Human adenovirus type 55 (HAdV-55), formerly designated as HAdV-11a, is a notable recombinant pathogen linked to severe respiratory infections. Since its reclassification as HAdV-55 in 2010, numerous outbreaks of pneumonia associated with it have been documented over the past decade. We conducted a systematic review of 111 peer-reviewed articles from PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) spanning the 60 years (1965-2024). Furthermore, we performed phylogenetic analysis on 87 complete HAdV-55 genomes available in GenBank. Bayesian methods were employed to estimate the temporal evolutionary dynamics of HAdV-55. A total of 15,245 HAdV-55 cases were identified, including 3,790 pneumonia cases (24.86%) and 33 fatalities (case fatality rate: 0.22%), of which 21 (63.63%) were male and the remainder unspecified. Military recruits comprised 79.06% of the cases (12,039/15,245), with adults (95.39%) and males (97.61%) predominantly affected. Asia accounted for the majority of cases (15,060, 98.79%), primarily in China (89.90%), followed by North America (0.98%). The infections caused by HAdV-55 are associated with respiratory (87.27%), gastrointestinal (2.71%), ocular (0.30%), and mental (0.07%) disorders. Phylogenetic analysis identified four variants: HAdV-55a through HAdV-55d, with HAdV-55d emerging as the dominant circulating strain since 2006. Additionally, the E3 region harbors distinct amino acid substitutions correlated with specific countries, suggesting evolution for immune evasion. Bayesian evolutionary analysis estimated the most recent common ancestor (tMRCA) originated in 1929 (95% HPD: 1890-1967). This study underscores the high prevalence of HAdV-55 among adults and males, particularly in China, highlighting the urgent necessity for antiviral therapeutics and vaccines.
人类腺病毒55型（HAdV-55），以前被命名为HAdV-11a，是一种与严重呼吸道感染相关的显著重组病原体。自2010年将其重新分类为HAdV-55以来，在过去十年中记录了许多与之相关的肺炎暴发。我们对来自PubMed、Web of Science和中国知网（CNKI） 60年间（1965-2024）的111篇同行评议文章进行了系统综述。此外，我们对GenBank中87个HAdV-55全基因组进行了系统发育分析。采用贝叶斯方法估计HAdV-55的时间演化动态。共发现15245例HAdV-55病例，包括3790例肺炎病例（24.86%）和33例死亡病例（病死率：0.22%），其中21例（63.63%）为男性，其余病例不明。新兵占79.06%(12039 / 15245)，以成人（95.39%）和男性（97.61%）为主。亚洲占大多数病例（15060例，98.79%），主要在中国（89.90%），其次是北美（0.98%）。HAdV-55引起的感染与呼吸道（87.27%）、胃肠道（2.71%）、眼部（0.30%）和精神（0.07%）疾病相关。系统发育分析确定了四种变体：HAdV-55a至HAdV-55d，自2006年以来，HAdV-55d成为主要的流行菌株。此外，E3区域含有与特定国家相关的独特氨基酸取代，表明免疫逃避的进化。贝叶斯进化分析估计最近的共同祖先（tMRCA）起源于1929年（95% HPD: 1890-1967）。这项研究强调了HAdV-55在成人和男性中的高患病率，特别是在中国，强调了抗病毒治疗和疫苗的迫切需要。
{"title":"High Pathogenicity of Human Adenovirus Type 55 in Adult Males: A Meta-Analysis and Phylogenetic Study of HAdV-55 Epidemics Worldwide Over the Past Six Decades.","authors":"Wenjian Luo,Weimin Guo,Yiqiang Li,Cheng Zhao,Zhijun Weng,Biyan Duan,Jiangtao Wu,Xia Yu,Zhiwei Chen,Donald Seto,James Chodosh,Weifeng Liang,Junxian Ou,Qiwei Zhang","doi":"10.1080/22221751.2026.2648885","DOIUrl":"https://doi.org/10.1080/22221751.2026.2648885","url":null,"abstract":"Human adenovirus type 55 (HAdV-55), formerly designated as HAdV-11a, is a notable recombinant pathogen linked to severe respiratory infections. Since its reclassification as HAdV-55 in 2010, numerous outbreaks of pneumonia associated with it have been documented over the past decade. We conducted a systematic review of 111 peer-reviewed articles from PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) spanning the 60 years (1965-2024). Furthermore, we performed phylogenetic analysis on 87 complete HAdV-55 genomes available in GenBank. Bayesian methods were employed to estimate the temporal evolutionary dynamics of HAdV-55. A total of 15,245 HAdV-55 cases were identified, including 3,790 pneumonia cases (24.86%) and 33 fatalities (case fatality rate: 0.22%), of which 21 (63.63%) were male and the remainder unspecified. Military recruits comprised 79.06% of the cases (12,039/15,245), with adults (95.39%) and males (97.61%) predominantly affected. Asia accounted for the majority of cases (15,060, 98.79%), primarily in China (89.90%), followed by North America (0.98%). The infections caused by HAdV-55 are associated with respiratory (87.27%), gastrointestinal (2.71%), ocular (0.30%), and mental (0.07%) disorders. Phylogenetic analysis identified four variants: HAdV-55a through HAdV-55d, with HAdV-55d emerging as the dominant circulating strain since 2006. Additionally, the E3 region harbors distinct amino acid substitutions correlated with specific countries, suggesting evolution for immune evasion. Bayesian evolutionary analysis estimated the most recent common ancestor (tMRCA) originated in 1929 (95% HPD: 1890-1967). This study underscores the high prevalence of HAdV-55 among adults and males, particularly in China, highlighting the urgent necessity for antiviral therapeutics and vaccines.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"57 1","pages":"2648885"},"PeriodicalIF":13.2,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147483457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a difficult-to-treat pathogen. Phages recovered by a "stepwise" approach may constitute a cocktail able to prolong retardation of bacterial regrowth. We stepwise recovered three lytic phages (namely P04, P40, and P49) from different families against ST11-KL64 CRKP and created a cocktail that restrained CRKP growth for 15 h. Phage P04 recognized bacterial capsular polysaccharide (CPS). P04/P40-resistant mutants lost the large fragments containing CPS gene due to homologous recombination between two insertion sequences. Through gene cloning and complementation experiments, CPS and lipopolysaccharide (LPS) quantification, and untargeted lipid metabolism assays, deletion of the ugd/wbgU genes alters lipid A modification and outer membrane environment. This change affects the accessibility of an unidentified membrane protein or lipid A itself, which serves as the receptor for P40. P49 recognized bacterial transmembrane protein involved in vitamin B12 transportation. Synergistic antibacterial activity was observed because the three phages recognize different receptors. Notably, P49 also lysed Salmonella enterica, Escherichia coli, Enterobacter ludwigii, and Kluyvera tianfuensis, suggesting new receptors would be exposed when the synthesis of CPS was inhibited, thereby allowing efficient attack by phages originally targeting other species (the 'close-one-door-but-open-another' phenomenon). The conserved structure of BtuB provides a molecular basis for the rare cross-genus activity of P49. Insertion sequences provide a generalized anti-phage defense in encapsulated bacteria. Our findings provide critical insights into the versatile mechanisms underpinning bacteria-phages interactions. Specifically, the collateral susceptibility to phages targeting other bacterial species may provide a novel and highly promising approach for creating clinically viable phage cocktails.
{"title":"Stepwise phage resistance and collateral phage susceptibility in Klebsiella pneumoniae.","authors":"Xin Yin,Yu Feng,Huan Luo,Qingqing Fang,Jing Yu,Alan McNally,Zhiyong Zong","doi":"10.1080/22221751.2026.2648890","DOIUrl":"https://doi.org/10.1080/22221751.2026.2648890","url":null,"abstract":"Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a difficult-to-treat pathogen. Phages recovered by a \"stepwise\" approach may constitute a cocktail able to prolong retardation of bacterial regrowth. We stepwise recovered three lytic phages (namely P04, P40, and P49) from different families against ST11-KL64 CRKP and created a cocktail that restrained CRKP growth for 15 h. Phage P04 recognized bacterial capsular polysaccharide (CPS). P04/P40-resistant mutants lost the large fragments containing CPS gene due to homologous recombination between two insertion sequences. Through gene cloning and complementation experiments, CPS and lipopolysaccharide (LPS) quantification, and untargeted lipid metabolism assays, deletion of the ugd/wbgU genes alters lipid A modification and outer membrane environment. This change affects the accessibility of an unidentified membrane protein or lipid A itself, which serves as the receptor for P40. P49 recognized bacterial transmembrane protein involved in vitamin B12 transportation. Synergistic antibacterial activity was observed because the three phages recognize different receptors. Notably, P49 also lysed Salmonella enterica, Escherichia coli, Enterobacter ludwigii, and Kluyvera tianfuensis, suggesting new receptors would be exposed when the synthesis of CPS was inhibited, thereby allowing efficient attack by phages originally targeting other species (the 'close-one-door-but-open-another' phenomenon). The conserved structure of BtuB provides a molecular basis for the rare cross-genus activity of P49. Insertion sequences provide a generalized anti-phage defense in encapsulated bacteria. Our findings provide critical insights into the versatile mechanisms underpinning bacteria-phages interactions. Specifically, the collateral susceptibility to phages targeting other bacterial species may provide a novel and highly promising approach for creating clinically viable phage cocktails.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"6 1","pages":"2648890"},"PeriodicalIF":13.2,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147478827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-17DOI: 10.1080/22221751.2026.2637283
Hongyu Wang,Yan O Wang,Guanmin Yuan,Dan Li,Yutong Chen,Yan A Wang,Quanlin Xue,Jianpeng Cai,Yuhan Sun,Jingjing Zhao,Yulei Sun,Binhuang Sun,Wei Guo,Xiaokun Liu,Hongyan Liu,Jingwen Ai,Wenhong Zhang
Whether latent brucellosis exists prior to symptom onset and predisposes individuals to active disease remains to be determined. We established a novel ELISpot method for brucellosis (B-SPOT) based on host-specific immune. Diagnostic efficacy was evaluated in a testing cohort comprising brucellosis and non-brucellosis participants. A large-scale screening, using serum agglutination test (SAT) and B-SPOT for latent brucellosis, was later performed in Kangping, a brucellosis-endemic area in northern China, followed by a 24-month prospective cohort study to observe the natural development of latent brucellosis without any intervention. Among 41 brucellosis and 57 non-brucellosis participants, the sensitivity of B-SPOT for brucellosis was 95.1%, and the specificity was 98.2%, compared to the combination of blood culture and SAT. 2459 residents were screened, and the prevalence of latent brucellosis was 3.3% (81/2459). Among 63 latent brucellosis cases successfully followed, 33.3% (21/63) progressed to acute brucellosis within 2 years, while none in the control group progressed(p < 0.001). 16/21 (76.2%) progressed within the first six months, and 14/21 (66.7%) presented with joint pain as their initial symptom. B-SPOT (10.94[95%CI 2.48-48.33, p = 0.002]) outperformed SAT (3.04[95%CI 1.14-8.01, p = 0.026]) in predicting the progression of latent brucellosis. Latent brucellosis accounts for 3.3% in the endemic area, among whom 33.3% progressed to acute brucellosis within two years. The first six months are a critical window, and joint pain is the primary initial symptom. B-SPOT demonstrates high diagnostic efficacy for brucellosis disease activity and can better predict the progression of latent brucellosis.
潜伏布鲁氏菌病在症状出现之前是否存在，是否使个体易患活动性疾病仍有待确定。建立了一种新的基于宿主特异性免疫的布鲁氏菌病（B-SPOT） ELISpot检测方法。在包括布鲁氏菌病患者和非布鲁氏菌病患者的测试队列中评估诊断效果。随后，在中国北方布氏菌病流行地区康平，采用血清凝集试验（SAT）和B-SPOT对潜伏性布氏菌病进行了大规模筛查，随后进行了为期24个月的前瞻性队列研究，在没有任何干预的情况下观察潜伏性布氏菌病的自然发展。在41名布鲁氏菌病患者和57名非布鲁氏菌病患者中，与血培养和SAT联合检测相比，B-SPOT检测布鲁氏菌病的敏感性为95.1%，特异性为98.2%。共筛查2459名居民，潜伏布鲁氏菌病患病率为3.3%（81/2459）。成功随访的63例潜伏性布鲁氏菌病患者中，33.3%（21/63）在2年内进展为急性布鲁氏菌病，对照组无进展（p < 0.001）。16/21（76.2%）在前6个月内进展，14/21（66.7%）以关节疼痛为首发症状。B-SPOT （10.94[95%CI 2.48 ~ 48.33, p = 0.002]）在预测潜伏布鲁氏菌病进展方面优于SAT （3.04[95%CI 1.14 ~ 8.01, p = 0.026]）。潜伏性布鲁氏菌病占流行地区的3.3%，其中33.3%在2年内发展为急性布鲁氏菌病。前六个月是一个关键的窗口期，关节疼痛是主要的初始症状。B-SPOT对布鲁氏菌病的活动性具有较高的诊断效能，能较好地预测潜伏性布鲁氏菌病的进展。
{"title":"Natural history of latent brucellosis and diagnostic performance of B-SPOT: a 24-month prospective cohort study based on large-scale screening in northern China.","authors":"Hongyu Wang,Yan O Wang,Guanmin Yuan,Dan Li,Yutong Chen,Yan A Wang,Quanlin Xue,Jianpeng Cai,Yuhan Sun,Jingjing Zhao,Yulei Sun,Binhuang Sun,Wei Guo,Xiaokun Liu,Hongyan Liu,Jingwen Ai,Wenhong Zhang","doi":"10.1080/22221751.2026.2637283","DOIUrl":"https://doi.org/10.1080/22221751.2026.2637283","url":null,"abstract":"Whether latent brucellosis exists prior to symptom onset and predisposes individuals to active disease remains to be determined. We established a novel ELISpot method for brucellosis (B-SPOT) based on host-specific immune. Diagnostic efficacy was evaluated in a testing cohort comprising brucellosis and non-brucellosis participants. A large-scale screening, using serum agglutination test (SAT) and B-SPOT for latent brucellosis, was later performed in Kangping, a brucellosis-endemic area in northern China, followed by a 24-month prospective cohort study to observe the natural development of latent brucellosis without any intervention. Among 41 brucellosis and 57 non-brucellosis participants, the sensitivity of B-SPOT for brucellosis was 95.1%, and the specificity was 98.2%, compared to the combination of blood culture and SAT. 2459 residents were screened, and the prevalence of latent brucellosis was 3.3% (81/2459). Among 63 latent brucellosis cases successfully followed, 33.3% (21/63) progressed to acute brucellosis within 2 years, while none in the control group progressed(p < 0.001). 16/21 (76.2%) progressed within the first six months, and 14/21 (66.7%) presented with joint pain as their initial symptom. B-SPOT (10.94[95%CI 2.48-48.33, p = 0.002]) outperformed SAT (3.04[95%CI 1.14-8.01, p = 0.026]) in predicting the progression of latent brucellosis. Latent brucellosis accounts for 3.3% in the endemic area, among whom 33.3% progressed to acute brucellosis within two years. The first six months are a critical window, and joint pain is the primary initial symptom. B-SPOT demonstrates high diagnostic efficacy for brucellosis disease activity and can better predict the progression of latent brucellosis.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"7 1","pages":"2637283"},"PeriodicalIF":13.2,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147471693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Clostridioides difficile (C. difficile) ribotype 027 (RT027) has caused severe outbreaks in North America and Europe over the past 20 years. However, RT027 infections are rare in Asia, particularly in China, with limited severe cases. To clarify its molecular and phenotypic features, we investigated 11 RT027 isolates collected from Shandong, China. Whole-genome sequencing, comparative transcriptomics, CRISPR-Cas analysis, and pan-genome profiling were combined with phenotypic assays of toxin production, sporulation, antimicrobial resistance, and motility. Evolutionary analysis demonstrated that isolates from China clearly diverged from the FQR2 lineage and were phylogenetically closer to FQR1, forming a distinct sublineage. All isolates from Shandong, China encoded a complete tcd and cdt locus and harboured rifamycin and aminoglycoside resistance genes. However, transcriptomic profiling demonstrated significantly reduced expression of binary toxin genes (cdtAB, cdtR), decreased spo0A transcription, and downregulation of flagellar pathways. Phenotypic assays confirmed impaired sporulation, motility and cytotoxicity, while TcdB production and adhesion was comparable to reference strains. CRISPR-Cas elements were conserved but showed reduced transcriptional activity, suggesting diminished host-pathogen interactions. The pan-genome revealed high genomic conservation, consistent with limited functional diversity. Together, these data indicate that RT027 isolates circulating in China possess unique evolutionary trajectories and attenuated virulence traits, helping to explain the rarity of severe RT027 infections in Asia. These findings provide important insights into the regional epidemiology of C. difficile and inform strategies for diagnosis, treatment, and prevention.
{"title":"Genomic and phenotypic insight into Clostridioides difficile RT027 isolates from China reveals diverse virulence associated with clinical symptoms.","authors":"Wenjia Wang,Shan Lin,Yun Luo,Chunhong Shao,Qikai Shi,Jing Shao,Yu Chen,Hui Hu,Shuangshuang Wan,Xiaojun Song,Dazhi Jin,Yan Jin","doi":"10.1080/22221751.2026.2637287","DOIUrl":"https://doi.org/10.1080/22221751.2026.2637287","url":null,"abstract":"Clostridioides difficile (C. difficile) ribotype 027 (RT027) has caused severe outbreaks in North America and Europe over the past 20 years. However, RT027 infections are rare in Asia, particularly in China, with limited severe cases. To clarify its molecular and phenotypic features, we investigated 11 RT027 isolates collected from Shandong, China. Whole-genome sequencing, comparative transcriptomics, CRISPR-Cas analysis, and pan-genome profiling were combined with phenotypic assays of toxin production, sporulation, antimicrobial resistance, and motility. Evolutionary analysis demonstrated that isolates from China clearly diverged from the FQR2 lineage and were phylogenetically closer to FQR1, forming a distinct sublineage. All isolates from Shandong, China encoded a complete tcd and cdt locus and harboured rifamycin and aminoglycoside resistance genes. However, transcriptomic profiling demonstrated significantly reduced expression of binary toxin genes (cdtAB, cdtR), decreased spo0A transcription, and downregulation of flagellar pathways. Phenotypic assays confirmed impaired sporulation, motility and cytotoxicity, while TcdB production and adhesion was comparable to reference strains. CRISPR-Cas elements were conserved but showed reduced transcriptional activity, suggesting diminished host-pathogen interactions. The pan-genome revealed high genomic conservation, consistent with limited functional diversity. Together, these data indicate that RT027 isolates circulating in China possess unique evolutionary trajectories and attenuated virulence traits, helping to explain the rarity of severe RT027 infections in Asia. These findings provide important insights into the regional epidemiology of C. difficile and inform strategies for diagnosis, treatment, and prevention.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"190 1","pages":"2637287"},"PeriodicalIF":13.2,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147471804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-16DOI: 10.1080/22221751.2026.2627078
Yinggai Song, Margriet W. J. Hokken, Jan Zoll, Hanka Venselaar, Paul E. Verweij, Willem J. G. Melchers, Johanna Rhodes
{"title":"Accelerated mutator phenotype in a clinical Aspergillus fumigatus isolate contributes to adaptive evolution","authors":"Yinggai Song, Margriet W. J. Hokken, Jan Zoll, Hanka Venselaar, Paul E. Verweij, Willem J. G. Melchers, Johanna Rhodes","doi":"10.1080/22221751.2026.2627078","DOIUrl":"https://doi.org/10.1080/22221751.2026.2627078","url":null,"abstract":"","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"20 1","pages":""},"PeriodicalIF":13.2,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147465504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The global rise of multidrug-resistant Klebsiella pneumoniae underscores the urgent need for alternative therapeutic strategies. Bacteriophage-derived depolymerases have emerged as promising antimicrobial factors, selectively degrading bacterial capsules and impairing key pathogenic traits. We characterize a novel depolymerase, PRA33gp45, associated with the structural protein of bacteriophage vB_KpnP_PRA33. Bioinformatic structural analyses predicted endo-N-acetyl neuraminidase-like activity and canonical depolymerase domain architecture. The recombinant PRA33gp45 specifically hydrolysed capsular polysaccharides (CPS) of K27-serotype K. pneumoniae and produced characteristic halo zones on bacterial lawns, confirming its enzymatic activity. Capsule staining demonstrated rapid and progressive capsule degradation within 120 minutes of treatment. PRA33gp45 significantly inhibited biofilm formation, disrupted mature biofilms, and altered biofilm architecture as visualized by confocal microscopy. Depolymerase pre-treatment markedly reduced K. pneumoniae survival within A549 human lung epithelial cells, without exhibiting any cytotoxic effect and sensitized bacteria to complement-mediated killing in human serum. Finally, PRA33gp45 treatment of K. pneumoniae lowers morbidity and mortality in the Galleria mellonella larvae model. Collectively, these findings identify PRA33gp45 as a novel and highly specific depolymerase that diminishes K. pneumoniae virulence by targeting its protective capsule, impairing persistence as biofilm, and enhancing innate immune clearance. Its safety and efficacy suggest potential as an antimicrobial or adjuvant therapeutic agent against K27-type K. pneumoniae infections, particularly in the context of multidrug resistance and emerging pathogens.
全球耐多药肺炎克雷伯菌的增加强调了迫切需要替代治疗策略。噬菌体衍生的解聚合酶已成为有前途的抗菌因子，选择性地降解细菌胶囊和损害关键的致病性状。我们鉴定了一种新的解聚合酶PRA33gp45，它与噬菌体vB_KpnP_PRA33的结构蛋白相关。生物信息学结构分析预测内切- n -乙酰基神经氨酸酶样活性和典型解聚合酶结构域结构。重组PRA33gp45特异性水解k27血清型肺炎克雷伯菌的荚膜多糖（CPS），并在细菌草坪上产生特征性的晕带，证实了其酶活性。胶囊染色显示在120分钟内胶囊迅速和渐进降解。共聚焦显微镜显示，PRA33gp45显著抑制生物膜形成，破坏成熟生物膜，改变生物膜结构。解聚合酶预处理显著降低了肺炎克雷伯菌在A549人肺上皮细胞内的存活率，没有表现出任何细胞毒性作用，并使细菌对补体介导的人血清杀伤敏感。最后，PRA33gp45治疗肺炎克雷伯菌降低了mellonella幼虫模型的发病率和死亡率。总的来说，这些发现确定了PRA33gp45是一种新型的、高度特异性的解聚合酶，通过靶向肺炎克雷伯菌的保护胶囊、损害其作为生物膜的持久性和增强先天免疫清除来降低其毒力。它的安全性和有效性表明它有潜力作为抗k27型肺炎克雷伯菌感染的抗菌或辅助治疗剂，特别是在多药耐药和新出现病原体的情况下。
{"title":"Phage-derived depolymerase targeting K27 capsule impairs Klebsiella pneumoniae virulence, biofilm formation, and promotes immune clearance.","authors":"Magdalena Pelka,Weronika Czekala,Agnieszka Kwiatek,Marta Polanska,Barbara Maciejewska,Aleksandra Otwinowska,Piotr Golec,Agnieszka Wyszyńska,Zuzanna Drulis-Kawa,Monika Adamczyk-Popławska","doi":"10.1080/22221751.2026.2645857","DOIUrl":"https://doi.org/10.1080/22221751.2026.2645857","url":null,"abstract":"The global rise of multidrug-resistant Klebsiella pneumoniae underscores the urgent need for alternative therapeutic strategies. Bacteriophage-derived depolymerases have emerged as promising antimicrobial factors, selectively degrading bacterial capsules and impairing key pathogenic traits. We characterize a novel depolymerase, PRA33gp45, associated with the structural protein of bacteriophage vB_KpnP_PRA33. Bioinformatic structural analyses predicted endo-N-acetyl neuraminidase-like activity and canonical depolymerase domain architecture. The recombinant PRA33gp45 specifically hydrolysed capsular polysaccharides (CPS) of K27-serotype K. pneumoniae and produced characteristic halo zones on bacterial lawns, confirming its enzymatic activity. Capsule staining demonstrated rapid and progressive capsule degradation within 120 minutes of treatment. PRA33gp45 significantly inhibited biofilm formation, disrupted mature biofilms, and altered biofilm architecture as visualized by confocal microscopy. Depolymerase pre-treatment markedly reduced K. pneumoniae survival within A549 human lung epithelial cells, without exhibiting any cytotoxic effect and sensitized bacteria to complement-mediated killing in human serum. Finally, PRA33gp45 treatment of K. pneumoniae lowers morbidity and mortality in the Galleria mellonella larvae model. Collectively, these findings identify PRA33gp45 as a novel and highly specific depolymerase that diminishes K. pneumoniae virulence by targeting its protective capsule, impairing persistence as biofilm, and enhancing innate immune clearance. Its safety and efficacy suggest potential as an antimicrobial or adjuvant therapeutic agent against K27-type K. pneumoniae infections, particularly in the context of multidrug resistance and emerging pathogens.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"44 1","pages":"2645857"},"PeriodicalIF":13.2,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147447087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-13DOI: 10.1080/22221751.2026.2645856
Ahmed Kandeil,Pradeep Chopra,Sean D Ray,Balasaheb K Ghotekar,Charlene Ranadheera,Trushar Jeevan,Thomas Fabrizio,Adam Rubrum,Geert-Jan Boons,Stephen Mark Tompkins,Nathalie Bastien,Richard J Webby
Clade 2.3.4.4b A(H5N1) influenza viruses continue to expand their host range and pose increasing public health concerns. A case of severe human infection with genotype D1.1 A(H5N1) with HÀ substitutions was diagnosed in British Columbia. It is important to monitor receptor-binding specificity and antigenicity of emerging variants of circulating influenza A(H5N1) viruses. To evaluate potential human adaptation of this virus, we enriched HA-variant subpopulations and assessed sialic acid receptor usage via glycan microarray, solid-phase assays, and biolayer interferometry. All variants bound exclusively to avian-type sialic acid receptors. The antigenicity of the tested A(H5N1) variants was covered by candidate vaccine viruses.
{"title":"Receptor-binding specificity and antigenic properties of a genotype D1.1 A(H5N1) influenza virus isolated from a human.","authors":"Ahmed Kandeil,Pradeep Chopra,Sean D Ray,Balasaheb K Ghotekar,Charlene Ranadheera,Trushar Jeevan,Thomas Fabrizio,Adam Rubrum,Geert-Jan Boons,Stephen Mark Tompkins,Nathalie Bastien,Richard J Webby","doi":"10.1080/22221751.2026.2645856","DOIUrl":"https://doi.org/10.1080/22221751.2026.2645856","url":null,"abstract":"Clade 2.3.4.4b A(H5N1) influenza viruses continue to expand their host range and pose increasing public health concerns. A case of severe human infection with genotype D1.1 A(H5N1) with HÀ substitutions was diagnosed in British Columbia. It is important to monitor receptor-binding specificity and antigenicity of emerging variants of circulating influenza A(H5N1) viruses. To evaluate potential human adaptation of this virus, we enriched HA-variant subpopulations and assessed sialic acid receptor usage via glycan microarray, solid-phase assays, and biolayer interferometry. All variants bound exclusively to avian-type sialic acid receptors. The antigenicity of the tested A(H5N1) variants was covered by candidate vaccine viruses.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"9 1","pages":"2645856"},"PeriodicalIF":13.2,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147447092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A rickettsial pathogen Ehrlichia chaffeensis causes emerging tick-borne disease called human monocytic ehrlichiosis (HME). E. chaffeensis in ticks expresses a porin OMP-1B, the immunodominant major outer membrane protein, which is required for nutrient uptake across outer membrane of bacteria. We developed an OMP-1B-encoding mRNA-lipid nanoparticle (hereafter OMP-1B mRNA-LNP) vaccine. Immunization of naïve mice with OMP-1B mRNA-LNP showed significant protection against E. chaffeensis infection following challenge with E. chaffeensis-infected tick cells. Following vaccination, increased OMP-1B-specific serum IgG, IgG1, and IgG2a titers, and E. chaffeensis infection-neutralizing antibodies were detected. An ELISpot assay revealed significant increase in OMP-1B-specific IFN-γ-secreting cells in the blood and spleen samples from mice vaccinated with OMP-1B mRNA-LNP. Flow cytometry analysis of spleen samples showed OMP-1B antigen-specific IFN-γ-producing CD4+ and CD8+ T cells and granzyme B-producing cytotoxic CD8+ T cells were significantly increased in the vaccinated mice. Our results demonstrate that an mRNA vaccine targeting OMP-1B conferred protection against E. chaffeensis infection, with significant humoral immune responses including infection-neutralizing antibodies, balanced Th1/Th2 response, and antigen-specific T helper and cytotoxic T cell activation. These data suggest mRNA-LNP approach is a viable strategy for developing efficient anti-rickettsial vaccines.
{"title":"Efficacy and immunological correlates of an mRNA-LNP vaccine for protection against an emerging rickettsial pathogen.","authors":"Mingqun Lin,Stephen Denton,Nan Duan,Naveed Iqbal,Prosper N Boyaka,Garima Dwivedi,Mohamad-Gabriel Alameh,Drew Weissman,Yasuko Rikihisa","doi":"10.1080/22221751.2026.2645860","DOIUrl":"https://doi.org/10.1080/22221751.2026.2645860","url":null,"abstract":"A rickettsial pathogen Ehrlichia chaffeensis causes emerging tick-borne disease called human monocytic ehrlichiosis (HME). E. chaffeensis in ticks expresses a porin OMP-1B, the immunodominant major outer membrane protein, which is required for nutrient uptake across outer membrane of bacteria. We developed an OMP-1B-encoding mRNA-lipid nanoparticle (hereafter OMP-1B mRNA-LNP) vaccine. Immunization of naïve mice with OMP-1B mRNA-LNP showed significant protection against E. chaffeensis infection following challenge with E. chaffeensis-infected tick cells. Following vaccination, increased OMP-1B-specific serum IgG, IgG1, and IgG2a titers, and E. chaffeensis infection-neutralizing antibodies were detected. An ELISpot assay revealed significant increase in OMP-1B-specific IFN-γ-secreting cells in the blood and spleen samples from mice vaccinated with OMP-1B mRNA-LNP. Flow cytometry analysis of spleen samples showed OMP-1B antigen-specific IFN-γ-producing CD4+ and CD8+ T cells and granzyme B-producing cytotoxic CD8+ T cells were significantly increased in the vaccinated mice. Our results demonstrate that an mRNA vaccine targeting OMP-1B conferred protection against E. chaffeensis infection, with significant humoral immune responses including infection-neutralizing antibodies, balanced Th1/Th2 response, and antigen-specific T helper and cytotoxic T cell activation. These data suggest mRNA-LNP approach is a viable strategy for developing efficient anti-rickettsial vaccines.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"7 1","pages":"2645860"},"PeriodicalIF":13.2,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147439263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AbstractMonkeypox virus (MPXV) is a zoonotic pathogen known to be endemic to the Congo basin and West Africa, and which causes characteristic lesions disseminated on all skin surfaces of infected cases. Multiple MPXV outbreaks have been reported in the Central African Republic (CAR), a Congo basin country, at an increased frequency since 2020. The genomic history of these outbreaks in CAR is poorly characterized due to under sampling, with only a recent expansion in the number of sequences from CAR. Here, we report twenty-six new near-complete genomes from six prefectures of CAR, selected to represent outbreaks that occurred in the country between 2019 and 2024. Our analysis shows the sustained homogeneity of genomes in CAR, as all of them belonged to Clade Ia, but with an expansion of sub-lineages and therefore increased MPXV diversity within CAR. We highlight the introduction into CAR of a lineage previously known to occur only in Gabon and Cameroon, as well as the apparent regional clustering of MPXV genomes in CAR. Our analysis reveals limited APOBEC3-mediated activity, which is consistent with recent zoonotic origins and short human-to-human transmission chains observed in CAR. These analyses provide an in-depth view on the genomic diversity of MPXV in the Central African region.
{"title":"Genomic Diversity of Clade Ia Monkeypox Virus in the Central African Republic, 2019-2024.","authors":"Alexander Tendu,Lingjing Mao,Stéphane Descorps-Declère,Benjamin Selekon,Ella Farra,Camille Besombes,Sandra Garba-Ouangole,Huguette Dorine Simo,Délia Doreen Djuicy,Raphäel Mbaïlao,Jean Méthode Moyen,Ernest Kalthan,Pierre Somse,Thomas D'aquin Koyazegbet,Richard Njouom,Sebastian Duchene,Arnaud Fontanet,Gary Wong,Emmanuel Nakouné,Antoine Gessain,Nicolas Berthet","doi":"10.1080/22221751.2026.2645863","DOIUrl":"https://doi.org/10.1080/22221751.2026.2645863","url":null,"abstract":"AbstractMonkeypox virus (MPXV) is a zoonotic pathogen known to be endemic to the Congo basin and West Africa, and which causes characteristic lesions disseminated on all skin surfaces of infected cases. Multiple MPXV outbreaks have been reported in the Central African Republic (CAR), a Congo basin country, at an increased frequency since 2020. The genomic history of these outbreaks in CAR is poorly characterized due to under sampling, with only a recent expansion in the number of sequences from CAR. Here, we report twenty-six new near-complete genomes from six prefectures of CAR, selected to represent outbreaks that occurred in the country between 2019 and 2024. Our analysis shows the sustained homogeneity of genomes in CAR, as all of them belonged to Clade Ia, but with an expansion of sub-lineages and therefore increased MPXV diversity within CAR. We highlight the introduction into CAR of a lineage previously known to occur only in Gabon and Cameroon, as well as the apparent regional clustering of MPXV genomes in CAR. Our analysis reveals limited APOBEC3-mediated activity, which is consistent with recent zoonotic origins and short human-to-human transmission chains observed in CAR. These analyses provide an in-depth view on the genomic diversity of MPXV in the Central African region.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"13 1","pages":"2645863"},"PeriodicalIF":13.2,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147447064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：