Microbiology and Immunology最新文献

{"title":"Inhibition of Targeted Bacterial Growth Using MazF-Expressing Phagemids: A Novel Therapeutic Approach Based on Endoribonuclease Toxin Molecules","authors":"Hana Hasegawa,&nbsp;Tatsuki Miyamoto,&nbsp;Rino Isshiki,&nbsp;Tomoyoshi Kaneko,&nbsp;Kenichi Takasugi,&nbsp;Naohiro Noda,&nbsp;Satoshi Tsuneda","doi":"10.1111/1348-0421.70046","DOIUrl":"10.1111/1348-0421.70046","url":null,"abstract":"<p>The extensive and indiscriminate use of antibiotics, which are intended to halt bacterial growth or eliminate them, has unintentionally given rise to antimicrobial resistance (AMR), which is a critical threat to global health. In the pursuit of alternative solutions, researchers have focused on type II toxin–antitoxin systems prevalent within the bacterial domain. One such promising example is the MazF toxin, which has been demonstrated to cleave RNA at specific sequences. MazF toxins are now recognized as present in a diverse range of bacterial species and exhibit varying cleavage sequence specificities. This diversity offers the potential for controlling bacterial growth by silencing the expression of hundreds of essential genes. In this study, a preliminary screening of five MazF homologs from distinct taxonomic groups was conducted to identify a MazF candidate that can effectively suppress bacterial proliferation. MazFne1, an endoribonuclease toxin originating from <i>Nitrosomonas europaea</i> that specifically targets UGG sequences, emerged as a promising candidate. Building upon this discovery, a phagemid system was engineered to deliver <i>mazFne1</i> and express it in two distinct <i>Escherichia coli</i> strains. This approach successfully inhibited <i>E. coli</i> growth, suggesting a potential strategy for developing therapeutic interventions to combat antibiotic-resistant bacterial infections.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"70 4","pages":"206-213"},"PeriodicalIF":1.8,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13058170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119574","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":"Overexpression of Escherichia coli yaiX Confers Multidrug Resistance and Enhances Virulence in the Silkworm Infection Model","authors":"Kinuka Hongu,&nbsp;Kazuya Ishikawa,&nbsp;Tomoki Kosaki,&nbsp;Shin-Ichi Miyoshi,&nbsp;Kazuyuki Furuta,&nbsp;Chikara Kaito","doi":"10.1111/1348-0421.70049","DOIUrl":"10.1111/1348-0421.70049","url":null,"abstract":"<p>The emergence of bacteria with both antimicrobial resistance and high virulence has become a global health concern, underscoring the urgent need to elucidate the molecular basis underlying these traits. Here, we employed the silkworm (<i>Bombyx mori</i>) infection model, which is suitable for high-throughput screening, together with an <i>Escherichia coli</i> library containing plasmid clones of all genes from strain W3110, to identify genes whose overexpression enhances virulence. We found that overexpression of the uncharacterized protein YaiX promoted bacterial proliferation in silkworms and increased host lethality. Compared with the empty-vector control, the YaiX-overexpressing strain exhibited resistance to multiple antimicrobial agents with diverse mechanisms of action, including <i>β</i>-lactams, tetracyclines, fluoroquinolones, aminoglycosides, cationic surfactants, and hydrogen peroxide. Sequence analysis revealed that amino acids 18–52 of YaiX contain a transferase hexapeptide domain predicted to form a left-handed parallel <i>β</i>-helix. Overexpression of YaiX mutants lacking regions outside this domain conferred ampicillin resistance, whereas deletion of the hexapeptide domain abolished this phenotype. RNA sequencing and GO enrichment analyses further indicated that YaiX overexpression altered the expression of genes encoding RNA-binding proteins and porins. These findings suggest that YaiX overexpression, through its hexapeptide domain, modulates gene expression and contributes to both multidrug resistance and enhanced virulence in <i>E. coli</i>.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"70 4","pages":"193-205"},"PeriodicalIF":1.8,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13058169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147284423","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":"Synergistic Activation of NO and Cytokine Production by TLR3 With TLR5 or TLR7 Agonists in RAW 264.7 Cells","authors":"Thu-Dung Doan,&nbsp;Haroon Afzal,&nbsp;Asad Murtaza,&nbsp;Kamonpun Chuekwon,&nbsp;Li-Ting Cheng","doi":"10.1111/1348-0421.70045","DOIUrl":"10.1111/1348-0421.70045","url":null,"abstract":"<div>\u0000 \u0000 <p>Macrophages are key components of the innate immune system, recognizing pathogen-associated molecular patterns (PAMPs) via Toll-like receptors (TLRs) to initiate immune responses. This study investigated the individual and combinatorial effects of TLR3 Poly(I:C), TLR5 (Flagellin), and TLR7 (Imiquimod) ligands on nitric oxide (NO) production and pro-inflammatory cytokine expression in RAW 264.7 mouse macrophage cells. Our results demonstrate that all three individual TLR agonists induced NO production and cytokine expression. Notably, co-stimulation with Poly(I:C) and imiquimod led to a significant synergistic enhancement of NO production, particularly at lower concentrations. A robust upregulation was observed in key Th1-type (IL-12p40, IFN-γ, TNF-α) and Th2-type (IL-6) cytokines. The optimal synergistic response for cytokine induction was observed with a 0.1 µg/mL Poly(I:C) and 1 µg/mL imiquimod combination. These findings highlight a potent crosstalk between TRIF-dependent (TLR3) and MyD88-dependent (TLR7, TLR5) signaling pathways, leading to amplified immune activation. Our study highlights the potential of synergistic TLR ligand combinations as powerful immunomodulators, offering promising avenues for the rational design of more effective vaccine adjuvants and innovative strategies in cancer immunotherapy.</p></div>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"70 4","pages":"232-240"},"PeriodicalIF":1.8,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146150391","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"70 5","pages":"261-267"},"PeriodicalIF":1.8,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148093641","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"70 5","pages":"280-284"},"PeriodicalIF":1.8,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148087980","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"70 5","pages":"285-289"},"PeriodicalIF":1.8,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148070918","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":"Microbiota in Green Tea Beverages Remaining in Plastic Bottles After Direct Drinking","authors":"Miho Kawachi,&nbsp;Anna Wakui,&nbsp;Manami Imai,&nbsp;Mirai Sekiguchi,&nbsp;Haruna Sato,&nbsp;Yuki Kato,&nbsp;Rika Okabe,&nbsp;Takashi Abe,&nbsp;Nanase Takahashi,&nbsp;Nagara Kaku,&nbsp;Misato Miyazawa,&nbsp;Aya Sato,&nbsp;Yuka Naruse,&nbsp;Nanami Kubo,&nbsp;Ayaka Misumi,&nbsp;Hiroto Sano,&nbsp;Yuki Abiko,&nbsp;Jumpei Washio,&nbsp;Kaori Tanaka,&nbsp;Nobuhiro Takahashi,&nbsp;Takuichi Sato","doi":"10.1111/1348-0421.70041","DOIUrl":"10.1111/1348-0421.70041","url":null,"abstract":"<div>\u0000 \u0000 <p>This study compared bacterial counts and composition in plastic-bottled green tea beverages immediately after direct drinking and after storage at 37°C for 1 day. Immediately after drinking, (1.9 ± 1.6) × 10³ and (4.5 ± 3.9) × 10³ colony forming units (CFU)/mL were recovered from standard green tea and strong green tea, respectively. After 1 day of storage, (1.3 ± 1.5) × 10⁴ and (1.6 ± 3.1) × 10³ CFU/mL were recovered from standard green tea and strong green tea, respectively. Following storage, <i>Lacticaseibacillus</i> spp., <i>Streptococcus</i>, and <i>Veillonella</i> were isolated from both beverages.</p></div>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"70 3","pages":"182-188"},"PeriodicalIF":1.8,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003784","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":"10.1111/1348-0421.70050","DOIUrl":"https://doi.org/10.1111/1348-0421.70050","url":null,"abstract":"<p><b>Cover photograph</b>: Morphological features were used to identify the isolates as belonging to the genus 546 Fonsecaea, in accordance with established micromorphological criteria. <i>Microbiol Immunol: 70:139-147.</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":"70 3","pages":"i-ii"},"PeriodicalIF":1.8,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1348-0421.70050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147563544","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":"Strain Traits of Intracranially Administered L-Type Bovine Spongiform Encephalopathy Prions Are not Significantly Modified During Intraspecies Transmission in Cynomolgus Monkeys","authors":"Ken'ichi Hagiwara,&nbsp;Hiroaki Shibata,&nbsp;Minoru Tobiume,&nbsp;Yuko Sato,&nbsp;Keiko Ohto,&nbsp;Sachi Okabayashi,&nbsp;Nozomi Nakano,&nbsp;Motohiro Horiuchi,&nbsp;Fumiko Ono","doi":"10.1111/1348-0421.70040","DOIUrl":"10.1111/1348-0421.70040","url":null,"abstract":"<p>Among the three prion strains of bovine spongiform encephalopathy (BSE), classical BSE (C-BSE) prions are known causative agents of variant Creutzfeldt–Jakob disease. By contrast, human infections with L-type (L-) or H-type (H-) BSE prions have not been reported. Nonetheless, the zoonotic potential of L-BSE prions is supported by their successful primary transmission from cattle to cynomolgus macaque (<i>Macaca fascicularis</i>) monkeys via intracranial challenge. To assess whether the defining strain traits of L-BSE prions remain stable following secondary intraspecies transmission, we prepared brain homogenates from a diseased macaque that had previously undergone primary transmission of L-BSE prions, and intracranially administered them into two naïve macaques. Both animals succumbed to the disease within humane endpoints comparable to those observed in the primary transmission. Histopathological and immunohistochemical analyses of brain tissues showed no significant changes relative to primary transmission, including severe vacuolation and fine synaptic distribution of disease-associated forms of prion protein (PrP^Sc) in the cerebrum, and sparse PrP^Sc plaques in the cerebellum. In bioassays using C57BL/6 J mice, cattle-derived L-BSE prions and those passaged once or twice in macaques failed to transmit to mice, whereas cattle-derived C-BSE prions and their macaque-passaged counterparts were transmissible. These findings refine our understanding of L-BSE pathogenesis and confirm the stability of L-BSE prions following intracranial transmission in a nonhuman primate model.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"70 3","pages":"166-174"},"PeriodicalIF":1.8,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12963689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146003726","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":"Therapeutic Efficacy of the Supersulfide Donor NAC-S2 in Influenza Virus Pneumonia via Suppression of Excessive Inflammatory Responses","authors":"Foysal Hossen,&nbsp;Takahisa Kouwaki,&nbsp;Yukio Fujiwara,&nbsp;Hiroyasu Tsutsuki,&nbsp;Tianli Zhang,&nbsp;Chunyu Guo,&nbsp;Azizur Rahman,&nbsp;Yoshihiro Komohara,&nbsp;Hiroyuki Oshiumi,&nbsp;Tomohiro Sawa","doi":"10.1111/1348-0421.70039","DOIUrl":"10.1111/1348-0421.70039","url":null,"abstract":"<p>Influenza pneumonia is characterized by excessive inflammatory responses that contribute to severe lung injury and mortality. Supersulfides, endogenously produced cysteine-derived persulfides and polysulfides, exert potent antioxidant, anti-ferroptotic, and anti-inflammatory activities; however, their therapeutic potential after disease onset remains unclear. Here, we investigated the efficacy of <i>N</i>-acetylcysteine tetrasulfide (NAC-S2), a highly water-soluble and cell-permeable supersulfide donor, in a mouse model of influenza A virus (IAV)-induced pneumonia. Subcutaneous administration of NAC-S2 rapidly elevated systemic levels of cysteine- and glutathione-derived supersulfides. In therapeutic treatment starting 2 days post-infection, when body weight loss and clinical signs had already developed, NAC-S2 significantly improved survival and mitigated body weight loss compared with vehicle and oxidized NAC controls. Metabolomic analysis revealed that influenza virus infection depleted lung glutathione persulfide (GSSH), while NAC-S2 effectively restored tissue GSSH levels. NAC-S2 treatment markedly reduced pulmonary interleukin (IL)−1β and IL-6 production without affecting viral load or Type-I interferon responses. Furthermore, NAC-S2 suppressed NLRP3 inflammasome activation and gasdermin D expression, leading to decreased infiltration of CD3⁺ T cells and myeloperoxidase-positive neutrophils. Histopathological analyses confirmed that NAC-S2 ameliorated epithelial injury, interstitial edema, and hemorrhage in infected lungs. Collectively, our findings demonstrate that NAC-S2 exerts therapeutic benefit even after the onset of severe influenza pneumonia, primarily by replenishing supersulfides and alleviating excessive inflammatory responses. Supersulfide donors represent a promising class of adjunctive therapeutics for severe viral pneumonia.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"70 3","pages":"148-159"},"PeriodicalIF":1.8,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12963701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146011290","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}