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Discriminating ST3 and non-ST3 Staphylococcus lugdunensis using MALDI-TOF and machine learning analysis. 利用MALDI-TOF和机器学习分析鉴别ST3和非ST3型卢顿葡萄球菌。
IF 3.7 2区 医学 Q2 IMMUNOLOGY Pub Date : 2026-03-17 DOI: 10.1016/j.jmii.2026.03.005
Yu-Hsiang Ou, Lee-Chung Lin, Hsin-Yao Wang, Jang-Jih Lu
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引用次数: 0
Diffuse alveolar hemorrhage in systemic lupus erythematosus during the COVID-19 era-a retrospective analysis with mechanistic investigation. COVID-19时期系统性红斑狼疮弥漫性肺泡出血的回顾性分析及机制研究
IF 3.7 2区 医学 Q2 IMMUNOLOGY Pub Date : 2026-03-12 DOI: 10.1016/j.jmii.2026.03.004
Chia-Tse Weng, Yu-Tung Hsieh, Wei-Chieh Lin, Yi-Ting Yen, Pin Ling, Hung-Wen Tsai, Chrong-Reen Wang

Background: Viral infection plays an important role in driving activity of autoimmune diseases. Preceding SARS-CoV-2 infection has been observed to trigger disease flares in systemic lupus erythematosus (SLE). Besides cytomegalovirus, SARS-CoV-2 can induce pulmonary capillaritis to develop diffuse alveolar hemorrhage (DAH), a respiratory emergency of SLE.

Objective: Owing to lack of comprehensive studies for SARS-CoV-2-triggered DAH in SLE, we conducted a monocentric analysis with mechanistic investigation.

Methods: Hospitalized SLE patients were retrospectively analyzed for the DAH manifestation in the COVID-19 era since December 2019, focusing on those with preceding SARS-CoV-2 infection. Peripheral blood (PB) and lung tissues samples and immune/alveolus cell lines were used for mechanistic research.

Results: Twenty-five DAH episodes were identified in 21 SLE patients (3% occurrence), all in disease flares with high activity scores. During the domestic omicron variant outbreak, 7 patients (33%) had preceding SARS-CoV-2 infection, 3 to 7 weeks earlier to the onset of DAH, while they had elevated IL-6, nitro-oxidative stress- and cell death-associated molecules levels in PB and lung tissues with enhanced apoptosis formation. IL-6-stimulated alveolus/immune cells exhibited a dose-dependent increase in nitro-oxidative stress- and cell death-associated molecules levels, up-regulated p38MAPK/NF-κB-p65 phosphorylation, raised ROS expression and enhanced apoptosis formation. These findings implicated cell death induced by IL-6-activated nitro-oxidative stress to generate circulating immune complexes with pulmonary deposition as the mechanism for DAH preceded by SARS-CoV-2 infection in SLE.

Conclusion: The DAH manifestation preceded by SARS-CoV-2 infection is observed in SLE with disease flares, requiring careful monitor and management of COVID-19 in such patients.

背景:病毒感染在自身免疫性疾病的发病过程中起着重要作用。先前的SARS-CoV-2感染已被观察到可引发系统性红斑狼疮(SLE)的疾病发作。除巨细胞病毒外,SARS-CoV-2还可诱导肺毛细血管炎发展为弥漫性肺泡出血(DAH),这是SLE的呼吸急症。目的:由于缺乏对SLE中sars - cov -2引发的DAH的全面研究,我们进行了单中心分析和机制调查。方法:回顾性分析2019年12月以来住院SLE患者在COVID-19时代的DAH表现,重点分析既往感染SARS-CoV-2的患者。采用外周血和肺组织标本及免疫/肺泡细胞系进行机制研究。结果:在21例SLE患者中发现25次DAH发作(发生率为3%),均发生在活动评分较高的疾病发作中。在国内的组粒变异暴发期间,7名患者(33%)在DAH发病前3至7周曾感染过SARS-CoV-2,同时他们的PB和肺组织中IL-6、硝基氧化应激和细胞死亡相关分子水平升高,细胞凋亡形成增强。il -6刺激的肺泡/免疫细胞表现出剂量依赖性的氮氧化应激和细胞死亡相关分子水平升高,p38MAPK/NF-κ b -p65磷酸化上调,ROS表达升高,细胞凋亡形成增强。这些发现表明,il -6激活的硝基氧化应激诱导细胞死亡,产生循环免疫复合物并伴有肺沉积,这是SLE患者在感染SARS-CoV-2之前发生DAH的机制。结论:伴有疾病发作的SLE患者存在先出现DAH后出现SARS-CoV-2感染的情况,需要对这类患者进行严密的COVID-19监测和管理。
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引用次数: 0
Global perspectives on pertussis epidemiology, macrolide resistance, and management in the post-COVID-19 era (2020-2024). 后covid -19时代(2020-2024)百日咳流行病学、大环内酯类药物耐药性和管理的全球视角
IF 3.7 2区 医学 Q2 IMMUNOLOGY Pub Date : 2026-03-06 DOI: 10.1016/j.jmii.2026.03.002
Quying Yang, Yijun Yang, Bingjie Liu, Lina Xu, Yu Ma, Jing Zhou, Yuqing Wang, Chuangli Hao, Wujun Jiang

Pertussis, caused by Bordetella pertussis, remains a substantial public health threat despite long-standing vaccination programs. Widespread non-pharmaceutical interventions (NPIs) during COVID-19 were accompanied by marked declines in reported pertussis activity in many settings. However, relaxation of containment measures has been followed by resurgence, characterized by atypical outbreak patterns and shifts in case distribution, bacterial genotypes, and affected populations. Emerging evidence suggests that these changes are multifactorial, including altered contact patterns and immunity gap, disruptions and recovery in routine immunization and surveillance, waning or suboptimal vaccine-induced protection, pathogen adaptation, and improved case detection through expanded diagnostic capabilities. Addressing these challenges will require coordinated strategies to restore and optimize immunization delivery, strengthen surveillance and laboratory capacity (including resistance monitoring), and update clinical management guidance in the context of macrolide-resistant B. pertussis. Continued research is needed to define setting-specific drivers and to inform next-generation vaccines and integrated control strategies in the post-pandemic era.

百日咳,由百日咳博德泰拉引起,仍然是一个重大的公共卫生威胁,尽管长期的疫苗接种计划。在COVID-19期间,在许多情况下,广泛的非药物干预措施伴随着报告的百日咳活动的显着下降。然而,在放松控制措施之后,又出现了死灰复燃,其特点是非典型暴发模式以及病例分布、细菌基因型和受影响人群的变化。新出现的证据表明,这些变化是多因素的,包括接触模式和免疫缺口的改变、常规免疫和监测的中断和恢复、疫苗引起的保护减弱或次优、病原体适应以及通过扩大诊断能力改进的病例发现。应对这些挑战将需要协调战略,以恢复和优化免疫接种,加强监测和实验室能力(包括耐药性监测),并在耐大环内酯百日咳背景下更新临床管理指南。需要继续进行研究,以确定特定环境的驱动因素,并为大流行后时代的下一代疫苗和综合控制战略提供信息。
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引用次数: 0
Etiological identification of Orientia tsutsugamushi by metagenomic next-generation sequencing in an adult with septic shock in Taiwan. 台湾1例成人感染性休克之恙虫病东方体病原学鉴定。
IF 3.7 2区 医学 Q2 IMMUNOLOGY Pub Date : 2026-02-19 DOI: 10.1016/j.jmii.2026.02.002
Tian-Yu You, Nan-Yao Lee, Wen-Chia Tsai, Ching-Lung Lo, Po-Ta Chen, Szu-Ying Chen, Hao-En Jan, Wen-Chien Ko
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引用次数: 0
Characterization of the oral microbiota of Kawasaki disease patients by metagenomic analysis: A pilot study. 通过宏基因组分析川崎病患者口腔微生物群的特征:一项初步研究。
IF 3.7 2区 医学 Q2 IMMUNOLOGY Pub Date : 2026-02-06 DOI: 10.1016/j.jmii.2026.01.007
Yuantao Tong, Yuxin Chen, Yifan Dong, Kaining Chen, Juhua Yang, Xuefan Dong, Xin Wan, Ziheng Luo, Junjie Fang, Yunfeng Liu, Wei Li, Zhouping Wang, Xiaoqiong Gu

Background: Kawasaki disease (KD) is an acute febrile systemic vasculitis characterized by vascular inflammation. Its pathogenesis has been linked to the infiltration of IgA+ plasma cells within the respiratory tract, suggesting the upper airway may act as a potential portal of entry. However, evidence connecting respiratory infections to KD remains limited. This study aimed to explore the relationship between oral microbiota and KD development.

Methods: Oral swab samples were collected from 25 KD patients before and after intravenous immunoglobulin (IVIG) treatment, as well as from 25 healthy controls. Metagenomic sequencing was performed to characterize overall microbial composition and identify potential microbial markers associated with KD.

Results: Significant alterations in oral microbiota composition were observed between KD patients and healthy controls. The diversity of oral microbiota in KD patients was markedly lower than that in healthy controls, and exhibited an upward trend following IVIG treatment. Elevated levels of Streptococcus, Prevotella, and Veillonella, along with reduced levels of Haemophilus, Neisseria, and Rothia, were closely associated with KD development. Putative novel pathogen Abiotrophia defectiva was significantly enriched in patients with KD. Correlation analysis revealed that the relative abundances of several Haemophilus species were positively correlated with albumin levels in KD patients before IVIG treatment. Additionally, the anti-inflammatory bacterium Rothia mucilaginosa may play a protective role against the development of coronary artery lesions in KD.

Conclusion: These findings provide new evidence that distinct alterations in the oral microbiome are associated with KD development. Oral microbiota-based biomarkers may represent a potential strategy for KD therapy.

背景:川崎病(Kawasaki disease, KD)是一种以血管炎症为特征的急性发热性全身血管炎。其发病机制与呼吸道内IgA+浆细胞的浸润有关,提示上呼吸道可能是一个潜在的入口。然而,将呼吸道感染与KD联系起来的证据仍然有限。本研究旨在探讨口腔微生物群与KD发展的关系。方法:收集25例KD患者静脉注射免疫球蛋白(IVIG)治疗前后的口腔拭子样本,以及25例健康对照。进行宏基因组测序以表征总体微生物组成并鉴定与KD相关的潜在微生物标记物。结果:在KD患者和健康对照组之间观察到口腔微生物群组成的显著变化。KD患者口腔微生物群多样性明显低于健康对照组,IVIG治疗后呈上升趋势。链球菌、普雷沃氏菌和细孔菌水平的升高,以及嗜血杆菌、奈瑟菌和罗氏菌水平的降低与KD的发展密切相关。推测的新型病原体无营养缺陷在KD患者中显著富集。相关分析显示,在IVIG治疗前,KD患者中几种嗜血杆菌的相对丰度与白蛋白水平呈正相关。此外,抗炎细菌粘液罗氏菌可能对KD患者冠状动脉病变的发展起保护作用。结论:这些发现为口腔微生物组的明显改变与KD的发展相关提供了新的证据。基于口腔微生物群的生物标志物可能代表KD治疗的潜在策略。
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引用次数: 0
The implementation of the Infection Control Map-an integrated, visual online information system-enhanced infection control practices and reduced the incidence of multidrug-resistant organisms in a medical intensive care unit. 感染控制地图(一种综合的可视化在线信息系统)的实施加强了感染控制实践,并减少了重症监护病房中耐多药微生物的发生率。
IF 3.7 2区 医学 Q2 IMMUNOLOGY Pub Date : 2026-02-06 DOI: 10.1016/j.jmii.2026.02.001
Chih-Hao Chen, Wei-Cheng Chen, Wen-Sheng Feng, How-Yang Tseng, Yi-Cheng Shen, Hsu-Yuan Chen, Chih-Yen Tu, Jiun-Yi Lin, Ching-Yao Chou, Chun-Wei Tu, Yow-Wen Hsieh, Hsiu-Hsien Lin, Mao-Wang Ho, Kao-Pin Hwang, Wu-Huei Hsu, Po-Ren Hsueh, Der-Yang Cho

Background: Fragmented and siloed nature of healthcare data leads to insufficient recognition of infection control priorities and poor adherence to preventive measures. We evaluated the impact of a visualized and integrated online information system on the infection control practice and incidence of multidrug-resistant organisms (MDROs), antimicrobial consumptions, and clinical outcomes in a medical intensive care unit (ICU).

Methods: Patients hospitalized in one medical ICU during July 1, 2023, to November 30, 2024, were collected, and were analyzed by clinical outcomes, the incidence rate of healthcare-associated MDROs, and the antimicrobial consumptions before and after the implementation of Infection Control Map (ICM). Another ICU was selected as comparison.

Results: A total of 775 patients were included and divided into two periods: Pre-intervention period (n = 262), and Intervention period (n = 513). There were no statistical differences among demographics except the Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) score, which was higher in the Intervention period than that of Pre-intervention period (30.0 vs 25.0, p = 0.000). The incidence rate of MDROs decreased over time (tau = -0.53, p = 0.019), especially the methicillin-resistant Staphylococcus aureus (1.5 vs 0.3 per 1000 patient-days, incidence rate ratio = 0.2, p = 0.012), as well as the consumption of meropenem (tau = -0.53, p = 0.003). There was significant decrease in 30-day all-cause mortality after the ICM use by multivariate analysis.

Conclusion: The implementation of the ICM significantly strengthened infection control practices, resulting in a marked reduction in healthcare-associated MRSA incidence, targeted antimicrobial usage, and 30-day all-cause mortality.

背景:卫生保健数据的碎片化和孤立性导致对感染控制重点的认识不足和对预防措施的依从性差。我们评估了一个可视化和集成的在线信息系统对感染控制实践和多药耐药菌(MDROs)发生率、抗菌药物使用和重症监护病房(ICU)临床结果的影响。方法:收集2023年7月1日至2024年11月30日在某内科ICU住院的患者,对实施感染控制图(ICM)前后的临床结局、卫生保健相关mdro发生率及抗菌药物使用情况进行分析。选择另一ICU作为对照。结果:共纳入775例患者,分为干预前(262例)和干预期(513例)。除急性生理评估和慢性健康评估II (APACHE II)评分在干预期高于干预前(30.0比25.0,p = 0.000)外,其他人口统计学差异无统计学意义。MDROs的发生率随着时间的推移而下降(tau = -0.53, p = 0.019),尤其是耐甲氧西林金黄色葡萄球菌(1.5 vs 0.3 / 1000患者-天,发病率比= 0.2,p = 0.012),以及美罗培南的摄入量(tau = -0.53, p = 0.003)。多因素分析显示,使用ICM后30天全因死亡率显著降低。结论:ICM的实施显著加强了感染控制实践,导致与医疗保健相关的MRSA发病率、靶向抗菌药物使用和30天全因死亡率显著降低。
{"title":"The implementation of the Infection Control Map-an integrated, visual online information system-enhanced infection control practices and reduced the incidence of multidrug-resistant organisms in a medical intensive care unit.","authors":"Chih-Hao Chen, Wei-Cheng Chen, Wen-Sheng Feng, How-Yang Tseng, Yi-Cheng Shen, Hsu-Yuan Chen, Chih-Yen Tu, Jiun-Yi Lin, Ching-Yao Chou, Chun-Wei Tu, Yow-Wen Hsieh, Hsiu-Hsien Lin, Mao-Wang Ho, Kao-Pin Hwang, Wu-Huei Hsu, Po-Ren Hsueh, Der-Yang Cho","doi":"10.1016/j.jmii.2026.02.001","DOIUrl":"https://doi.org/10.1016/j.jmii.2026.02.001","url":null,"abstract":"<p><strong>Background: </strong>Fragmented and siloed nature of healthcare data leads to insufficient recognition of infection control priorities and poor adherence to preventive measures. We evaluated the impact of a visualized and integrated online information system on the infection control practice and incidence of multidrug-resistant organisms (MDROs), antimicrobial consumptions, and clinical outcomes in a medical intensive care unit (ICU).</p><p><strong>Methods: </strong>Patients hospitalized in one medical ICU during July 1, 2023, to November 30, 2024, were collected, and were analyzed by clinical outcomes, the incidence rate of healthcare-associated MDROs, and the antimicrobial consumptions before and after the implementation of Infection Control Map (ICM). Another ICU was selected as comparison.</p><p><strong>Results: </strong>A total of 775 patients were included and divided into two periods: Pre-intervention period (n = 262), and Intervention period (n = 513). There were no statistical differences among demographics except the Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) score, which was higher in the Intervention period than that of Pre-intervention period (30.0 vs 25.0, p = 0.000). The incidence rate of MDROs decreased over time (tau = -0.53, p = 0.019), especially the methicillin-resistant Staphylococcus aureus (1.5 vs 0.3 per 1000 patient-days, incidence rate ratio = 0.2, p = 0.012), as well as the consumption of meropenem (tau = -0.53, p = 0.003). There was significant decrease in 30-day all-cause mortality after the ICM use by multivariate analysis.</p><p><strong>Conclusion: </strong>The implementation of the ICM significantly strengthened infection control practices, resulting in a marked reduction in healthcare-associated MRSA incidence, targeted antimicrobial usage, and 30-day all-cause mortality.</p>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146183611","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}
引用次数: 0
Non-SARS-CoV-2 respiratory tract infections in pediatric populations during the pandemic. 大流行期间儿科人群中的非sars - cov -2呼吸道感染。
IF 3.7 2区 医学 Q2 IMMUNOLOGY Pub Date : 2026-02-02 DOI: 10.1016/j.jmii.2026.01.006
Yi-Ting Chen, Ya-Chih Cheng, Kuo-Chen Weng, Meng-Shuan Lin, Hui-Yu Liao, Shu-Yuan Ho, Jhong-Lin Wu, Chien-Chang Lee, Sui-Yuan Chang

Background: Respiratory tract infections (RTIs) remain a major concern in pediatric care, as they can pose life-threatening risks to children. While SARS-CoV-2 receives substantial public concern, identifying other respiratory pathogens in SARS-CoV-2-negative patients is crucial for guiding clinical management.

Methods: In this study, the etiology of RTIs among 156 SARS-CoV-2-negative children in 2022 was analyzed using BIOFIRE® FilmArray® Respiratory Panel 2.1 assay, VIASURE rhinovirus + enterovirus detection kit, and an in-house realtime-PCR for human bocavirus.

Results: Of the 156 samples tested with the FilmArray®, 96 (61.5%) were positive for viral pathogens, with human rhinovirus/enterovirus (HRV/EV) being the most prevalent (92.7%). Targeted PCR assay confirmed that 97.8% of HRV/EV detections were rhinoviruses, which were significantly associated with asthma (OR = 9.0, 95% CI = 2.0-14.2, P = 0.005). Human bocavirus (HBoV) was detected in 40 out of 144 samples (27.8%) using real-time PCR. Multivariable analysis identified age as the only factor associated with HBoV detection (OR = 0.8, 95% CI: 0.7-1.0, P = 0.014), although it was noted 45.5% of pneumonia cases were HBoV-positive. Overall, 75.7% of co-detections involved HBoV, most frequently with HRV/EV. Co-detections were significantly associated with male gender (OR = 2.9, 95% CI = 1.2-7.3, P = 0.024) and fever (OR = 6.3, 95% CI = 2.0-19.8, P = 0.002).

Conclusion: Our study demonstrates the occurrence of viral co-detections in pediatric patients with non-SARS-CoV-2 RTIs during the pandemic. The frequent detection of rhinovirus and HBoV warrants further investigation into their clinical significance in Taiwanese children with RTIs.

背景:呼吸道感染(RTIs)仍然是儿科护理的一个主要问题,因为它们可能对儿童构成威胁生命的风险。虽然SARS-CoV-2引起了公众的广泛关注,但在SARS-CoV-2阴性患者中识别其他呼吸道病原体对于指导临床管理至关重要。方法:采用BIOFIRE®FilmArray®Respiratory Panel 2.1检测试剂盒、VIASURE鼻病毒+肠道病毒检测试剂盒和室内实时荧光定量pcr对2022年156例sars - cov -2阴性儿童RTIs的病因进行分析。结果:在156份检测样本中,96份(61.5%)病毒病原体阳性,其中以人鼻病毒/肠病毒(HRV/EV)最常见(92.7%)。目的PCR检测证实97.8%的HRV/EV为鼻病毒,鼻病毒与哮喘有显著相关性(OR = 9.0, 95% CI = 2.0 ~ 14.2, P = 0.005)。144份样品中有40份(27.8%)检测到人博病毒(HBoV)。多变量分析发现年龄是与HBoV检测相关的唯一因素(OR = 0.8, 95% CI: 0.7-1.0, P = 0.014),尽管注意到45.5%的肺炎病例HBoV阳性。总体而言,75.7%的合并检测涉及HBoV,最常见的是HRV/EV。共检出与男性(OR = 2.9, 95% CI = 1.2 ~ 7.3, P = 0.024)和发热(OR = 6.3, 95% CI = 2.0 ~ 19.8, P = 0.002)显著相关。结论:我们的研究表明,在大流行期间,非sars - cov -2呼吸道感染的儿科患者中出现了病毒共检测。鼻病毒和HBoV的频繁检出值得进一步研究其在台湾儿童呼吸道感染中的临床意义。
{"title":"Non-SARS-CoV-2 respiratory tract infections in pediatric populations during the pandemic.","authors":"Yi-Ting Chen, Ya-Chih Cheng, Kuo-Chen Weng, Meng-Shuan Lin, Hui-Yu Liao, Shu-Yuan Ho, Jhong-Lin Wu, Chien-Chang Lee, Sui-Yuan Chang","doi":"10.1016/j.jmii.2026.01.006","DOIUrl":"https://doi.org/10.1016/j.jmii.2026.01.006","url":null,"abstract":"<p><strong>Background: </strong>Respiratory tract infections (RTIs) remain a major concern in pediatric care, as they can pose life-threatening risks to children. While SARS-CoV-2 receives substantial public concern, identifying other respiratory pathogens in SARS-CoV-2-negative patients is crucial for guiding clinical management.</p><p><strong>Methods: </strong>In this study, the etiology of RTIs among 156 SARS-CoV-2-negative children in 2022 was analyzed using BIOFIRE® FilmArray® Respiratory Panel 2.1 assay, VIASURE rhinovirus + enterovirus detection kit, and an in-house realtime-PCR for human bocavirus.</p><p><strong>Results: </strong>Of the 156 samples tested with the FilmArray®, 96 (61.5%) were positive for viral pathogens, with human rhinovirus/enterovirus (HRV/EV) being the most prevalent (92.7%). Targeted PCR assay confirmed that 97.8% of HRV/EV detections were rhinoviruses, which were significantly associated with asthma (OR = 9.0, 95% CI = 2.0-14.2, P = 0.005). Human bocavirus (HBoV) was detected in 40 out of 144 samples (27.8%) using real-time PCR. Multivariable analysis identified age as the only factor associated with HBoV detection (OR = 0.8, 95% CI: 0.7-1.0, P = 0.014), although it was noted 45.5% of pneumonia cases were HBoV-positive. Overall, 75.7% of co-detections involved HBoV, most frequently with HRV/EV. Co-detections were significantly associated with male gender (OR = 2.9, 95% CI = 1.2-7.3, P = 0.024) and fever (OR = 6.3, 95% CI = 2.0-19.8, P = 0.002).</p><p><strong>Conclusion: </strong>Our study demonstrates the occurrence of viral co-detections in pediatric patients with non-SARS-CoV-2 RTIs during the pandemic. The frequent detection of rhinovirus and HBoV warrants further investigation into their clinical significance in Taiwanese children with RTIs.</p>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146203984","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}
引用次数: 0
Hha toxin regulates diverse phenotypes of uropathogenic Proteus mirabilis including virulence Hha毒素调节尿路致病性奇异变形杆菌的多种表型,包括毒力。
IF 3.7 2区 医学 Q2 IMMUNOLOGY Pub Date : 2026-02-01 Epub Date: 2025-08-29 DOI: 10.1016/j.jmii.2025.08.016
Yueh-Jung Chao , Yuan-Ju Lee , Hsuan- Hsuan Chen , Cheng-Yen Kao , Shwu-Jen Liaw

Background

To disclose Proteus mirabilis copper detoxification mechanisms, we performed Tn5-mutagenesis and an hha gene-disrupted mutant was isolated, exhibiting increased copper sensitivity. We investigated the role of Hha in P. mirabilis, focusing on the virulence aspects.

Methods

Assays of copper susceptibility, swarming/swimming, biofilm formation, persister cell formation, killing by macrophages, adhesion, invasion, urothelial cell cytokine expression, wax moth virulence, were performed. The invertible element assay, TEM, EMSA and SDM were used to examine MR/P fimbria expression, flagellar production, Hha-flhDC promoter binding and the importance of Hha 13th amino acid cysteine (Hha C13), respectively. RT-PCR was conducted to demonstrate the tomB-hha operon. Hha-related gene expression and regulation were elucidated by RT-qPCR and transcriptional reporter assay.

Results

We showed P. mirabilis hha and tomB form an operon and TomB antagonized Hha toxicity. The Hha was involved in copper susceptibility, swimming/swarming, biofilm formation and persister cell formation. The hha mutant had lower adhesion/invasion abilities, triggered higher cytokine expression of urothelial cells and was more sensitive to macrophage killing and attenuated in wax moth. P. mirabilis Hha C13 is crucial in toxicity and Hha-TomB interaction. Deletion of hha reduced relA/rpoS expression. CpxR controlled hha promoter activity. Finally, copper was the signal to induce cpxR/hha expression.

Conclusion

We disclosed that P. mirabilis Hha of the toxin-antitoxin system (TA) participates in virulence and its regulation by copper-sensing CpxR. This work provides Hha as a potential drug target for combating P. mirabilis urinary tract infections and opens new perspectives for studying TA aiming at controlling bacterial virulence.
背景:为了揭示奇异变形杆菌的铜解毒机制,我们进行了tn5诱变,并分离出一个hha基因破坏的突变体,表现出对铜的敏感性增加。我们研究了Hha在P. mirabilis中的作用,重点是毒力方面。方法:采用铜敏感性、蜂群/游泳、生物膜形成、持久性细胞形成、巨噬细胞杀伤、粘附、侵袭、尿路上皮细胞细胞因子表达、蜡蛾毒力测定。采用可逆元件法、透射电镜(TEM)、EMSA和SDM分别检测MR/P菌毛表达、鞭毛产生、ha- flhdc启动子结合和Hha 13氨基酸半胱氨酸(Hha C13)的重要性。采用RT-PCR方法鉴定了tomB-hha操纵子。利用RT-qPCR和转录报告基因法分析ha相关基因的表达和调控。结果:我们发现神奇假单胞菌hha和古墓形成一个操纵子,古墓可拮抗hha毒性。Hha参与了铜的敏感性、游动/群集、生物膜的形成和持久性细胞的形成。hha突变体具有较低的粘附/侵袭能力,引起尿路上皮细胞细胞因子表达升高,对巨噬细胞杀伤和蜡蛾减毒更敏感。P. mirabilis Hha C13在毒性和Hha- tomb相互作用中起关键作用。hha的缺失降低了relA/rpoS的表达。CpxR控制hha启动子活性。最后,铜是诱导cpxR/hha表达的信号。结论:我们发现P. mirabilis毒素-抗毒素系统(TA)中的Hha参与了铜敏感CpxR的毒力及其调控。本研究为Hha作为抗神奇假单胞菌尿路感染的潜在药物靶点提供了依据,并为研究TA控制细菌毒力开辟了新的视角。
{"title":"Hha toxin regulates diverse phenotypes of uropathogenic Proteus mirabilis including virulence","authors":"Yueh-Jung Chao ,&nbsp;Yuan-Ju Lee ,&nbsp;Hsuan- Hsuan Chen ,&nbsp;Cheng-Yen Kao ,&nbsp;Shwu-Jen Liaw","doi":"10.1016/j.jmii.2025.08.016","DOIUrl":"10.1016/j.jmii.2025.08.016","url":null,"abstract":"<div><h3>Background</h3><div>To disclose <em>Proteus mirabilis</em> copper detoxification mechanisms, we performed Tn5-mutagenesis and an <em>hha</em> gene<em>-</em>disrupted mutant was isolated, exhibiting increased copper sensitivity. We investigated the role of Hha in <em>P. mirabilis</em>, focusing on the virulence aspects.</div></div><div><h3>Methods</h3><div>Assays of copper susceptibility, swarming/swimming, biofilm formation, persister cell formation, killing by macrophages, adhesion, invasion, urothelial cell cytokine expression, wax moth virulence, were performed. The invertible element assay, TEM, EMSA and SDM were used to examine MR/P fimbria expression, flagellar production, Hha-<em>flhDC</em> promoter binding and the importance of Hha 13th amino acid cysteine (Hha C13), respectively. RT-PCR was conducted to demonstrate the <em>tomB-hha</em> operon. Hha-related gene expression and regulation were elucidated by RT-qPCR and transcriptional reporter assay.</div></div><div><h3>Results</h3><div>We showed <em>P. mirabilis hha and tomB</em> form an operon and TomB antagonized Hha toxicity. The Hha was involved in copper susceptibility, swimming/swarming, biofilm formation and persister cell formation. The <em>hha</em> mutant had lower adhesion/invasion abilities, triggered higher cytokine expression of urothelial cells and was more sensitive to macrophage killing and attenuated in wax moth. <em>P. mirabilis</em> Hha C13 is crucial in toxicity and Hha-TomB interaction. Deletion of <em>hha</em> reduced <em>relA</em>/<em>rpoS</em> expression. CpxR controlled <em>hha</em> promoter activity. Finally, copper was the signal to induce <em>cpxR</em>/<em>hha</em> expression.</div></div><div><h3>Conclusion</h3><div>We disclosed that <em>P. mirabilis</em> Hha of the toxin-antitoxin system (TA) participates in virulence and its regulation by copper-sensing CpxR. This work provides Hha as a potential drug target for combating <em>P. mirabilis</em> urinary tract infections and opens new perspectives for studying TA aiming at controlling bacterial virulence.</div></div>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":"59 1","pages":"Pages 124-135"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980102","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}
引用次数: 0
Efficacy and safety of ten-day bismuth quadruple therapy for first-line anti-Helicobacter pylori infection in the elderly- A multicenter real-world report 10天铋四联疗法治疗老年人一线抗幽门螺杆菌感染的疗效和安全性-一项多中心真实世界报告。
IF 3.7 2区 医学 Q2 IMMUNOLOGY Pub Date : 2026-02-01 Epub Date: 2025-07-02 DOI: 10.1016/j.jmii.2025.06.010
Kuo-Hsuan Huang , Wei-Chen Tai , Feng-Woey Tsay , Pin-I Hsu , Deng-Chyang Wu , Song-Seng Loke , Chih-Chien Yao , Seng-Kee Chuah , Chih-Ming Liang

Background

Aging may influence the effectiveness of Helicobacter pylori (H. pylori) eradication. The purpose of this study was to evaluate the efficacy and safety of 10-day bismuth quadruple therapy as a first-line treatment for H. pylori infection in elderly individuals.

Methods

We conducted a retrospective analysis of prospectively collected data from September 2018 to December 2021 in southern Taiwan. All patients received 10-day quadruple therapy consisting of rabeprazole 20 mg twice daily, bismuth subcitrate 120 mg four times daily, metronidazole 500 mg three times daily, and tetracycline 500 mg four times daily. Patients were categorized into two groups: an elderly group (aged ≥65) and a control group (aged <65).

Results

The study included 231 naive patients receiving 10-day quadruple therapy. The eradication rates in the elderly and control groups were 80.3 % (95 % confidence interval [CI]: 68.1 %–89.4 %) and 85.3 % (95 % CI: 79.1 %–90.3 %) (P = 0.364), respectively, in the intention-to-treat analysis. In the per-protocol analysis, eradication rates were 89.1 % (95 % CI: 77.8 %–95.9 %) for the elderly group and 94.8 % (95 % CI: 90.0 %–97.7 %) for the control group (P = 0.149). Adverse event rates were 34.5 % in the elderly group and 27.5 % in the control group (P = 0.322). Compliance was slightly lower in the elderly group than the control group (89.1 % vs. 95.4 %, P = 0.096).

Conclusions

The efficacy of 10-day bismuth quadruple therapy as a first-line treatment for H. pylori was comparable between elderly and non-elderly cohorts, with similar levels of adverse effects.
背景:衰老可能影响幽门螺杆菌(h.p ylori)的根除效果。本研究的目的是评估10天铋四联疗法作为老年人幽门螺杆菌感染一线治疗的有效性和安全性。方法:我们对2018年9月至2021年12月在台湾南部前瞻性收集的数据进行回顾性分析。所有患者均接受为期10天的四联治疗,包括雷贝拉唑20 mg每日2次,亚柠檬酸铋120 mg每日4次,甲硝唑500 mg每日3次,四环素500 mg每日4次。患者分为两组:老年组(≥65岁)和对照组(老年)。结果:该研究纳入了231例接受10天四联治疗的初治患者。意向治疗分析中,老年人和对照组的根除率分别为80.3%(95%可信区间[CI]: 68.1% ~ 89.4%)和85.3% (95% CI: 79.1% ~ 90.3%) (P = 0.364)。按方案分析,老年组根除率为89.1% (95% CI: 77.8% ~ 95.9%),对照组根除率为94.8% (95% CI: 90.0% ~ 97.7%) (P = 0.149)。老年组不良事件发生率为34.5%,对照组为27.5% (P = 0.322)。老年组依从性略低于对照组(89.1%比95.4%,P = 0.096)。结论:10天铋四联疗法作为一线治疗幽门螺杆菌的疗效在老年和非老年队列中相当,不良反应水平相似。
{"title":"Efficacy and safety of ten-day bismuth quadruple therapy for first-line anti-Helicobacter pylori infection in the elderly- A multicenter real-world report","authors":"Kuo-Hsuan Huang ,&nbsp;Wei-Chen Tai ,&nbsp;Feng-Woey Tsay ,&nbsp;Pin-I Hsu ,&nbsp;Deng-Chyang Wu ,&nbsp;Song-Seng Loke ,&nbsp;Chih-Chien Yao ,&nbsp;Seng-Kee Chuah ,&nbsp;Chih-Ming Liang","doi":"10.1016/j.jmii.2025.06.010","DOIUrl":"10.1016/j.jmii.2025.06.010","url":null,"abstract":"<div><h3>Background</h3><div>Aging may influence the effectiveness of <em>Helicobacter pylori</em> (<em>H. pylori</em>) eradication. The purpose of this study was to evaluate the efficacy and safety of 10-day bismuth quadruple therapy as a first-line treatment for <em>H. pylori</em> infection in elderly individuals.</div></div><div><h3>Methods</h3><div>We conducted a retrospective analysis of prospectively collected data from September 2018 to December 2021 in southern Taiwan. All patients received 10-day quadruple therapy consisting of rabeprazole 20 mg twice daily, bismuth subcitrate 120 mg four times daily, metronidazole 500 mg three times daily, and tetracycline 500 mg four times daily. Patients were categorized into two groups: an elderly group (aged ≥65) and a control group (aged &lt;65).</div></div><div><h3>Results</h3><div>The study included 231 naive patients receiving 10-day quadruple therapy. The eradication rates in the elderly and control groups were 80.3 % (95 % confidence interval [CI]: 68.1 %–89.4 %) and 85.3 % (95 % CI: 79.1 %–90.3 %) (P = 0.364), respectively, in the intention-to-treat analysis. In the per-protocol analysis, eradication rates were 89.1 % (95 % CI: 77.8 %–95.9 %) for the elderly group and 94.8 % (95 % CI: 90.0 %–97.7 %) for the control group (P = 0.149). Adverse event rates were 34.5 % in the elderly group and 27.5 % in the control group (P = 0.322). Compliance was slightly lower in the elderly group than the control group (89.1 % vs. 95.4 %, P = 0.096).</div></div><div><h3>Conclusions</h3><div>The efficacy of 10-day bismuth quadruple therapy as a first-line treatment for <em>H. pylori</em> was comparable between elderly and non-elderly cohorts, with similar levels of adverse effects.</div></div>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":"59 1","pages":"Pages 91-97"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144577057","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}
引用次数: 0
NADPH Oxidase 4 Deficiency Enhances Dendritic Cell-mediated IL-12 Production and Th1 Responses in Mycobacterium tuberculosis Infection NADPH氧化酶4缺乏增强结核分枝杆菌感染树突状细胞介导的IL-12产生和Th1反应
IF 3.7 2区 医学 Q2 IMMUNOLOGY Pub Date : 2026-02-01 Epub Date: 2025-08-10 DOI: 10.1016/j.jmii.2025.08.004
Seunghyun Lee , Hongmin Kim , Yura Ha , Hong-Hee Choi , Lee-Han Kim , Sangwon Choi , Kyungmin Kim , Ji-Hwan Ryu , Sung Jae Shin , Ju Mi Lee

Background

Mycobacterium tuberculosis (Mtb) infection triggers oxidative stress, necessitating host mechanisms to maintain redox balance. The NADPH oxidase (NOX) family, which produces reactive oxygen species, plays an integral part in this process. While the protective role of NOX2 in Mtb infection is well-studied, the function of NOX4 remains unclear.

Methods

To investigate the impact of NOX4, we infected C57BL/6 wild-type (WT) and NOX4-deficient (Nox4−/−) mice with the Mtb K strain, assessing bacterial burdens, lung pathology, and immune responses. Then, we analyzed cytokine production and signaling pathways to explore the interaction between dendritic cells (DCs) and T cells.

Results

Nox4−/− mice exhibited reduced bacterial burden and milder lung pathology compared to WT mice, accompanied by increased DC infiltration and a higher frequency of CD4+ T cells of the Th1 subset that secrete interferon-gamma (IFN-γ) in the lungs. Interestingly, ex vivo experiments showed no significant difference in IFN-γ production by T cells from WT and Nox4−/− mice when activated using antibody-coated beads. However, Mtb-infected bone marrow-derived DCs (BMDCs) from Nox4−/− mice markedly enhanced IFN-γ production in WT T cells. Further investigation into the role of NOX4 in DCs revealed that BMDCs from Nox4−/− mice infected with Mtb produced significantly higher levels of IL-12. This elevation was attributed to enhanced activation of IRF1, mediated by the AKT/GSK-3β signaling pathway.

Conclusion

NOX4 negatively regulates IL-12 production in Mtb-infected DCs, suppressing Th1-mediated immunity. Its absence enhances Th1 responses, improves immune control of Mtb. Targeting NOX4 may improve tuberculosis outcomes by strengthening host immunity.
背景:结核分枝杆菌(Mtb)感染触发氧化应激,需要宿主机制来维持氧化还原平衡。产生活性氧的NADPH氧化酶(NOX)家族在这一过程中起着不可或缺的作用。虽然NOX2在Mtb感染中的保护作用已被充分研究,但NOX4的功能尚不清楚。方法:为了研究NOX4的影响,我们用Mtb K菌株感染C57BL/6野生型(WT)和NOX4缺陷(NOX4- /-)小鼠,评估细菌负荷、肺部病理和免疫反应。然后,我们分析了细胞因子的产生和信号通路,以探索树突状细胞(dc)和T细胞之间的相互作用。结果:与WT小鼠相比,Nox4-/-小鼠表现出更轻的细菌负担和更轻的肺部病理,同时伴有DC浸润增加和Th1亚群中分泌干扰素-γ (IFN-γ)的CD4+ T细胞频率更高。有趣的是,体外实验显示,当使用抗体包被珠活化时,WT和Nox4-/-小鼠的T细胞产生的IFN-γ没有显著差异。然而,来自Nox4-/-小鼠的mtb感染的骨髓来源dc (bmdc)显着增强了WT T细胞中IFN-γ的产生。对NOX4在dc中的作用的进一步研究表明,感染Mtb的NOX4 -/-小鼠bmdc产生的IL-12水平显著升高。这种升高归因于AKT/GSK-3β信号通路介导的IRF1激活增强。结论:NOX4负性调节mtb感染dc中IL-12的产生,抑制th1介导的免疫。它的缺失增强了Th1反应,改善了对结核分枝杆菌的免疫控制。靶向NOX4可能通过增强宿主免疫来改善结核病的预后。
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引用次数: 0
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Journal of Microbiology Immunology and Infection
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