{"title":"Rad6 and Bre1 ubiquitin ligase negatively regulate biofilm formation and virulence in Candida glabrata","authors":"Yi-Hang Lee , Li-Hang Hsu , Zi-Heng Yu , Kai-Quan Leong , Hao-Sen Chiang , Ying-Lien Chen","doi":"10.1016/j.jinf.2025.106595","DOIUrl":"10.1016/j.jinf.2025.106595","url":null,"abstract":"<div><h3>Background</h3><div><em>Candida glabrata</em> is an opportunistic human fungal pathogen causing infections due to its innate antifungal drug resistance and ability to adhere to mucocutaneous surfaces. Epigenetic pathways may be important factors in the development of drug resistance. Our previous studies showed that deubiquitination of H2B, regulated by a module comprised of Ubp8, Sgf11, Sgf73, and Sus1, plays important roles in oxidative stress tolerance and biofilm formation of <em>C. glabrata</em>. However, the roles of the Rad6 and Bre1 ligase in regulating the ubiquitination of H2B in <em>C. glabrata</em> remain unclear.</div></div><div><h3>Methods</h3><div>We characterized the functions of Rad6 and Bre1 in <em>C. glabrata</em> by generating deletion mutants (<em>rad6</em>, <em>bre1</em>, and <em>rad6 bre1</em>). We analyzed biofilm formation, gene expression of key adhesins (<em>EPA1</em>, <em>EPA6</em>, <em>EPA20</em>) and protease (<em>YPS4</em>), antifungal drug susceptibility, stress responses, and virulence in a murine model of systemic candidiasis.</div></div><div><h3>Results</h3><div>Deletion of <em>RAD6</em> and <em>BRE1</em> resulted in enhanced biofilm formation, correlating with upregulation of key adhesin genes and the protease gene <em>YPS4</em>. The mutants showed distinct patterns of antifungal drug susceptibility: <em>rad6</em> and <em>rad6 bre1</em> mutants exhibited increased sensitivity to azoles, while <em>bre1</em> mutant showed enhanced resistance to azoles in solid YPD agar plates but no significant difference in liquid RPMI medium. All mutants demonstrated decreased resistance to echinocandins and amphotericin B, associated with altered expression of ergosterol biosynthesis genes (<em>ERG11</em>) and glucan synthase genes (<em>FKS1</em>, <em>FKS2</em>). The mutants also displayed decreased resistance to oxidative and cell wall stresses despite elevated basal expression of antioxidant genes (<em>SOD1</em>, <em>GPX2</em>, <em>CTA1</em>). In a murine model of systemic candidiasis, both <em>rad6</em> and <em>bre1</em> mutants exhibited enhanced virulence compared to the wild type.</div></div><div><h3>Conclusion</h3><div>Rad6 and Bre1 in <em>C. glabrata</em> function as negative regulators of biofilm formation and adhesion, and their related-genes expression, while <em>RAD6</em> deletion also suppresses macrophage ROS production and enhances fungal survival. The enhanced virulence observed in the <em>rad6</em> and <em>bre1</em> mutants is primarily attributed to these combined effects of increased biofilm formation, enhanced adhesion capability, and macrophage immune evasion.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 3","pages":"Article 106595"},"PeriodicalIF":11.9,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144916624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gift Ahimbisibwe , David Greenwood , Katalin Andrea Wilkinson , Joshua Gahir , Hermaleigh Townsley , Murad Miah , Philip Bawumia , Charlotte Chaloner , Dina Levi , Philip Hobson , Andy Riddell , Agnieszka Hobbs , Giulia Dowgier , Rebecca Penn , Theo Sanderson , Phoebe Stevenson-Leggett , Odiesia Daley , James Bazire , Ruth Harvey , Ashley S. Fowler , Emma C. Wall
{"title":"Third exposure to COVID-19 infection or vaccination differentially impacts T cell responses","authors":"Gift Ahimbisibwe , David Greenwood , Katalin Andrea Wilkinson , Joshua Gahir , Hermaleigh Townsley , Murad Miah , Philip Bawumia , Charlotte Chaloner , Dina Levi , Philip Hobson , Andy Riddell , Agnieszka Hobbs , Giulia Dowgier , Rebecca Penn , Theo Sanderson , Phoebe Stevenson-Leggett , Odiesia Daley , James Bazire , Ruth Harvey , Ashley S. Fowler , Emma C. Wall","doi":"10.1016/j.jinf.2025.106598","DOIUrl":"10.1016/j.jinf.2025.106598","url":null,"abstract":"<div><h3>Background</h3><div>In 2021, the rapid rollout of two doses of SARS-CoV-2 vaccines reduced COVID-19 severity and mortality. However, further vaccine doses as a prime-boost schedule were limited, and lifting of public health restrictions by late 2021 frequently led to infection, rather than vaccine, as a third exposure.</div></div><div><h3>Objective</h3><div>To compare how the third exposure through mRNA booster or SARS-CoV-2 infection shapes humoral and cellular immunity following two vaccine doses.</div></div><div><h3>Methods</h3><div>We compared immune responses after the third exposure in healthy adults enrolled in the UCLH-Crick Legacy cohort study (NCT04750356) between those receiving ancestral spike-encoded mRNA booster (vaccine immunity, n = 38) or COVID-19 infection (hybrid immunity, n = 13) following two vaccine doses. Immune profiles were evaluated using live virus neutralization assays, IFN-γ ELISpot, Luminex assay, flow cytometry and mass cytometry.</div></div><div><h3>Results</h3><div>Both total anti-Spike IgG and variant-specific neutralising antibodies were comparable following infection or vaccine as a third exposure. Overall, T cell populations were similar but functionally different. CD8⁺ Effector Memory (TEM) cells in the vaccine group showed higher expression of CD69 and Granzyme B following stimulation with SARS-CoV-2 Spike peptides. In contrast, the hybrid group produced higher levels of innate immune associated cytokines IL-10 and IL-34, as well as the T cell homing chemokine CCL25, after stimulation.</div></div><div><h3>Conclusions</h3><div>While both exposures generated comparable breadth of protection against SARS-CoV-2 variants, our findings suggest that the route of third exposure influences different aspects of the immune response, warranting further investigation into long-term immunity at both systemic and mucosal sites.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 3","pages":"Article 106598"},"PeriodicalIF":11.9,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144911812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Federica Attaianese , Sandra Trapani , Rino Agostiniani , Nicoletta Ambrosino , Giulia Bertolucci , Paolo Biasci , Barbara Castelli , Gloria Colarusso , Giulia Coretti , Carlo Dani , Salvatore Grosso , Ersilia Lucenteforte , Debora Maj , Marco Martini , Gianpaolo Mirri , Maria Moriondo , Vanessa Perone , Diego Peroni , Annalisa Rossetti , Silvia Ricci , Giuseppe Indolfi
{"title":"Effectiveness of a targeted infant RSV immunization strategy (2024–2025): A multicenter matched case-control study in a high-surveillance setting","authors":"Federica Attaianese , Sandra Trapani , Rino Agostiniani , Nicoletta Ambrosino , Giulia Bertolucci , Paolo Biasci , Barbara Castelli , Gloria Colarusso , Giulia Coretti , Carlo Dani , Salvatore Grosso , Ersilia Lucenteforte , Debora Maj , Marco Martini , Gianpaolo Mirri , Maria Moriondo , Vanessa Perone , Diego Peroni , Annalisa Rossetti , Silvia Ricci , Giuseppe Indolfi","doi":"10.1016/j.jinf.2025.106600","DOIUrl":"10.1016/j.jinf.2025.106600","url":null,"abstract":"<div><h3>Background</h3><div>Nirsevimab, a long-acting monoclonal antibody against respiratory syncytial virus (RSV), was recently introduced to prevent infant RSV-related hospitalizations. Although efficacy has been demonstrated in clinical trials, real-world data on targeted immunization strategies remain limited. We aimed to evaluate the effectiveness of nirsevimab in preventing RSV-associated hospitalizations in infants under 12 months, within a seasonal program prioritizing infants born from April onwards.</div></div><div><h3>Methods</h3><div>We conducted a prospective, multicenter, matched case-control study across seven Italian hospitals during the 2024–2025 RSV season. Infants hospitalized with PCR-confirmed RSV bronchiolitis were matched 1:2 by age and date of admission to controls hospitalized for non-respiratory causes. Data were collected via electronic medical records. Immunization effectiveness (IE) was estimated using conditional logistic regression adjusted for sex assigned at birth, gestational age, birth weight, and clinical risk factors. Two pre-specified stratified analyses and a sensitivity analysis using inverse probability of treatment weighting (IPTW) were performed.</div></div><div><h3>Results</h3><div>A total of 138 infants were included (46 cases, 92 controls). Adjusted IE was 89.5% (95% CI: 60.3–97.2%). Stratified analyses yielded similar results among infants born after April 1 (IE: 88.4%, 95% CI: 56.5–96.9%) and those without risk factors (IE: 88.1%, 95% CI: 45.7–97.4%). IPTW analysis confirmed protection (IE: 79.6%, 95% CI: 53.5–91.0%).</div></div><div><h3>Conclusions</h3><div>This study provides real-world evidence supporting the effectiveness of nirsevimab in a targeted seasonal immunization framework. These findings may inform phased implementation strategies and RSV prophylaxis policies in varied healthcare settings.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 3","pages":"Article 106600"},"PeriodicalIF":11.9,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144889370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Boyan Liu , Song Song , Wenlong Liu , Yuqi Hu , Cuiling Wei , Lingyue Zhou , Qi Sun , Wenxin Tian , Rachel Yui Ki Chu , Ian Chi Kei Wong , Ivan Fan Ngai Hung , Eric Yuk Fai Wan , Xue Li , Celine Sze Ling Chui , Esther Wai Yin Chan , Carlos King Ho Wong , Francisco Tsz Tsun Lai
{"title":"Post-COVID-19 multimorbidity incidence by prior vaccination status in people with a pre-existing comorbidity: A population-based cohort study","authors":"Boyan Liu , Song Song , Wenlong Liu , Yuqi Hu , Cuiling Wei , Lingyue Zhou , Qi Sun , Wenxin Tian , Rachel Yui Ki Chu , Ian Chi Kei Wong , Ivan Fan Ngai Hung , Eric Yuk Fai Wan , Xue Li , Celine Sze Ling Chui , Esther Wai Yin Chan , Carlos King Ho Wong , Francisco Tsz Tsun Lai","doi":"10.1016/j.jinf.2025.106597","DOIUrl":"10.1016/j.jinf.2025.106597","url":null,"abstract":"<div><h3>Background</h3><div>Long-term health consequences of COVID-19, particularly among individuals with pre-existing chronic diseases, are not fully understood. This study investigates whether SARS-CoV-2 infection increases the risk of developing multimorbidity (≥2 chronic conditions) and evaluates protective effects of vaccination.</div></div><div><h3>Methods</h3><div>We analyzed territory-wide electronic health records from Hong Kong, linking Hospital Authority data with COVID-19 infection and vaccination records from the Department of Health. A retrospective matched-cohort study was conducted among patients with one pre-existing chronic condition. Participants were stratified into three groups: (1) no documented COVID-19 infection, (2) COVID-19 infection with incomplete vaccination (<3 doses), and (3) COVID-19 infection with full vaccination (≥3 doses). The primary outcome was the incidence of a second chronic condition from a pre-specified list.</div></div><div><h3>Results</h3><div>Among 1,038,175 eligible individuals, 68,975 (6.64%) developed multimorbidity over a median follow-up of 192 days (IQR: 96–313). The non-COVID-19 group (51,288 cases) had an incidence rate of 68.88 per 1000 person-years (95% CI: 68.18–69.37). In contrast, the COVID-19/unvaccinated group (9455 cases) exhibited a significantly higher rate (86.58; 95% CI: 84.85–88.35). The COVID-19/vaccinated group (8232 cases) showed a moderated rate (72.84; 95% CI: 71.27–74.43). Adjusted incidence rate ratios were 1.26 (95% CI: 1.23–1.29) for unvaccinated and 1.08 (95% CI: 1.05–1.11) for vaccinated individuals compared to the non-COVID-19 group. Results remained consistent across age, sex, and comorbidity subgroups.</div></div><div><h3>Interpretation</h3><div>COVID-19 infection is associated with an increased risk of multimorbidity in patients with pre-existing conditions. Full vaccination attenuates this risk substantially, highlighting its critical role in mitigating post-infection complications.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 3","pages":"Article 106597"},"PeriodicalIF":11.9,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144892175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wolfgang Bauer , Noa Galtung , Peter Geserick , Katharina Friedrich , Marcus Weber , Rajan Somasundaram , Eva Diehl-Wiesenecker , Kai Kappert
{"title":"Pentraxin-3, MyD88, GLP-1, and PD-L1: Performance assessment and composite algorithmic analysis for sepsis identification","authors":"Wolfgang Bauer , Noa Galtung , Peter Geserick , Katharina Friedrich , Marcus Weber , Rajan Somasundaram , Eva Diehl-Wiesenecker , Kai Kappert","doi":"10.1016/j.jinf.2025.106599","DOIUrl":"10.1016/j.jinf.2025.106599","url":null,"abstract":"<div><h3>Objectives</h3><div>Accurate diagnosis of sepsis is needed to initiate life-saving treatment decisions. Biomarkers capable of identifying both acute infection and sepsis are required to assist clinicians.</div></div><div><h3>Methods</h3><div>A real-life heterogeneous cohort of 388 patients with suspected acute infections was recruited at presentation to the ED. Nine emerging host-response biomarkers (MyD88, MMP-8, leptin, ENA-78, fractalkine, PD- L1, pentraxin-3, TRAIL, and GLP-1) were quantified using a multiparameter assay. We performed AUROC analysis for the endpoints bacterial infection, sepsis, and 30-day mortality. We further assessed diagnostic performance when combining these biomarkers using a machine learning algorithm.</div></div><div><h3>Results</h3><div>Particularly, MyD88, PD-L1, and pentraxin-3 presented high AUROCs for the endpoints bacterial infection (≥0.87), sepsis (≥0.81), and 30-day mortality (≥0.71). Seven out of the nine investigated biomarkers showed statistically significant discrimination for all three endpoints. A combined algorithm via the XGBoost model using pentraxin-3, MyD88, and GLP-1 was used for sepsis prediction, with an AUROC of 0.89, higher than clinical assessment via NEWS-2 (0.83) or procalcitonin (0.81).</div></div><div><h3>Conclusion</h3><div>Pentraxin-3, MyD88, GLP-1, and PD-L1 are a promising complementary set of biomarkers for risk assessment and stratification. When a trained multiparameter classifier is used, the combination of biomarkers results in a valid tool for sepsis diagnosis.</div></div><div><h3>Trial registration</h3><div>DRKS00020521, DRKS00017395</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 3","pages":"Article 106599"},"PeriodicalIF":11.9,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144889369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prevalence and transmission of influenza A (H6) viruses pose a potential threat to public health","authors":"Xingdong Song , Xiaohong Hou , Yue Li, Ruihua Zhang, Yu Meng, Yanli Zhu, Liangmeng Wei, Shijin Jiang","doi":"10.1016/j.jinf.2025.106594","DOIUrl":"10.1016/j.jinf.2025.106594","url":null,"abstract":"","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 3","pages":"Article 106594"},"PeriodicalIF":11.9,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144903882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The chikungunya virus outbreak in Foshan, China: A rising public health threat in tropical and subtropical regions","authors":"Jiayi Wang, Leiliang Zhang","doi":"10.1016/j.jinf.2025.106591","DOIUrl":"10.1016/j.jinf.2025.106591","url":null,"abstract":"","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 3","pages":"Article 106591"},"PeriodicalIF":11.9,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Blair Merrick , Désirée Prossomariti , Elizabeth Allen , Karen Bisnauthsing , Michael Kertanegara , Chrysi Sergaki , Adrien D. Le Guennec , Marc Delord , Jordana T. Bell , Maria R. Conte , David L. Moyes , Manu Shankar-Hari , Abdel Douiri , Anna L. Goodman , Debbie L. Shawcross , Simon D. Goldenberg
{"title":"Erratum to “Faecal microbiota transplant to ERadicate gastrointestinal carriage of Antibiotic-Resistant Organisms (FERARO): A feasibility randomised controlled trial” [J Infect 91 (2025) 106504]","authors":"Blair Merrick , Désirée Prossomariti , Elizabeth Allen , Karen Bisnauthsing , Michael Kertanegara , Chrysi Sergaki , Adrien D. Le Guennec , Marc Delord , Jordana T. Bell , Maria R. Conte , David L. Moyes , Manu Shankar-Hari , Abdel Douiri , Anna L. Goodman , Debbie L. Shawcross , Simon D. Goldenberg","doi":"10.1016/j.jinf.2025.106583","DOIUrl":"10.1016/j.jinf.2025.106583","url":null,"abstract":"","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 3","pages":"Article 106583"},"PeriodicalIF":11.9,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144842163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}