Journal of Infectious Diseases最新文献_第2页

Utility of nasopharyngeal aspirate over other upper airway sampling approaches for cellular immunology during respiratory viral infection. 在呼吸道病毒感染期间，鼻咽吸入比其他上呼吸道取样方法更适用于细胞免疫。

IF 4.5 2区医学

Journal of Infectious Diseases Pub Date : 2026-05-05 DOI: 10.1093/infdis/jiag245

Sara Falck-Jones, Björn Österberg, Eric Åhlberg, Julia Svensson, Afandi Charles, Meng Yu, Avinash Padhi, Vijay Joshua, Jeanette Grundström, Ryan Falck-Jones, Max Bell, Lena Bergqvist, Anna Smed-Sörensen

引用次数: 0

Structure-guided design of calcium-dependent protein kinase 1 (CDPK1) inhibitors for cryptosporidiosis. 隐孢子虫病钙依赖性蛋白激酶1 （CDPK1）抑制剂的结构指导设计。

IF 4.5 2区医学

Journal of Infectious Diseases Pub Date : 2026-05-04 DOI: 10.1093/infdis/jiag242

Wissarut Wijitrmektong, Ryan Choi, Matthew A Hulverson, Lijun Liu, Anne Cooper, Kevin P Battaile, Elizabeth K Harmon, Denise Ann Dayao, Lauren Huerta, Saul Tzipori, Case W McNamara, Malina A Bakowski, Scott Lovell, Wesley C Van Voorhis, Gregory D Cuny

{"title":"Structure-guided design of calcium-dependent protein kinase 1 (CDPK1) inhibitors for cryptosporidiosis.","authors":"Wissarut Wijitrmektong, Ryan Choi, Matthew A Hulverson, Lijun Liu, Anne Cooper, Kevin P Battaile, Elizabeth K Harmon, Denise Ann Dayao, Lauren Huerta, Saul Tzipori, Case W McNamara, Malina A Bakowski, Scott Lovell, Wesley C Van Voorhis, Gregory D Cuny","doi":"10.1093/infdis/jiag242","DOIUrl":"https://doi.org/10.1093/infdis/jiag242","url":null,"abstract":"Background: Calcium-dependent protein kinase 1 (CDPK1) has emerged as a protozoan specific target for the treatment of cryptosporidiosis. A previous study identified pyridopyrimidinones as new Cryptosporidium parvum (Cp) CDPK1 inhibitors with potent growth inhibition against C. parvum and C. hominis. Docking analyses suggested the unique positioning of the kinase's αC-helix could present refinement opportunities.Methods: Compounds designed to optimize the pyridopyrimidinones focused on the back-pocket region predicted to be proximal to the αC-helix, the solvent exposed region and the ATP ribose-binding site. Designed derivatives were synthesized and assessed for CpCDPK1 and Src kinase inhibition and for Cryptosporidium spp., growth inhibition in mammalian cells. AMP/Mg+2 and three inhibitors were co-crystalized with CpCDPK1, and two inhibitors were profiled for kinase selectivity.Results: WIN 4-88 was identified with CpCDPK1 (IC50 = 0.056 μM), and growth inhibition of zoonotic C. parvum (NLuc EC50 = 0.042 μM), anthroponotic C. parvum (Tu114 EC50 = 0.030 μM), and C. hominis Tu502 (EC50 = 0.062 μM), as well as enhanced kinome selectivity. The crystal structures confirmed the predicted binding mode, indicating key interactions with hinge residue Y155, similar orientations of the solvent expose moieties, occupancy of the back-pocket near the αC-helix and for one inhibitor containing a solubilizing hydroxyethyl attached to the central heterocycle extension into the ATP ribose-binding site.Conclusions: The expanded structure-activity relationship and structural insights will potentially be applicable to other chemotypes with similar binding modes and will enhance development of CpCDPK1 inhibitors for the treatment of cryptosporidiosis.","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147845422","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

Correction to: Epidemiology and Risk Factors of Norovirus Infections Among Diarrhea Patients Admitted to Tertiary Care Hospitals in Bangladesh. 修正：孟加拉国三级医院收治的腹泻患者中诺如病毒感染的流行病学和危险因素。

IF 4.5 2区医学

Journal of Infectious Diseases Pub Date : 2026-05-04 DOI: 10.1093/infdis/jiag234

引用次数: 0

Comment on B-Cell Subset Representation Predicts SARS-CoV-2 Vaccine Response in Solid Organ Transplant Recipients. b细胞亚群表征预测实体器官移植受者SARS-CoV-2疫苗反应的研究进展

IF 4.5 2区医学

Journal of Infectious Diseases Pub Date : 2026-04-29 DOI: 10.1093/infdis/jiag055

Pınar Belviranlı Keskin

引用次数: 0

Protocols for Randomized Controlled Trials: Advancing Transparency in Infectious Diseases. 随机对照试验方案：提高传染病的透明度。

IF 4.5 2区医学

Journal of Infectious Diseases Pub Date : 2026-04-29 DOI: 10.1093/infdis/jiag134

Jean-Jacques Parienti, Roger Bedimo, Cynthia L Sears, Paul E Sax

引用次数: 0

Modeling the Impact of Case Finding for Tuberculosis: The Role of Infection Dynamics. 模拟肺结核病例发现的影响：感染动力学的作用。

IF 4.5 2区医学

Journal of Infectious Diseases Pub Date : 2026-04-29 DOI: 10.1093/infdis/jiag050

Theresa S Ryckman, Sourya Shrestha, Anthony T Fojo, Parastu Kasaie, David W Dowdy, Emily A Kendall

{"title":"Modeling the Impact of Case Finding for Tuberculosis: The Role of Infection Dynamics.","authors":"Theresa S Ryckman, Sourya Shrestha, Anthony T Fojo, Parastu Kasaie, David W Dowdy, Emily A Kendall","doi":"10.1093/infdis/jiag050","DOIUrl":"10.1093/infdis/jiag050","url":null,"abstract":"Background: Many individuals previously infected with Mycobacterium tuberculosis (Mtb) may clear their infections or experience substantially reduced progression risks over time. Such dynamics suggest that recent transmission is more important in driving TB incidence in high-burden settings than previously estimated; thus, the impact of interventions to reduce transmission (eg, community-based active case finding) may also be greater than previously thought.Methods: We constructed 2 models of Mtb transmission that differed only in the inclusion of a clearance mechanism. We calibrated these models independently to the same set of epidemiological data representative of a high-TB-burden setting (India) and used the calibrated models to project the impact of illustrative biennial active case-finding campaigns (75% coverage; 65% sensitivity).Results: The estimated annual risk of Mtb infection and prevalence of recent infection were substantially higher in the model with Mtb clearance, despite being fit to the same data. The clearance model projected a greater impact of case finding on the incidence of TB disease: 45% [95% uncertainty interval 28%-57%] reduction compared to no intervention after 10 years versus 11% [6%-18%] in the model without clearance.Conclusions: Models that allow for Mtb clearance are evidence-supported and project greater impact from active case finding than models that do not include these dynamics.","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"e990-e998"},"PeriodicalIF":4.5,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reply to Yates and Barr. 衡量结核病患者传染性的挑战及其对隔离指南的影响。

IF 4.5 2区医学

Journal of Infectious Diseases Pub Date : 2026-04-29 DOI: 10.1093/infdis/jiaf656

Ruvandhi R Nathavitharana, Veronica Ueckermann, Elsabe de Kock, Edward Nardell

引用次数: 0

TLR4-MyD88-NF-κB Signaling in the Airway Epithelium Promotes Acinetobacter baumannii Clearance. 气道上皮TLR4-MyD88-NF-κB信号通路促进鲍曼不动杆菌清除。

IF 4.5 2区医学

Journal of Infectious Diseases Pub Date : 2026-04-29 DOI: 10.1093/infdis/jiag061

Jisun Kim, Gyu Lee Kim, Alexander Lemenze, Dane Parker

{"title":"TLR4-MyD88-NF-κB Signaling in the Airway Epithelium Promotes Acinetobacter baumannii Clearance.","authors":"Jisun Kim, Gyu Lee Kim, Alexander Lemenze, Dane Parker","doi":"10.1093/infdis/jiag061","DOIUrl":"10.1093/infdis/jiag061","url":null,"abstract":"Background: Acinetobacter baumannii is a high-priority Gram-negative respiratory pathogen associated with high morbidity and mortality. While many components of the innate immune response to A. baumannii have been studied, the specific role of the airway epithelium in coordinating the innate immune response to A. baumannii is largely undefined. In this study we demonstrate that NF-κB signaling within airway epithelial cells is essential for effective pulmonary clearance of A. baumannii.Methods: To understand the role of epithelial signaling, we utilized several mouse models of infection.Results: Using both pharmacological and conditional knockouts of the NF-κB subunit RelA (p65) in airway epithelial cells of mice, we observed substantial defects in bacterial clearance from the airways and lungs. This impaired clearance was associated with significant reductions in early neutrophil recruitment to the airway, which was linked to decreased expression of key neutrophil chemokines (G-CSF, GM-CSF, and CCL20) at both the transcript and protein levels. RNA sequencing of sorted airway epithelial cells revealed that NF-κB activity was required for transcription of inflammatory and chemotactic genes. Administration of exogenous neutrophil chemokines was able to restore early neutrophil recruitment in epithelial RelA-deficient mice, but only partially rescued bacterial clearance, suggesting additional mechanisms beyond granulocyte chemokine induction. We also show that airway epithelial expression of TLR4 and its adaptor protein MyD88 are also required for effective bacterial clearance from the airway, identifying a TLR4-MyD88-NF-κB axis.Conclusions: These findings highlight the airway epithelium as a critical site of innate immune sensing and coordinating the pulmonary host defense against A. baumannii.","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"696-705"},"PeriodicalIF":4.5,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146120922","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

When PD-1 Meets Plaque: Making CD8 Senescence Signals Clinically Actionable in Treated HIV. 当PD-1遇到斑块：使CD8衰老信号在治疗的HIV中具有临床可操作性。

IF 4.5 2区医学

Journal of Infectious Diseases Pub Date : 2026-04-29 DOI: 10.1093/infdis/jiag081

Xiaowei Zhang

引用次数: 0

Response to Dr Belviranli Keskin's Comments. 对Belviranli Keskin博士评论的回应。

IF 4.5 2区医学

Journal of Infectious Diseases Pub Date : 2026-04-29 DOI: 10.1093/infdis/jiag056

James J Knox, Ingi Lee, Emily A Blumberg, Eline T Luning Prak

引用次数: 0