Microbiology and Immunology最新文献

{"title":"Neutralization mechanism of human monoclonal antibodies against type B botulinum neurotoxin.","authors":"Takuhiro Matsumura, Mayu Kitamura, Sho Amatsu, Aki Yamaguchi, Nobuhide Kobayashi, Masahiro Yutani, Yukako Fujinaga","doi":"10.1111/1348-0421.13171","DOIUrl":"https://doi.org/10.1111/1348-0421.13171","url":null,"abstract":"<p><p>Botulism is a deadly neuroparalytic condition caused by the botulinum neurotoxin (BoNT) produced by Clostridium botulinum and related species. Toxin-neutralizing antibodies are the most effective treatments for BoNT intoxication. We generated human monoclonal antibodies neutralizing type B botulinum neurotoxin (BoNT/B), designated M2 and M4. The combination of these antibodies exhibited a strong neutralizing effect against BoNT/B toxicity. In this study, we analyzed the mechanisms of action of these antibodies in vitro. M4 binds to the C-terminus of the heavy chain (the receptor-binding domain) and inhibits BoNT/B binding to neuronal PC12 cells. Although M2 recognized the light (L) chain (the metalloprotease domain), it did not inhibit substrate (VAMP2) cleavage in the cleavage assay. M2 increased the surface localization of BoNT/B in PC12 cells at a later time point, suggesting that M2 inhibits the translocation of the L chain from synaptic vesicles to the cytosol. These results indicate that M2 and M4 inhibit the different processes of BoNT/B individually and that multistep inhibition is important for the synergistic effect of the combination of monoclonal antibodies. Our findings may facilitate the development of effective therapeutic antibodies against BoNTs.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Issue Information – Cover","authors":"","doi":"10.1111/1348-0421.13169","DOIUrl":"https://doi.org/10.1111/1348-0421.13169","url":null,"abstract":"<p><b>Cover photograph</b>: Overall cryo-EM maps and structures of SARS-CoV-2 EG.5.1 S protein. <i>Microbiol Immunol</i>: <i>68</i>:<i>305–330</i>. Article link here\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1348-0421.13169","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Issue Information – Cover","authors":"","doi":"10.1111/1348-0421.13168","DOIUrl":"10.1111/1348-0421.13168","url":null,"abstract":"<p><b>Cover photograph</b>: TMST of 11 STs identified from 41 E. faecium isolates. Each circle represents an ST, and the number in the middle of each circle represents the ST number. The size of each circle correlates with the number of isolates of that ST. Coloured pie charts indicate ABPC susceptibility and its proportion within each ST. The number of locus variants of seven loci that determine the STs between two circles is indicated by the number above the line connecting these circles. <i>Microbiol Immunol: 68:254-266</i>. Article link here\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1348-0421.13168","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141931617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Statins enhance extracellular release of hepatitis C virus particles through ERK5 activation.","authors":"Chie Aoki-Utsubo, Masanori Kameoka, Lin Deng, Muhammad Hanafi, Beti Ernawati Dewi, Pratiwi Sudarmono, Takaji Wakita, Hak Hotta","doi":"10.1111/1348-0421.13166","DOIUrl":"https://doi.org/10.1111/1348-0421.13166","url":null,"abstract":"<p><p>Statins, such as lovastatin, have been known to inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Statins were reported to moderately suppress hepatitis C virus (HCV) replication in cultured cells harboring HCV RNA replicons. We report here using an HCV cell culture (HCVcc) system that high concentrations of lovastatin (5-20 μg/mL) markedly enhanced the release of HCV infectious particles (virion) in the culture supernatants by up to 40 times, without enhancing HCV RNA replication, HCV protein synthesis, or HCV virion assembly in the cells. We also found that lovastatin increased the phosphorylation (activation) level of extracellular-signal-regulated kinase 5 (ERK5) in both the infected and uninfected cells in a dose-dependent manner. The lovastatin-mediated increase of HCV virion release was partially reversed by selective ERK5 inhibitors, BIX02189 and XMD8-92, or by ERK5 knockdown using small interfering RNA (siRNA). Moreover, we demonstrated that other cholesterol-lowering statins, but not dehydrolovastatin that is incapable of inhibiting HMG-CoA reductase and activating ERK5, enhanced HCV virion release to the same extent as observed with lovastatin. These results collectively suggest that statins markedly enhance HCV virion release from infected cells through HMG-CoA reductase inhibition and ERK5 activation.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction of knockout mutants in Mycobacterium intracellulare ATCC13950 strain using a thermosensitive plasmid containing negative selection marker rpsL<sup />.","authors":"Yoshitaka Tateishi, Akihito Nishiyama, Yuriko Ozeki, Sohkichi Matsumoto","doi":"10.1111/1348-0421.13167","DOIUrl":"https://doi.org/10.1111/1348-0421.13167","url":null,"abstract":"<p><strong>Background: </strong>Nontuberculous mycobacterial disease has emerged worldwide over the past 20 years. However, there are currently few reports on the established technique for constructing knockout mutants of nontuberculous mycobacteria. Therefore, gene recombination techniques for nontuberculous mycobacteria require further research.</p><p><strong>Results: </strong>We constructed vector pPR23LHR that harbors the ribosomal protein S12 gene (rpsL⁺) as a dominant negative selection marker and the hygromycin (Hyg) and lacZ cassettes as positive selection markers. We constructed knockout mutants of proteasomal genes, which we found to be required for hypoxic pellicle formation in Mycobacterium intracellulare by functional genomic analysis. The knockout mutants showed impaired hypoxic pellicle formation, consistent with previous data using epoxomicin, a proteasomal inhibitor.</p><p><strong>Conclusions: </strong>Our findings demonstrate that rpsL⁺ is an efficient dominant negative selection marker for gene recombination in nontuberculous mycobacteria. Our temperature-sensitive rpsL⁺ method for the construction of knockout mutants will facilitate functional assays to validate the virulence factors of nontuberculous mycobacteria and the pathogenesis of nontuberculous mycobacterial disease.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of a novel spotted fever group Rickettsia, “Candidatus Rickettsia kedanie,” in unfed larval chigger mites, Leptotrombidium scutellare","authors":"Motohiko Ogawa,&nbsp;Minenosuke Matsutani,&nbsp;Takashi Katayama,&nbsp;Nobuhiro Takada,&nbsp;Shinichi Noda,&nbsp;Mamoru Takahashi,&nbsp;Daisuke Kageyama,&nbsp;Nozomu Hanaoka,&nbsp;Hideki Ebihara","doi":"10.1111/1348-0421.13161","DOIUrl":"10.1111/1348-0421.13161","url":null,"abstract":"<p>Spotted fever group (SFG) rickettsia, the causative agent of SFG rickettsiosis, is predominantly carried by ticks, whereas <i>Orientia tsutusgamushi</i>, the causative agent of scrub typhus, is primarily transmitted by chigger mites in Japan. In this study, we attempted to isolate intracellular eubacteria from <i>Leptotrombidium scutellare</i>, a major vector of <i>O. tsutsugamushi</i>; moreover, we isolated an SFG rickettsia using a mosquito-derived cell line. Draft genome sequences of this unique isolate, by applying criteria for species delimitation, classified this isolate as a novel strain, proposed as “<i>Rickettsia kedanie</i>.” Further genetic analysis identified conserved virulence factors, and the isolate successfully propagated in mammalian cells, suggesting its ability to cause diseases in humans. The presence of SFG rickettsia in unfed larvae implies potential dual-pathogen carriage and reflects a symbiotic relationship similar to that between the mites and <i>O. tsutsugamushi</i>, indicating possibility of its transovarial transmission from female adults. Furthermore, conserved genomic similarity of the novel isolate to known SFG rickettsia suggests potential multiple hosts, including chiggers and ticks. In the natural environment, ticks, chigger mites, and wild animals may carry new isolates, complicating the infection cycle and increasing the transmission risks to humans. This discovery challenges the conventional association of SFG rickettsia with ticks, emphasizing its implications for research and disease control. However, this study was confined to a particular species of chigger mites and geographic area, underscoring the necessity for additional studies to comprehend the ecological dynamics, host interactions, and health implications linked to this newly identified SFG rickettsia.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141559220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Issue Information – Cover","authors":"","doi":"10.1111/1348-0421.13164","DOIUrl":"https://doi.org/10.1111/1348-0421.13164","url":null,"abstract":"<p><b>Cover photograph</b>: The heatmap of the gut microbiota on the genus level of <i>L</i>. <i>reuteri</i>+LPS group and AKI group. The metabolites heatmap of the two groups. <i>Microbiol Immunol: 68:213-223</i>. Article link here\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1348-0421.13164","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Virological characteristics of the SARS-CoV-2 Omicron EG.5.1 variant","authors":"Shuhei Tsujino,&nbsp;Sayaka Deguchi,&nbsp;Tomo Nomai,&nbsp;Miguel Padilla-Blanco,&nbsp;Arnon Plianchaisuk,&nbsp;Lei Wang,&nbsp;MST Monira Begum,&nbsp;Keiya Uriu,&nbsp;Keita Mizuma,&nbsp;Naganori Nao,&nbsp;Isshu Kojima,&nbsp;Tomoya Tsubo,&nbsp;Jingshu Li,&nbsp;Yasufumi Matsumura,&nbsp;Miki Nagao,&nbsp;Yoshitaka Oda,&nbsp;Masumi Tsuda,&nbsp;Yuki Anraku,&nbsp;Shunsuke Kita,&nbsp;Hisano Yajima,&nbsp;Kaori Sasaki-Tabata,&nbsp;Ziyi Guo,&nbsp;Alfredo A. Hinay Jr.,&nbsp;Kumiko Yoshimatsu,&nbsp;Yuki Yamamoto,&nbsp;Tetsuharu Nagamoto,&nbsp;Hiroyuki Asakura,&nbsp;Mami Nagashima,&nbsp;Kenji Sadamasu,&nbsp;Kazuhisa Yoshimura,&nbsp;Hesham Nasser,&nbsp;Michael Jonathan,&nbsp;Olivia Putri,&nbsp;Yoonjin Kim,&nbsp;Luo Chen,&nbsp;Rigel Suzuki,&nbsp;Tomokazu Tamura,&nbsp;Katsumi Maenaka,&nbsp;Takashi Irie,&nbsp;Keita Matsuno,&nbsp;Shinya Tanaka,&nbsp;Jumpei Ito,&nbsp;Terumasa Ikeda,&nbsp;Kazuo Takayama,&nbsp;Jiri Zahradnik,&nbsp;Takao Hashiguchi,&nbsp;Takasuke Fukuhara,&nbsp;Kei Sato,&nbsp;The Genotype to Phenotype Japan (G2P-Japan) Consortium","doi":"10.1111/1348-0421.13165","DOIUrl":"10.1111/1348-0421.13165","url":null,"abstract":"<p>In middle to late 2023, a sublineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron XBB, EG.5.1 (a progeny of XBB.1.9.2), is spreading rapidly around the world. We performed multiscale investigations, including phylogenetic analysis, epidemic dynamics modeling, infection experiments using pseudoviruses, clinical isolates, and recombinant viruses in cell cultures and experimental animals, and the use of human sera and antiviral compounds, to reveal the virological features of the newly emerging EG.5.1 variant. Our phylogenetic analysis and epidemic dynamics modeling suggested that two hallmark substitutions of EG.5.1, S:F456L and ORF9b:I5T are critical to its increased viral fitness. Experimental investigations on the growth kinetics, sensitivity to clinically available antivirals, fusogenicity, and pathogenicity of EG.5.1 suggested that the virological features of EG.5.1 are comparable to those of XBB.1.5. However, cryo-electron microscopy revealed structural differences between the spike proteins of EG.5.1 and XBB.1.5. We further assessed the impact of ORF9b:I5T on viral features, but it was almost negligible in our experimental setup. Our multiscale investigations provide knowledge for understanding the evolutionary traits of newly emerging pathogenic viruses, including EG.5.1, in the human population.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1348-0421.13165","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathogenicity of genotype 2.1 classical swine fever virus isolated from Japan in 2019 in pigs","authors":"Maiko Yamashita,&nbsp;Shoko Iwamoto,&nbsp;Mariko Ochiai,&nbsp;Atsushi Yamamoto,&nbsp;Kasumi Sudo,&nbsp;Rie Narushima,&nbsp;Takao Nagasaka,&nbsp;Akito Saito,&nbsp;Mami Oba,&nbsp;Tsutomu Omatsu,&nbsp;Tetsuya Mizutani,&nbsp;Kinya Yamamoto","doi":"10.1111/1348-0421.13160","DOIUrl":"10.1111/1348-0421.13160","url":null,"abstract":"<p>Classical swine fever (CSF) re-emerged in Japan in 2018 for the first time in 26 years. The disease has been known to be caused by a moderately pathogenic virus, rather than the highly pathogenic virus that had occurred in the past. However, the underlying pathophysiology remains unknown. This study conducted an experimental challenge on specific pathogen-free (SPF) pigs in a naïve state for 2, 4, and 6 weeks and confirmed the disease state during each period by clinical observation, virus detection, and pathological necropsy. We revealed the pathological changes and distribution of pathogens and virus-specific antibodies at each period after virus challenge. These results were comprehensively analyzed and approximately 70% of the pigs recovered, especially at 4- and 6-week post-virus challenge. This study provides useful information for future countermeasures against CSF by clarifying the pathogenicity outcomes in unvaccinated pigs with moderately pathogenic genotype 2.1 virus.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1348-0421.13160","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor-associated macrophages: The key player in hepatoblastoma microenvironment and the promising therapeutic target","authors":"Ahmad Adawy,&nbsp;Yoshihiro Komohara,&nbsp;Taizo Hibi","doi":"10.1111/1348-0421.13162","DOIUrl":"10.1111/1348-0421.13162","url":null,"abstract":"<p>The tumor microenvironment of hepatoblastoma (HB), the most common pediatric liver tumor, predominantly exhibits a myeloid immune landscape. in which tumor-associated macrophages (TAMs) are considered the core component. The crosstalk between TAMs and HB cells markedly influences tumor behavior. TAM-derived factors are involved in tumor proliferation and vascular invasion. On the other hand, HB cell secretome attracts, stimulates, and reprograms TAMs to be immunosuppressive in favor of tumor invasion, rather than their innate role in combating tumor growth, such crosstalk sometimes forms bidirectional feedback loops, making the tumor more virulent and resistant to routine therapeutics. Consequently, TAMs are the common denominator of most suggested HB immunotherapeutic strategies. Macrophage immune checkpoint inhibitors, macrophage-mediated antibody-dependent cellular phagocytosis, and the novel chimeric antigen receptor macrophage therapy (CAR Mφ) are currently under trial. In this review, we will summarize the significance of TAMs and their potential role as a therapeutic target in HB.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}