Chunli Xu, Jia Liu","doi":"10.1007/s00430-025-00834-2","DOIUrl":"10.1007/s00430-025-00834-2","url":null,"abstract":"<p><p>Toll-like receptor (TLR) 9 ligand has been reported to induce the formation of intrahepatic myeloid-cell aggregates for T cell population expansion (iMATEs), which enhances responses of cytotoxic T lymphocytes (CTLs). However, little is known about how the formation of iMATEs is regulated. Previously, various studies have demonstrated that regulatory T cells (Tregs) can suppress CTL responses through soluble cytokines or co-inhibitory molecules. It's unclear whether and how Tregs regulate the formation of iMATEs. In this study, we investigated whether Tregs are involved in regulating TLR9-induced iMATEs formation and the mechanisms behind it by using different gene knockout mice and blocking antibodies. We observed that intravenous injection of TLR9 ligand CpG induced significant iMATEs formation, accompanied by a marked increase in the number of Tregs infiltrating the liver as well as upregulation of IL-10 in both peripheral blood and liver. Importantly, depletion of Tregs either by anti-CD4, anti-CD25 blocking antibodies or diphtheria toxin (DT) in DEREG transgenic mice resulted in enhanced CpG-induced iMATEs formation. Conversely, knocking out IL-10 led to increased intrahepatic Treg infiltration and decreased CpG ODN-induced iMATEs formation. Consistently, depleting Kupffer cells (KCs), one of the main source of IL-10, also resulted in reduced formation of iMATEs. In conclusion, our results suggest that IL-10 suppresses Treg infiltration in the liver and thus promote CpG ODN-induced iMATEs formation. These results fill the gap in our understanding of the intrahepatic regulation mechanism of iMATEs formation.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"214 1","pages":"24"},"PeriodicalIF":5.5,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Complement C5a promotes human retinal pigment epithelial cell viability and migration through SLC38A1-mediated glutamine metabolism. 补体C5a通过slc38a1介导的谷氨酰胺代谢促进人视网膜色素上皮细胞的活力和迁移。
IF 5.5 3区 医学
Medical Microbiology and Immunology Pub Date : 2025-05-13 DOI: 10.1007/s00430-025-00832-4
Ye Sun, Yifan Hu, Shasha Luo
{"title":"Complement C5a promotes human retinal pigment epithelial cell viability and migration through SLC38A1-mediated glutamine metabolism.","authors":"Ye Sun, Yifan Hu, Shasha Luo","doi":"10.1007/s00430-025-00832-4","DOIUrl":"https://doi.org/10.1007/s00430-025-00832-4","url":null,"abstract":"<p><p>The pathological basis of many visual disorders involves the abnormal viability and migration of retinal pigment epithelium (RPE) cells. Complement response disorder is a significant pathogenic factor causing some autoimmune and inflammation diseases. The complement activation product anaphylatoxin C5a signaling pathway may be associated with RPE cell dysfunction. This study aimed to analyze the molecular mechanisms by which C5a affects RPE cell viability and migration. Recombinant human complement component C5a protein stimulated RPE cells. Cell biological behavior, including cell viability, invasion, and migration were analyzed with Cell Counting Kit-8 and transwell methods. Bioinformatics analysis identified the differentially expressed genes (DEGs) involved in C5a-treated RPE cells based on RNA sequencing. SLC38A1 was knocked down or overexpressed by vector transfection to investigate its involvement in C5a-stimulated RPE cells. C5a promotes RPE cell viability and migration. C5a-induced DEGs are enriched in migration-associated pathways. C5a increased SLC38A1, and SLC38A1 knockdown or overexpression inhibited or promoted RPE cell viability and migration. Glutaminase inhibition abrogated the promoting effect of C5a and SLC38A1 on cell biological behaviors. METTL3-HNRNPC-mediated m6A modification mediated C5a-induced SLC38A1. C5a, METTL3, and SLC38A1 constituted a signaling axis in regulating cell biological behaviors of C5a-treated RPE cells. C5a promotes RPE cell viability and migration, and SLC38A1-mediated improved glutamine metabolism is the downstream signal pathway of the C5a complement pathway. The C5a complement system may target the SLC38A1 to promote RPE cell migration.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"214 1","pages":"22"},"PeriodicalIF":5.5,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impact of Staphylococcus aureus colonization and skin abscesses on formation of human anti-αGal antibodies. 金黄色葡萄球菌定植和皮肤脓肿对人抗α - gal抗体形成的影响。
IF 5.5 3区 医学
Medical Microbiology and Immunology Pub Date : 2025-05-13 DOI: 10.1007/s00430-025-00833-3
Jens Magnus Bernth Jensen, Khoa Manh Dinh, Lotte Hindhede, Lise Tornvig Erikstrup, Annette Gudmann Hansen, Kirstine Mejlstrup Hymøller, Sisse Rye Ostrowski, Ole B V Pedersen, Stig Hill Christiansen, Uffe B Skov Sørensen, Steffen Thiel, Christian Erikstrup
{"title":"Impact of Staphylococcus aureus colonization and skin abscesses on formation of human anti-αGal antibodies.","authors":"Jens Magnus Bernth Jensen, Khoa Manh Dinh, Lotte Hindhede, Lise Tornvig Erikstrup, Annette Gudmann Hansen, Kirstine Mejlstrup Hymøller, Sisse Rye Ostrowski, Ole B V Pedersen, Stig Hill Christiansen, Uffe B Skov Sørensen, Steffen Thiel, Christian Erikstrup","doi":"10.1007/s00430-025-00833-3","DOIUrl":"10.1007/s00430-025-00833-3","url":null,"abstract":"<p><p>IgG antibodies against terminal galactose-α-1,3-galactose (anti-αGal antibodies) are naturally occurring in humans, but their origins remain poorly understood. These antibodies target various microorganisms including Staphylococcus aureus, a common nasal commensal and the major cause of skin abscesses. This study investigates the impact of S. aureus colonization and abscess events on plasma anti-αGal antibody levels. We measured plasma anti-αGal antibody levels using a quantitative immunoassay in: (i) 101 pairs of healthy individuals with and without nasal S. aureus colonization, (ii) 106 healthy individuals before and after abscess formation, and (iii) 43 patients with recurrent skin abscesses compared with 75 patient controls and 60 healthy controls. We observed a 35% reduction (95%CI: 7-54%) in anti-αGal antibody levels in nasal S. aureus carriers. Conversely, we found a 30% increase (95%CI: 4-66%) in individuals within 187 days post-skin abscess, and patients with recurrent skin abscesses exhibited 81% higher (95%CI: 14-190%) levels than patient controls, and 110% higher (95%CI: 39-230%) than healthy controls. This study suggests that skin abscesses lead to elevated plasma anti-αGal antibody levels and that these antibodies might convey or correlate with mucosal immunity to S. aureus.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"214 1","pages":"23"},"PeriodicalIF":5.5,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impact of vancomycin and Clostridioides difficile on the secretome and pathogenicity of Clostridium innocuum. 万古霉素和艰难梭菌对无害梭菌分泌组和致病性的影响。
IF 5.5 3区 医学
Medical Microbiology and Immunology Pub Date : 2025-05-08 DOI: 10.1007/s00430-025-00831-5
Yi-Ywan M Chen, Kun-Yi Chien, Hui-Ru Shieh, Cai-Jie Luo, Yu-Xun Chang, Chuan Chiang-Ni, Chih-Ho Lai, Cheng-Hsun Chiu
{"title":"Impact of vancomycin and Clostridioides difficile on the secretome and pathogenicity of Clostridium innocuum.","authors":"Yi-Ywan M Chen, Kun-Yi Chien, Hui-Ru Shieh, Cai-Jie Luo, Yu-Xun Chang, Chuan Chiang-Ni, Chih-Ho Lai, Cheng-Hsun Chiu","doi":"10.1007/s00430-025-00831-5","DOIUrl":"https://doi.org/10.1007/s00430-025-00831-5","url":null,"abstract":"<p><p>Clostridium innocuum, a member of the human gut microbiome with intrinsic resistance to vancomycin, has been increasingly associated with inflammatory bowel diseases (IBD). Clinical observations indicate that co-infection with Clostridioides difficile and C. innocuum could lead to poorer clinical remission in ulcerative colitis; however, the pathogenic mechanism of C. innocuum remains unclear. Here, we investigated the effects of vancomycin and C. difficile on C. innocuum secretomes and the functions of the modified secretomes on C. innocuum pathogenicity. The results indicated that, compared to co-culturing with C. difficile, vancomycin was more effective in stimulating the secretion of proteins without a signal peptide, whereas C. difficile was better at promoting the secretion of classical secretory proteins. Based on these results, we further analyzed the effects of three abundant classical secretory proteins on C. innocuum virulence utilizing recombinant proteins. The results demonstrated that the NlpC/P60-containing protein (NlpC/P60) can enhance C. innocuum biofilm formation and adherence to HT-29 cells. Additionally, NlpC/P60, D-Ala-D-Ala carboxypeptidase, and a polysaccharide deacetylase were able to stimulate IL-8 production of HT-29 cells and TNF-α production of Raw264.7 macrophages. Additionally, recombinant NlpC/P60 and polysaccharide deacetylase exhibited cytotoxicity on Raw264.7 cells at 48 h. As the production of IL-8 and TNF-α is closely associated with IBD development, it is suggested that C. innocuum secretomes, under the influence of vancomycin or C. difficile, could contribute to IBD progression by enhancing inflammation and host-pathogen interactions.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"214 1","pages":"21"},"PeriodicalIF":5.5,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction: Deciphering long-term immune effects of HIV-1/SARS-CoV-2 co-infection: a longitudinal study. 更正:解读HIV-1/SARS-CoV-2合并感染的长期免疫效应:一项纵向研究。
IF 5.5 3区 医学
Medical Microbiology and Immunology Pub Date : 2025-05-06 DOI: 10.1007/s00430-025-00829-z
Elena Vazquez-Alejo, María De La Sierra Espinar-Buitrago, Esmeralda Magro-Lopez, Laura Tarancon-Diez, Cristina Díez, José Ignacio Bernardino, Anna Rull, Ignacio De Los Santos, Roberto Alonso, Angielys Zamora, José Luis Jiménez, Mª Ángeles Muñoz-Fernández
{"title":"Correction: Deciphering long-term immune effects of HIV-1/SARS-CoV-2 co-infection: a longitudinal study.","authors":"Elena Vazquez-Alejo, María De La Sierra Espinar-Buitrago, Esmeralda Magro-Lopez, Laura Tarancon-Diez, Cristina Díez, José Ignacio Bernardino, Anna Rull, Ignacio De Los Santos, Roberto Alonso, Angielys Zamora, José Luis Jiménez, Mª Ángeles Muñoz-Fernández","doi":"10.1007/s00430-025-00829-z","DOIUrl":"https://doi.org/10.1007/s00430-025-00829-z","url":null,"abstract":"","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"214 1","pages":"20"},"PeriodicalIF":5.5,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Profiling the nasopharyngeal Microbiome in patients with community-acquired pneumonia caused by Streptococcus pneumoniae: diagnostic challenges and ecological insights. 分析肺炎链球菌引起的社区获得性肺炎患者的鼻咽微生物组:诊断挑战和生态学见解。
IF 5.5 3区 医学
Medical Microbiology and Immunology Pub Date : 2025-04-10 DOI: 10.1007/s00430-025-00828-0
Cristina Zubiria-Barrera, Linda Yamba Yamba, Tilman E Klassert, Malena Bos, Jonas Ahl, Lisa Wasserstrom, Hortense Slevogt, Kristian Riesbeck
{"title":"Profiling the nasopharyngeal Microbiome in patients with community-acquired pneumonia caused by Streptococcus pneumoniae: diagnostic challenges and ecological insights.","authors":"Cristina Zubiria-Barrera, Linda Yamba Yamba, Tilman E Klassert, Malena Bos, Jonas Ahl, Lisa Wasserstrom, Hortense Slevogt, Kristian Riesbeck","doi":"10.1007/s00430-025-00828-0","DOIUrl":"https://doi.org/10.1007/s00430-025-00828-0","url":null,"abstract":"<p><p>Community-acquired pneumonia (CAP) is a significant health threat for adults. Although conjugate vaccines have reduced pneumococcal CAP incidence in children, Streptococcus pneumoniae-related CAP remains prevalent among older adults. The nasopharynx acts as a reservoir for S. pneumoniae, yet the interplay between this pathogen and the nasopharyngeal microbiome during and after pneumonia remains poorly understood. This study included 61 adult patients diagnosed with pneumococcal CAP and 61 matched healthy controls. An S. pneumoniae-specific PCR, urine antigen tests and bacterial cultures were performed. Nasopharyngeal swabs collected at admission and three months post-infection were analyzed for microbiome dynamics through 16 S rRNA gene amplicon sequencing. 16 S rRNA gene amplicon sequencing revealed Streptococcus spp. in the majority of all nasopharyngeal samples during infection compared to the other diagnostic test performed. While overall bacterial biomass did not differ between groups, patients exhibited higher alpha diversity (p = 0.012) and lower microbiome stability post-infection. Beta diversity analysis distinguished infection from healthy status (p = 0.002). Taxonomic analysis showed similar core microbiota across groups, but Streptococcus spp. was significantly more abundant during infection, particularly in those patients with viral co-infections. Notably, unique significant bacterial interactions were identified both during and after infection, as well as in healthy states. A negative correlation was observed between Corynebacterium and Streptococcus spp. in infected patients, suggesting a potential antagonistic interaction between these taxa. The nasopharyngeal microbiome in patients with pneumococcal CAP demonstrates persistent disruption post-infection, characterized by lower resilience three months after acute illness. Additionally, we identified specific bacterial interplays during and after infection that differed from those in healthy donors. These bacterial dynamics might play critical roles in pathogen colonization resistance and infection prevention. Thus, our findings highlight the need for further investigation into microbial interactions and potential microbiome-based therapies for respiratory infections, particularly in vulnerable populations.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"214 1","pages":"19"},"PeriodicalIF":5.5,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11985632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mechanistic insights into LdCen1-LdDRP interaction facilitating UV-induced DNA damage repair in Leishmania donovani. LdCen1-LdDRP相互作用促进紫外线诱导的多诺瓦利什曼原虫DNA损伤修复的机制
IF 5.5 3区 医学
Medical Microbiology and Immunology Pub Date : 2025-04-09 DOI: 10.1007/s00430-025-00825-3
Roshanara, Rati Tandon, Niti Puri, A Selvapandiyan
{"title":"Mechanistic insights into LdCen1-LdDRP interaction facilitating UV-induced DNA damage repair in Leishmania donovani.","authors":"Roshanara, Rati Tandon, Niti Puri, A Selvapandiyan","doi":"10.1007/s00430-025-00825-3","DOIUrl":"https://doi.org/10.1007/s00430-025-00825-3","url":null,"abstract":"<p><p>Leishmania donovani is the causative agent of the fatal visceral leishmaniasis (VL) disease in humans in the tropical regions, mainly the Indian Subcontinent and Africa. We have previously described centrin1, a basal body associated cell division specific protein in this parasite important for the parasite's host intracellular stage. In this study, we identified a novel centrin1-binding protein called LdDRP through pull-down and MS/MS analysis, which is a homolog of the XPC protein of humans involved in DNA damage. The protein interaction with LdCen1 was also confirmed through peptide spectrum analysis against the UniProt database. Immunofluorescence analysis confirms that LdDRP is localized within the nucleus, suggesting the protein's possible role in DNA interaction. The overexpression of three LdDRP forms in the parasite, each fused with HA-tag (LdDRPF [full length] LdDRPN [only N-terminal], and LdDRPC [only C-terminal]), revealed that only LdDRPF and LdDRPC were able to support the retention of the parasite's shape and promote rapid division following the UV-damage recovery period. This was also correlated to the elevated expression level of both LdDRPC and LdCen1, by Western blot analysis soon after UV-C exposure in the parasites compared to control. The study emphasizes the role of the LdDRP, and its crucial domains involved in the DNA binding process, DNA damage response, and interaction with centrin, particularly in response to UV-C light-induced DNA damage.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"214 1","pages":"18"},"PeriodicalIF":5.5,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Interleukin-6 overexpression and elevated granulocyte-to-lymphocyte ratio indicate hepatic stress in experimental group a Streptococcus sepsis. 实验a组脓毒链球菌中白细胞介素-6过表达和粒细胞/淋巴细胞比值升高提示肝脏应激。
IF 5.5 3区 医学
Medical Microbiology and Immunology Pub Date : 2025-04-03 DOI: 10.1007/s00430-025-00826-2
Valerie Brunsch, Wendy Bergmann-Ewert, Brigitte Müller-Hilke, Johann Aleith
{"title":"Interleukin-6 overexpression and elevated granulocyte-to-lymphocyte ratio indicate hepatic stress in experimental group a Streptococcus sepsis.","authors":"Valerie Brunsch, Wendy Bergmann-Ewert, Brigitte Müller-Hilke, Johann Aleith","doi":"10.1007/s00430-025-00826-2","DOIUrl":"10.1007/s00430-025-00826-2","url":null,"abstract":"<p><p>Group A Streptococcus (GAS) is a pathogen that is capable of colonizing various infection sites and can potentially elicit an inadequate immune response that will lead to sepsis. The processes underlying this misdirected immune reaction remain poorly understood, and reliable biomarkers for indicating impending organ failure during sepsis are still missing. The present study aims to identify parameters that can predict the onset of end-organ damage in the course of sepsis. To that extent, we investigated key aspects of the immune response in early-phase sepsis following infection of different tissues in a mouse model, using Brefeldin A to link cytokine production to specific cell types through multi-parameter flow cytometry. Subcutaneous and intravenous GAS infections resulted in clinical sepsis, which was paralleled by peripheral blood lymphopenia. Intravenous infection in particular was associated with a higher bacterial burden in the liver that strongly correlated with an increased granulocyte-to-lymphocyte ratio of the peripheral blood. Strikingly, IL-6 overexpression was more pronounced in intravenous infection and strongly correlated with hepatic stress, indicated by elevated bacterial loads in the liver. Collectively, our data highlight the potential utility of IL-6 in conjunction with an elevated granulocyte-to-lymphocyte ratio as promising early indicators of concomitant liver stress in sepsis.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"214 1","pages":"17"},"PeriodicalIF":5.5,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CRISPR/Cas9-mediated deletion of a kinetoplast-associated gene attenuates virulence in Leishmania major parasites. CRISPR/ cas9介导的动质体相关基因缺失可减弱利什曼原虫主要寄生虫的毒力。
IF 5.5 3区 医学
Medical Microbiology and Immunology Pub Date : 2025-03-25 DOI: 10.1007/s00430-025-00827-1
Fatemeh Darzi, Ali Khamesipour, Minoo Tasbihi, Maryam Bahraminasab, Mahmoud Nateghi-Rostami
{"title":"CRISPR/Cas9-mediated deletion of a kinetoplast-associated gene attenuates virulence in Leishmania major parasites.","authors":"Fatemeh Darzi, Ali Khamesipour, Minoo Tasbihi, Maryam Bahraminasab, Mahmoud Nateghi-Rostami","doi":"10.1007/s00430-025-00827-1","DOIUrl":"10.1007/s00430-025-00827-1","url":null,"abstract":"<p><p>We employed a CRISPR/Cas9 technique in Leishmania major to evaluate its efficiency in editing a kDNA-associated gene, the universal minicircle sequence binding protein (UMSBP), which is involved in mitochondrial respiration and kinetoplast division. Using this toolkit, we generated UMSBP mNG-tagged and single knockout L. major (LmUMSBP<sup>+/-</sup>) parasites, which were confirmed by PCR, confocal microscopy and Western blot analyses. The growth rate of promastigotes in culture and their infectivity in macrophages were analysed in vitro. Mice were immunized with the LmUMSBP<sup>+/-</sup> mutant strain, and lesion size and parasite burden were measured upon challenge with wild-type (WT) L. major. Cytokines were quantified in supernatants of lymph node cell cultures. The results suggested successful expression and localization of the UMSBP mNG-tagged protein within the kinetoplast in both promastigote and intracellular amastigote forms, confirming the consistency of fluorescence tagging throughout various stages of the Leishmania life cycle. Attenuated LmUMSBP<sup>+/-</sup> parasites showed significantly reduced growth in culture (P < 0.05), increased apoptosis (P < 0.05) and downregulation of tryparedoxin peroxidase (TXNPx) and trypanothione synthetase (TryS) gene expression compared to WT L. major. LmUMSBP<sup>+/-</sup> mutant strains did not cause lesions in a susceptible BALB/c mouse model. Furthermore, immunization with LmUMSBP<sup>+/-</sup> parasites elicited a Th1 immune response, characterized by significantly higher IFN-γ and lower IL-4 production in cell culture (P < 0.001), which was associated with partial protection against WT L. major challenge, as evidenced by reduced parasite burden and lesion development in BALB/c mice. In this study, we successfully validated a practical CRISPR/Cas9 toolkit in L. major, targeting the kinetoplast-associated gene UMSBP. Our findings suggest that the UMSBP single-allele knockout mutant holds promise as a valuable tool for studying the role of the kinetoplast in Leishmania biology and as a potential candidate for further investigation as a live-attenuated vaccine against Leishmania infection.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"214 1","pages":"16"},"PeriodicalIF":5.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Deferiprone inhibits virulence and biofilm formation in Burkholderia cenocepacia. 去铁素抑制伯克霍尔德菌毒力和生物膜形成。
IF 5.5 3区 医学
Medical Microbiology and Immunology Pub Date : 2025-03-08 DOI: 10.1007/s00430-025-00824-4
Zhi-Wen Ding, Kai-Zhong Xu, Owias Iqbal Dar, Lu-Jun Yin, Ying-Jie Wang, Yun-Tong Liao, Peng Wang, Ai-Qun Jia
{"title":"Deferiprone inhibits virulence and biofilm formation in Burkholderia cenocepacia.","authors":"Zhi-Wen Ding, Kai-Zhong Xu, Owias Iqbal Dar, Lu-Jun Yin, Ying-Jie Wang, Yun-Tong Liao, Peng Wang, Ai-Qun Jia","doi":"10.1007/s00430-025-00824-4","DOIUrl":"10.1007/s00430-025-00824-4","url":null,"abstract":"<p><p>Burkholderia cenocepacia, an opportunistic pathogen, poses a significant threat to human health, necessitating the discovery of effective quorum sensing inhibitors (QSIs). In this study, the quorum sensing inhibitory effects of deferiprone (DFP) on the B. cenocepacia 162,638 were validated. Notably, DFP demonstrated an ability to inhibit and disrupt bacterial biofilms, reducing biofilm formation by 44.59% at 1/4 MIC (minimum inhibitory concentration) and 24.32% at 1/8 MIC concentrations. The study also investigated DFP's impact on motility, virulence, and QS signal levels. LC-MS/MS analysis showed a gradual reduction in the QS molecule C6-HSL as DFP concentrations increased. Additionally, DFP's non-hemolytic properties and safety profile, as verified in Galleria mellonella infection models, highlighted its biocompatibility. RT-qPCR results further indicated that DFP downregulated QS-related gene expression, particularly those involved in ferric uptake regulation protein (Fur). Molecular docking studies identified Fur as a key target for DFP's inhibitory action. Collectively, DFP was shown as a potential QSI with practical applications for controlling B. cenocepacia infections.</p>","PeriodicalId":18369,"journal":{"name":"Medical Microbiology and Immunology","volume":"214 1","pages":"15"},"PeriodicalIF":5.5,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信