Rongling Zhang, Xiao Shang, Chunlei Wang, Hong Zhou, Nana Liu, Xiaochen Shen, Zeyi Wang, Jiuyang Xu, Dingrong Zhong, Hui Li, Bin Cao
Background The role of human rhinovirus (HRV) in adult lower respiratory tract infections (LRTIs) remains controversial due to limited direct evidence of alveolar tropism and age-specific clinical characterization. Objectives To determine HRV’s clinical impact, validate its capacity to infect lower respiratory tract cells, and identify predictors for HRV-associated pneumonia in adults. Methods In this retrospective study (January 2020–December 2023), all hospitalized adults screened for HRV via RT-PCR were enrolled for analysis. In BALF HRV RNA-positive patients with available transbronchial lung biopsy (TBLB) or transbronchial cryobiopsy (TBCB) specimens, immunofluorescence (IF) staining was used to assess infection of LRT cells. Multivariable logistic regression analyzed demographics, comorbidities, and symptoms. Results HRV was detected in 4.6% (437/9,544) of patients, with bimodal seasonal peaks (February–April and September–November). Co-infection occurred in 49.0% (214/437), predominantly bacteria (34.1%) and viruses (25.7%). Among the 437 HRV-positive patients, 224 cases complicated with pneumonia, but only 34 (7.8%) met the diagnostic criteria for simple viral pneumonia. Multivariate analysis identified male (OR 2.69, 95% CI 1.04-6.99, P = 0.042), fever (OR 3.79, 95% CI 1.52–9.44, P = 0.004) and cough (OR 7.33, 95% CI 1.64–32.83, P = 0.009) as independent predictors of simple rhinovirus pneumonia. IF staining confirmed HRV VP3 protein in TBLB/TBCB specimens in 61.5% (8/13) of cases, resolving debates about HRV’s LRT cells tropism. Conclusions This study provides the first histological evidence of HRV’s LRT cells infection in immunocompetent adults. Despite high co-infection rates, HRV independently drives pneumonia, particularly in males and those with fever or cough.
人类鼻病毒（HRV）在成人下呼吸道感染（LRTIs）中的作用仍然存在争议，因为关于肺泡性和年龄特异性临床特征的直接证据有限。目的确定HRV的临床影响，验证其感染下呼吸道细胞的能力，并确定成人HRV相关肺炎的预测因素。方法在这项回顾性研究中（2020年1月- 2023年12月），所有通过RT-PCR筛查的住院成人纳入分析。在可获得经支气管肺活检（TBLB）或经支气管低温活检（TBCB）标本的BALF HRV rna阳性患者中，使用免疫荧光（IF）染色来评估LRT细胞的感染。多变量logistic回归分析了人口统计学、合并症和症状。结果HRV检出率为4.6%(437/ 9544)，呈双峰型季节性高峰（2 - 4月和9 - 11月）。合并感染发生率为49.0%(214/437)，以细菌（34.1%）和病毒（25.7%）为主。437例hrv阳性患者中合并肺炎224例，但符合单纯性病毒性肺炎诊断标准的仅有34例（7.8%）。多因素分析发现，男性（OR 2.69, 95% CI 1.04-6.99, P = 0.042）、发烧（OR 3.79, 95% CI 1.52-9.44, P = 0.004）和咳嗽（OR 7.33, 95% CI 1.64-32.83, P = 0.009）是单纯鼻病毒肺炎的独立预测因子。IF染色在61.5%（8/13）的TBLB/TBCB标本中证实HRV VP3蛋白，解决了关于HRV LRT细胞趋向性的争论。结论本研究首次提供了免疫功能正常成人HRV LRT细胞感染的组织学证据。尽管合并感染率很高，但HRV独立驱动肺炎，特别是在男性和发烧或咳嗽患者中。
{"title":"Rhinovirus-associated lower respiratory tract infection in hospitalized adult patients: a retrospective cohort study","authors":"Rongling Zhang, Xiao Shang, Chunlei Wang, Hong Zhou, Nana Liu, Xiaochen Shen, Zeyi Wang, Jiuyang Xu, Dingrong Zhong, Hui Li, Bin Cao","doi":"10.1093/infdis/jiaf651","DOIUrl":"https://doi.org/10.1093/infdis/jiaf651","url":null,"abstract":"Background The role of human rhinovirus (HRV) in adult lower respiratory tract infections (LRTIs) remains controversial due to limited direct evidence of alveolar tropism and age-specific clinical characterization. Objectives To determine HRV’s clinical impact, validate its capacity to infect lower respiratory tract cells, and identify predictors for HRV-associated pneumonia in adults. Methods In this retrospective study (January 2020–December 2023), all hospitalized adults screened for HRV via RT-PCR were enrolled for analysis. In BALF HRV RNA-positive patients with available transbronchial lung biopsy (TBLB) or transbronchial cryobiopsy (TBCB) specimens, immunofluorescence (IF) staining was used to assess infection of LRT cells. Multivariable logistic regression analyzed demographics, comorbidities, and symptoms. Results HRV was detected in 4.6% (437/9,544) of patients, with bimodal seasonal peaks (February–April and September–November). Co-infection occurred in 49.0% (214/437), predominantly bacteria (34.1%) and viruses (25.7%). Among the 437 HRV-positive patients, 224 cases complicated with pneumonia, but only 34 (7.8%) met the diagnostic criteria for simple viral pneumonia. Multivariate analysis identified male (OR 2.69, 95% CI 1.04-6.99, P = 0.042), fever (OR 3.79, 95% CI 1.52–9.44, P = 0.004) and cough (OR 7.33, 95% CI 1.64–32.83, P = 0.009) as independent predictors of simple rhinovirus pneumonia. IF staining confirmed HRV VP3 protein in TBLB/TBCB specimens in 61.5% (8/13) of cases, resolving debates about HRV’s LRT cells tropism. Conclusions This study provides the first histological evidence of HRV’s LRT cells infection in immunocompetent adults. Despite high co-infection rates, HRV independently drives pneumonia, particularly in males and those with fever or cough.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145847262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Seher H Anjum, Jessica Hargarten, Brittany Dulek, Francisco Otaizo-Carrasquero, Winnie Trang, Shelley Kalsi, Morgan Similuk, Rajarshi Ghosh, Magdelena Walkiewicz-Yvon, Mari Tokita, Dima A Hammoud, Andrea Beri, Peter R Williamson
Background Cryptococcal meningitis (CM) is a leading cause of fungal meningitis globally. Cerebral venous sinus thrombosis (CVST), though a recognized complication, has been rarely reported in both HIV-positive and HIV-negative individuals. This study investigates the incidence, clinical course, genetic factors, and neuroimaging features of CVST in a retrospective cohort of previously healthy, non-HIV CM patients. Methods We reviewed medical records of 89 immunocompetent CM patients admitted to the NIH Clinical Center between January 2005 and April 2024. CVST incidence, clinical course, neuroimaging, and laboratory data were analyzed. Genetic analysis was performed to detect any thrombophilia-associated variants. To explore thrombosis-related gene expression during neuroinflammation, cerebrospinal fluid (CSF) cells collected at the time of cryptococcal post-infectious inflammatory response syndrome (cPIIRS) diagnosis were subjected to single-cell RNA sequencing. Results CVST occurred in 5.6% (CI 1.9% - 12.6%) of CM patients, a rate comparable to bacterial CNS infections. No known pathogenic or likely pathogenic variants in known thrombophilia-associated genes were identified. However, 44 genes previously linked to thrombosis showed elevated expression—defined as ≥150 single-cell sequencing reads—in a cPIIRS patient. Conclusion CVST is a clinically significant and potentially treatable complication of CM, even in individuals without prior clotting abnormalities. MRI and MRV of the brain are valuable diagnostic tools. The absence of identifiable thrombophilia mutations suggests that neurologic infection itself contributes to thrombotic risk. Notably, CSF gene expression patterns may serve as biomarkers for CVST susceptibility. Future case-control studies may validate these findings and uncover genetic risk factors contributing to this severe complication.
{"title":"Cerebral Venous Thrombosis in Previously Healthy Patients with Cryptococcal Meningitis","authors":"Seher H Anjum, Jessica Hargarten, Brittany Dulek, Francisco Otaizo-Carrasquero, Winnie Trang, Shelley Kalsi, Morgan Similuk, Rajarshi Ghosh, Magdelena Walkiewicz-Yvon, Mari Tokita, Dima A Hammoud, Andrea Beri, Peter R Williamson","doi":"10.1093/infdis/jiaf653","DOIUrl":"https://doi.org/10.1093/infdis/jiaf653","url":null,"abstract":"Background Cryptococcal meningitis (CM) is a leading cause of fungal meningitis globally. Cerebral venous sinus thrombosis (CVST), though a recognized complication, has been rarely reported in both HIV-positive and HIV-negative individuals. This study investigates the incidence, clinical course, genetic factors, and neuroimaging features of CVST in a retrospective cohort of previously healthy, non-HIV CM patients. Methods We reviewed medical records of 89 immunocompetent CM patients admitted to the NIH Clinical Center between January 2005 and April 2024. CVST incidence, clinical course, neuroimaging, and laboratory data were analyzed. Genetic analysis was performed to detect any thrombophilia-associated variants. To explore thrombosis-related gene expression during neuroinflammation, cerebrospinal fluid (CSF) cells collected at the time of cryptococcal post-infectious inflammatory response syndrome (cPIIRS) diagnosis were subjected to single-cell RNA sequencing. Results CVST occurred in 5.6% (CI 1.9% - 12.6%) of CM patients, a rate comparable to bacterial CNS infections. No known pathogenic or likely pathogenic variants in known thrombophilia-associated genes were identified. However, 44 genes previously linked to thrombosis showed elevated expression—defined as ≥150 single-cell sequencing reads—in a cPIIRS patient. Conclusion CVST is a clinically significant and potentially treatable complication of CM, even in individuals without prior clotting abnormalities. MRI and MRV of the brain are valuable diagnostic tools. The absence of identifiable thrombophilia mutations suggests that neurologic infection itself contributes to thrombotic risk. Notably, CSF gene expression patterns may serve as biomarkers for CVST susceptibility. Future case-control studies may validate these findings and uncover genetic risk factors contributing to this severe complication.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"118 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145822759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Francesco Branda,Giancarlo Ceccarelli,Marta Giovanetti,Fabio Scarpa,Massimo Ciccozzi
{"title":"Polio-Free, Not Risk-Free: Wastewater as Early Warning.","authors":"Francesco Branda,Giancarlo Ceccarelli,Marta Giovanetti,Fabio Scarpa,Massimo Ciccozzi","doi":"10.1093/infdis/jiaf643","DOIUrl":"https://doi.org/10.1093/infdis/jiaf643","url":null,"abstract":"","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145807929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mia Aguirre,Doris Ayala,Juan Ignacio Garcia,Yoscelina E Martinez-Lopez,Amberlee D Hicks,Nadine Chacon,Ashley Gay-Cobb,Alyssa Schami,Selena Zavala-Perez,Ilse A Dominguez-Trejo,America M Cruz-Gonzalez,Raul Loera-Salazar,Javier E Rodríguez-Herrera,Esperanza M Garcia-Oropesa,Miryoung Lee,Adrian Rendón,Shu-Hua Wang,Marcel Yotebieng,Carlton A Evans,Jordi B Torrelles,Blanca I Restrepo
BACKGROUNDWith >10 million new tuberculosis (TB) cases/year, a limitation to TB control is the lack of simple and accurate tests for TB diagnosis and drug-susceptibility testing (DST) in endemic regions. We evaluated the accuracy of the first-generation, low-complexity phenotypic TB test (1G test), designed for simultaneous Mtb detection and resistance to isoniazid, rifampicin and moxifloxacin, suitable for resource-limited settings.METHODSA cross-sectional study was conducted using sputa from 426 possible pulmonary TB subjects from two small Mexican cities bordering Texas. The 1G test was compared against phenotypic TB detection tests in the region [acid fast bacilli smear microscopy and Mycobacteria Growth Indicator Tube (MGIT) culture], and to MGIT-DST for resistance to isoniazid, rifampicin and moxifloxacin.FINDINGSThe 1G test demonstrated ≥98% sensitivity for Mtb detection, 100% sensitivity and 91% (rifampicin), 94% (isoniazid) and 97% (moxifloxacin) specificity for DST, and less contamination than the MGIT (3.5% vs. 8.1%; p<0.05). The 1G test time to detection (TTD) of Mtb and simultaneous DST was 17-days, while the MGIT-DST required two steps: 7 days for Mtb detection plus 14 more (total 21 days) for DST. Our study site DR-TB prevalence was 14% when testing all consecutively-enrolled participants vs. 6% by passive reporting.INTERPRETATIONThe 1G test is a low-complexity phenotypic TB diagnostic method that is a practical replacement to current culture-based tests. Future studies are warranted to evaluate the implementation of the 1G test in decentralized clinics that lack molecular tools, resources and expertise.
背景：结核病流行地区每年新发结核病病例高达1000万，结核病控制面临的一个限制是缺乏简单而准确的结核病诊断和药敏试验（DST）检测。我们评估了第一代低复杂性表型结核试验（1G试验）的准确性，该试验设计用于同时检测结核分枝杆菌和对异烟肼、利福平和莫西沙星的耐药性，适用于资源有限的环境。方法横断面研究使用来自德克萨斯州边境两个墨西哥小城市的426名疑似肺结核患者的痰液。将1G试验与该地区[抗酸杆菌涂片镜检和分枝杆菌生长指示管（MGIT）培养]表型结核检测试验进行比较，并与MGIT- dst试验比较异烟肼、利福平和莫西沙星的耐药性。结果：1G试验对Mtb的检测灵敏度≥98%，对DST的检测灵敏度为100%，利福平为91%，异烟肼为94%，莫西沙星为97%，污染小于MGIT （3.5% vs. 8.1%; p<0.05）。Mtb和同步DST的1G检测到检测时间（TTD）为17天，而mgt -DST需要两个步骤：Mtb检测7天加上DST 14天（共21天）。在我们的研究现场，当对所有连续入组的参与者进行检测时，耐药结核病患病率为14%，而被动报告为6%。解释：1G测试是一种低复杂性的表型结核诊断方法，是目前基于培养的测试的实用替代品。未来的研究需要评估1G测试在缺乏分子工具、资源和专业知识的分散诊所中的实施情况。
{"title":"Accuracy of the phenotypic 1G test to detect Mycobacterium tuberculosis and drug resistance from sputa in the US-Mexico border.","authors":"Mia Aguirre,Doris Ayala,Juan Ignacio Garcia,Yoscelina E Martinez-Lopez,Amberlee D Hicks,Nadine Chacon,Ashley Gay-Cobb,Alyssa Schami,Selena Zavala-Perez,Ilse A Dominguez-Trejo,America M Cruz-Gonzalez,Raul Loera-Salazar,Javier E Rodríguez-Herrera,Esperanza M Garcia-Oropesa,Miryoung Lee,Adrian Rendón,Shu-Hua Wang,Marcel Yotebieng,Carlton A Evans,Jordi B Torrelles,Blanca I Restrepo","doi":"10.1093/infdis/jiaf638","DOIUrl":"https://doi.org/10.1093/infdis/jiaf638","url":null,"abstract":"BACKGROUNDWith >10 million new tuberculosis (TB) cases/year, a limitation to TB control is the lack of simple and accurate tests for TB diagnosis and drug-susceptibility testing (DST) in endemic regions. We evaluated the accuracy of the first-generation, low-complexity phenotypic TB test (1G test), designed for simultaneous Mtb detection and resistance to isoniazid, rifampicin and moxifloxacin, suitable for resource-limited settings.METHODSA cross-sectional study was conducted using sputa from 426 possible pulmonary TB subjects from two small Mexican cities bordering Texas. The 1G test was compared against phenotypic TB detection tests in the region [acid fast bacilli smear microscopy and Mycobacteria Growth Indicator Tube (MGIT) culture], and to MGIT-DST for resistance to isoniazid, rifampicin and moxifloxacin.FINDINGSThe 1G test demonstrated ≥98% sensitivity for Mtb detection, 100% sensitivity and 91% (rifampicin), 94% (isoniazid) and 97% (moxifloxacin) specificity for DST, and less contamination than the MGIT (3.5% vs. 8.1%; p<0.05). The 1G test time to detection (TTD) of Mtb and simultaneous DST was 17-days, while the MGIT-DST required two steps: 7 days for Mtb detection plus 14 more (total 21 days) for DST. Our study site DR-TB prevalence was 14% when testing all consecutively-enrolled participants vs. 6% by passive reporting.INTERPRETATIONThe 1G test is a low-complexity phenotypic TB diagnostic method that is a practical replacement to current culture-based tests. Future studies are warranted to evaluate the implementation of the 1G test in decentralized clinics that lack molecular tools, resources and expertise.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"118 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145807928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Benedikt Strunz, Qiuyao Zhan, Tanvi Khera, Julia Hengst, Marija Jankovic, Katja Deterding, Annika Niehrs, Markus Cornberg, Cheng-Jian Xu, Heiner Wedemeyer, Niklas K Björkström
Acute infection with hepatitis C virus (HCV) is a rare event that can be treated successfully with direct-acting antivirals (DAAs). As Natural killer (NK) cells play an important role during the natural course of acute HCV, we assessed the NK cell compartment via flow cytometry and single-cell sequencing in longitudinally sampled patients with acute HCV and compared this to healthy controls and patients with chronic HCV. At the transcriptomic level, we identified a subset of highly activated NK cells with a robust type-I interferon imprint. While the population of activated NK cells vanished after DAA-mediated cure, a long-term phenotypic imprint of infection was observed in comparison to healthy controls. Collectively, these data suggest an interferon-driven rise of an activated NK cell population during acute hepatitis C, that is largely restored upon viral clearance. This study provides insights into the immunological basis for successful antiviral response to hepatitis C.
{"title":"Transient interferon-driven NK cell activation in acute hepatitis C","authors":"Benedikt Strunz, Qiuyao Zhan, Tanvi Khera, Julia Hengst, Marija Jankovic, Katja Deterding, Annika Niehrs, Markus Cornberg, Cheng-Jian Xu, Heiner Wedemeyer, Niklas K Björkström","doi":"10.1093/infdis/jiaf654","DOIUrl":"https://doi.org/10.1093/infdis/jiaf654","url":null,"abstract":"Acute infection with hepatitis C virus (HCV) is a rare event that can be treated successfully with direct-acting antivirals (DAAs). As Natural killer (NK) cells play an important role during the natural course of acute HCV, we assessed the NK cell compartment via flow cytometry and single-cell sequencing in longitudinally sampled patients with acute HCV and compared this to healthy controls and patients with chronic HCV. At the transcriptomic level, we identified a subset of highly activated NK cells with a robust type-I interferon imprint. While the population of activated NK cells vanished after DAA-mediated cure, a long-term phenotypic imprint of infection was observed in comparison to healthy controls. Collectively, these data suggest an interferon-driven rise of an activated NK cell population during acute hepatitis C, that is largely restored upon viral clearance. This study provides insights into the immunological basis for successful antiviral response to hepatitis C.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145836136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eyal Elias, Danielle Keidar-Friedman, Nadav Sorek, Orit Raz, Sharon Ovnat Tamir, Liam Aspit, Dan Bar Yaacov
Background Adenosine-to-inosine (A-to-I) mRNA editing can alter protein sequence and function, enabling bacteria to express two RNA and protein versions encoded by the same gene. However, its prevalence and significance in clinical bacterial settings remain unclear. Methods We collected ten Escherichia coli and seven Pseudomonas aeruginosa isolates from hospitalized patients with urinary tract infections (UTI) or ear infections. Whole-genome and transcriptome sequencing were performed for each isolate, followed by Sanger sequencing for selected sites. Results We present the first comprehensive analysis of A-to-I RNA editing in pathogenic bacteria isolated from hospitalized patients. We identified dozens of A-to-I RNA editing sites, including novel sites not previously reported in non-pathogenic E. coli and P. aeruginosa strains. We found that E. coli exhibits higher editing levels and a greater number of editing sites than P. aeruginosa. Most editing sites are embedded within a conserved 7-base motif and are frequently located in predicted stem-loop RNA secondary structures, highlighting the importance of both sequence and structure for editing site recognition in both the examined species. Most editing events occur in mRNA and often result in non-synonymous amino acid changes, with a notable prevalence of tyrosine-to-cysteine substitutions. Finally, we observed that editing patterns are similar between antibiotic-resistant and sensitive isolates, suggesting a more general role in the biology of the examined species. Conclusions A-to-I RNA editing is a feature of pathogenic bacteria isolated from clinical samples. Our findings expand current knowledge of bacterial RNA editing in clinical contexts and provide a framework for future functional investigations.
腺苷-肌苷（A-to-I） mRNA编辑可以改变蛋白质序列和功能，使细菌能够表达由同一基因编码的两种RNA和蛋白质版本。然而，其患病率和意义在临床细菌设置仍不清楚。方法从尿路感染或耳部感染住院患者中分离10株大肠杆菌和7株铜绿假单胞菌。对每个分离物进行全基因组和转录组测序，然后对选定的位点进行Sanger测序。我们首次对从住院患者中分离的致病菌中的A-to-I RNA编辑进行了全面分析。我们鉴定了数十个A-to-I RNA编辑位点，包括以前未在非致病性大肠杆菌和铜绿假单胞菌菌株中报道的新位点。我们发现大肠杆菌比铜绿假单胞菌表现出更高的编辑水平和更多的编辑位点。大多数编辑位点都嵌入在保守的7碱基基序中，并且经常位于预测的茎环RNA二级结构中，这突出了序列和结构对两种被研究物种中编辑位点识别的重要性。大多数编辑事件发生在mRNA中，通常导致非同义氨基酸的变化，酪氨酸到半胱氨酸的替换显著流行。最后，我们观察到耐药菌株和敏感菌株之间的编辑模式相似，这表明在所检测物种的生物学中具有更普遍的作用。结论a -to- i RNA编辑是临床分离致病菌的一个特征。我们的发现扩大了目前在临床环境中对细菌RNA编辑的了解，并为未来的功能研究提供了一个框架。
{"title":"The landscape and regulatory determinants of A-to-I RNA editing in Escherichia coli and Pseudomonas aeruginosa isolated from patients with urinary tract and ear infections","authors":"Eyal Elias, Danielle Keidar-Friedman, Nadav Sorek, Orit Raz, Sharon Ovnat Tamir, Liam Aspit, Dan Bar Yaacov","doi":"10.1093/infdis/jiaf645","DOIUrl":"https://doi.org/10.1093/infdis/jiaf645","url":null,"abstract":"Background Adenosine-to-inosine (A-to-I) mRNA editing can alter protein sequence and function, enabling bacteria to express two RNA and protein versions encoded by the same gene. However, its prevalence and significance in clinical bacterial settings remain unclear. Methods We collected ten Escherichia coli and seven Pseudomonas aeruginosa isolates from hospitalized patients with urinary tract infections (UTI) or ear infections. Whole-genome and transcriptome sequencing were performed for each isolate, followed by Sanger sequencing for selected sites. Results We present the first comprehensive analysis of A-to-I RNA editing in pathogenic bacteria isolated from hospitalized patients. We identified dozens of A-to-I RNA editing sites, including novel sites not previously reported in non-pathogenic E. coli and P. aeruginosa strains. We found that E. coli exhibits higher editing levels and a greater number of editing sites than P. aeruginosa. Most editing sites are embedded within a conserved 7-base motif and are frequently located in predicted stem-loop RNA secondary structures, highlighting the importance of both sequence and structure for editing site recognition in both the examined species. Most editing events occur in mRNA and often result in non-synonymous amino acid changes, with a notable prevalence of tyrosine-to-cysteine substitutions. Finally, we observed that editing patterns are similar between antibiotic-resistant and sensitive isolates, suggesting a more general role in the biology of the examined species. Conclusions A-to-I RNA editing is a feature of pathogenic bacteria isolated from clinical samples. Our findings expand current knowledge of bacterial RNA editing in clinical contexts and provide a framework for future functional investigations.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145812935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
William J McCarthy,Frederick Ferguson,Lillian Gelberg
{"title":"For Optimal HIV Viral Load Reduction, Increase Intake of Gut Microbe-Friendly Foods: Comment on Palar et al.","authors":"William J McCarthy,Frederick Ferguson,Lillian Gelberg","doi":"10.1093/infdis/jiaf383","DOIUrl":"https://doi.org/10.1093/infdis/jiaf383","url":null,"abstract":"","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"20 1","pages":"e1060-e1061"},"PeriodicalIF":0.0,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The United States leads the world in biomedical innovation, with NIH-funded research driving transformative advances in cancer, HIV, and gene therapy. Yet, these breakthroughs cannot achieve their full impact in a fragmented and inequitable health system. Millions remain uninsured, preventive care is undervalued, and social determinants perpetuate life expectancy gaps. Political efforts to restrict or defund the NIH threaten progress and disproportionately harm underserved populations. Biomedical research alone cannot fix systemic failures but strengthening science while repairing care delivery systems is essential to improving population health and ensuring that innovations benefit all.
{"title":"Why Americans are Dying Younger? NIH Is Not the Problem. Our Broken Healthcare Delivery Is.","authors":"Rachel Bender Ignacio,Jade Pagkas-Bather,Gregg Gonsalves,Sara Gianella","doi":"10.1093/infdis/jiaf592","DOIUrl":"https://doi.org/10.1093/infdis/jiaf592","url":null,"abstract":"The United States leads the world in biomedical innovation, with NIH-funded research driving transformative advances in cancer, HIV, and gene therapy. Yet, these breakthroughs cannot achieve their full impact in a fragmented and inequitable health system. Millions remain uninsured, preventive care is undervalued, and social determinants perpetuate life expectancy gaps. Political efforts to restrict or defund the NIH threaten progress and disproportionately harm underserved populations. Biomedical research alone cannot fix systemic failures but strengthening science while repairing care delivery systems is essential to improving population health and ensuring that innovations benefit all.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145785846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background Sporotrichosis is a chronic, deep fungal infection of skin caused by S.schenckii. Macrophages are predominant in S.schenckii infected skin and able to phagocytize and kill the fungus. Local hyperthermia is effective to treat sporotrichosis, however, its mechanism of action remains not fully understood. Methods Using single-cell RNA sequencing of sporotrichosis lesions, coupled with in vitro and in vivo sporotrichosis models, we investigated the role of TRAF1 and NOS2. Mechanistic studies included co-immunoprecipitation, ubiquitination assays, and site-directed mutagenesis. Therapeutic mechanism of hyperthermia were evaluated in vivo and in vitro. Results We demonstrated for the first time that TRAF1 could delay the healing of sporotrichosis by inhibiting phagocytosis and killing of macrophages to S.schenckii. This effect of TRAF1 is caused by binding NOS2 to regulate its expression and enzymatic activity, through inhibition of NOS2 ubiquitination and subsequent proteasome-induced degradation. Our team's previous research has demonstrated the efficacy of hyperthermia in treating sporotrichosis. Our experiments indicate that hyperthermia can downregulate the expression of TRAF1 and NOS2 in macrophages. Conclusions We identify TRAF1-mediated stabilization of NOS2 as a key immune evasion mechanism in S. schenckii infection. Local hyperthermia represents a targeted therapy against this pathway, offering a novel strategy for enhancing the therapeutic effect of hyperthermia.
{"title":"TRAF1 Inhibits Macrophage Killing of Sporothrix schenckii by Enhancing NOS2 Expression and Activity","authors":"Congcong He, Ruiqun Qi, Yuxiao Hong, Xinghua Gao","doi":"10.1093/infdis/jiaf646","DOIUrl":"https://doi.org/10.1093/infdis/jiaf646","url":null,"abstract":"Background Sporotrichosis is a chronic, deep fungal infection of skin caused by S.schenckii. Macrophages are predominant in S.schenckii infected skin and able to phagocytize and kill the fungus. Local hyperthermia is effective to treat sporotrichosis, however, its mechanism of action remains not fully understood. Methods Using single-cell RNA sequencing of sporotrichosis lesions, coupled with in vitro and in vivo sporotrichosis models, we investigated the role of TRAF1 and NOS2. Mechanistic studies included co-immunoprecipitation, ubiquitination assays, and site-directed mutagenesis. Therapeutic mechanism of hyperthermia were evaluated in vivo and in vitro. Results We demonstrated for the first time that TRAF1 could delay the healing of sporotrichosis by inhibiting phagocytosis and killing of macrophages to S.schenckii. This effect of TRAF1 is caused by binding NOS2 to regulate its expression and enzymatic activity, through inhibition of NOS2 ubiquitination and subsequent proteasome-induced degradation. Our team's previous research has demonstrated the efficacy of hyperthermia in treating sporotrichosis. Our experiments indicate that hyperthermia can downregulate the expression of TRAF1 and NOS2 in macrophages. Conclusions We identify TRAF1-mediated stabilization of NOS2 as a key immune evasion mechanism in S. schenckii infection. Local hyperthermia represents a targeted therapy against this pathway, offering a novel strategy for enhancing the therapeutic effect of hyperthermia.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145807682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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