The Journal of Infectious Diseases最新文献

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Estimating ZIKV seroprevalence in a DENV endemic population: the use of blood donors and multiplex serology to monitor arbovirus outbreaks in the Dutch Caribbean. 估计登革热流行人群中寨卡病毒血清流行率:利用献血者和多重血清学监测荷属加勒比地区虫媒病毒暴发
The Journal of Infectious Diseases Pub Date : 2025-05-27 DOI: 10.1093/infdis/jiaf281
Louella M R Kasbergen,Reina S Sikkema,Felicity Chandler,Janko H G van Beek,Yaskara Halabi,Norédiz Lourents,Eugene G Maduro,Izzy Gerstenbluth,Ashley Duits,Marion P G Koopmans
{"title":"Estimating ZIKV seroprevalence in a DENV endemic population: the use of blood donors and multiplex serology to monitor arbovirus outbreaks in the Dutch Caribbean.","authors":"Louella M R Kasbergen,Reina S Sikkema,Felicity Chandler,Janko H G van Beek,Yaskara Halabi,Norédiz Lourents,Eugene G Maduro,Izzy Gerstenbluth,Ashley Duits,Marion P G Koopmans","doi":"10.1093/infdis/jiaf281","DOIUrl":"https://doi.org/10.1093/infdis/jiaf281","url":null,"abstract":"BACKGROUNDThe geographic range of flaviviruses is expanding, as evidenced by the increase in dengue virus (DENV) cases and the recent emergence of Zika virus (ZIKV) in the Americas. Studying seroprevalence of flaviviruses in (hyper)endemic regions is challenging due to extensive antibody cross-reactivity. Over the past decade, Aruba and Curaçao have experienced DENV and ZIKV outbreaks, of which the magnitude and impact remain unclear due to the challenges of disentangling DENV from ZIKV (past) infection.METHODSHere, we study the potential utility of blood donors for monitoring the extent of circulation, on two Caribbean islands. We report a longitudinal cross-sectional study using randomly selected blood donor sera (n=715) during the ZIKV outbreaks on Aruba and Curaçao (January 2016-July 2017). Flavivirus seroprevalence was estimated using a validated multiplex protein microarray containing NS1 proteins for 11 flaviviruses, in combination with confirmation virus neutralization tests (VNT) on a selection of sera.RESULTSIt was possible to disentangle ZIKV exposure from exposure to other flaviviruses. In Curaçao, the seroprevalence of ZIKV antibodies was 25% and significantly higher than the prevalence of antibodies attributable to ZIKV exposure in Aruba (8%). Flavivirus IgG antibody titers increased with age (p-value <0.05).CONCLUSIONSThis methodology allows estimation of ZIKV seroprevalence during and after the ZIKV outbreaks. This study shows the importance of including age in the interpretation of serology data. Furthermore, it gives insights into the complex antibody (background) patterns of flaviviruses over time, and highlights the utility of an existing voluntary blood donor program to monitor and respond to (flavivirus) outbreaks.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"171 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144146182","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}
引用次数: 0
Prevotella intermedia Synergistically Exacerbates Pneumonia Induced by Oral Streptococci 中普雷沃氏菌协同加重口服链球菌引起的肺炎
The Journal of Infectious Diseases Pub Date : 2025-05-27 DOI: 10.1093/infdis/jiaf278
Hiroki Ashizawa, Naoki Iwanaga, Kazuki Nemoto, Tatsuro Hirayama, Masataka Yoshida, Kazuaki Takeda, Shotaro Ide, Masato Tashiro, Naoki Hosogaya, Takahiro Takazono, Kosuke Kosai, Noriho Sakamoto, Koichi Izumikawa, Mariko Naito, Yoshimasa Tanaka, Katsunori Yanagihara, Kazuhiro Yatera, Hiroshi Mukae
{"title":"Prevotella intermedia Synergistically Exacerbates Pneumonia Induced by Oral Streptococci","authors":"Hiroki Ashizawa, Naoki Iwanaga, Kazuki Nemoto, Tatsuro Hirayama, Masataka Yoshida, Kazuaki Takeda, Shotaro Ide, Masato Tashiro, Naoki Hosogaya, Takahiro Takazono, Kosuke Kosai, Noriho Sakamoto, Koichi Izumikawa, Mariko Naito, Yoshimasa Tanaka, Katsunori Yanagihara, Kazuhiro Yatera, Hiroshi Mukae","doi":"10.1093/infdis/jiaf278","DOIUrl":"https://doi.org/10.1093/infdis/jiaf278","url":null,"abstract":"Background The precise mechanisms of respiratory infection caused by oral anaerobic bacteria remain elusive. Unexpectedly, bacterial microbiota analysis using 16S rRNA revealed “hidden” mixed infections of anaerobic bacteria and commensal oral Streptococcus species in patients with community-acquired pneumonia (CAP). The study aimed to elucidate the mechanisms by which Prevotella intermedia exacerbates oral streptococcal pneumonia. Methods Oral streptococci were oropharyngeally administered with the culture supernatants of P. intermedia (PiSup) in mice to assess survival, microbial burden, inflammatory responses, and host response using unbiased bulk RNA sequencing. Additionally, genetically engineered strains of P. intermedia were used to identify pathogenic factors. Results Seven-week-old female C57BL/6J mice treated with the combination of Streptococcus spp. and PiSup exhibited significantly worse survival and increased microbial burden in the lungs and spleen compared to Streptococcus spp. and control medium. RNA sequencing of whole lung revealed disruption of neutrophilic bactericidal activity due to NADP downregulation, accompanied by reduced myeloperoxidase production in mixed infections, leading to dysfunctional neutrophil accumulation in the lungs. Notably, PiSup from strains bearing mutations in the type IX secretion pathway (ΔporT or ΔporK) failed to worsen the mixed infection. Conclusions Prevotella intermedia exacerbates pneumonia caused by commensal oral streptococci by inducing neutrophilic dysfunction in mixed infection. Products of type IX secretion system should be investigated as novel targets independent of reported virulence factors.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153328","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}
引用次数: 0
Improving Molecular Epidemiological Surveillance of Strongyloidiasis Upon Differentiation of Strongyloides fuelleborni fuelleborni From Strongyloides stercoralis. 从粪类圆线虫与燃料类圆线虫鉴别改进类圆线虫病分子流行病学监测。
The Journal of Infectious Diseases Pub Date : 2025-05-27 DOI: 10.1093/infdis/jiaf237
Lucas J Cunningham,William D Nevin,Jaco J Verweij,Dora Buonfrate,Salvatore Scarso,Virak Khieu,Angus M O'Ferrall,Sarah Rollason,J Russell Stothard
{"title":"Improving Molecular Epidemiological Surveillance of Strongyloidiasis Upon Differentiation of Strongyloides fuelleborni fuelleborni From Strongyloides stercoralis.","authors":"Lucas J Cunningham,William D Nevin,Jaco J Verweij,Dora Buonfrate,Salvatore Scarso,Virak Khieu,Angus M O'Ferrall,Sarah Rollason,J Russell Stothard","doi":"10.1093/infdis/jiaf237","DOIUrl":"https://doi.org/10.1093/infdis/jiaf237","url":null,"abstract":"Molecular epidemiological surveillance for zoonotic strongyloidiasis is confounded by a genus-specific TaqMan probe assay that conflates Strongyloides fuelleborni fuelleborni with Strongyloides stercoralis. To improve surveillance, we developed and validated a novel duplex species-specific TaqMan probe assay, screening a representative collection of available clinical samples. Our assay was highly discriminatory, evidencing no cross-reactivity, and had a lowest DNA detection limit of 1 pg/µL. However, as the genus-specific DNA assay has greater detection ability, we propose a 2-step protocol where samples are first screened with this assay then, if positive, screened with our species-specific assay, discriminating (co)infections between each threadworm species.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"51 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144146181","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}
引用次数: 0
Herpes simplex virus (HSV) neurovirulence across the human lifespan 单纯疱疹病毒(HSV)贯穿人类一生的神经毒力
The Journal of Infectious Diseases Pub Date : 2025-05-26 DOI: 10.1093/infdis/jiaf275
A Dutton, C K Hayes, D A Leib, L N Akhtar
{"title":"Herpes simplex virus (HSV) neurovirulence across the human lifespan","authors":"A Dutton, C K Hayes, D A Leib, L N Akhtar","doi":"10.1093/infdis/jiaf275","DOIUrl":"https://doi.org/10.1093/infdis/jiaf275","url":null,"abstract":"The ability of herpes simplex virus (HSV) to establish lifelong latency in sensory neurons makes it one of the most pervasive viruses worldwide. Although most HSV infections are asymptomatic or cause limited cutaneous symptoms, some give rise to serious central nervous system (CNS) manifestations. Both primary HSV infection and subsequent reactivation events can cause viral replication and spread within the brain, ultimately leading to pathologic inflammation and direct CNS damage. In addition to fulminant presentations of HSV encephalitis, subclinical HSV CNS infections have been implicated in neurodevelopmental, cognitive, and neurodegenerative impairment. Here, we review the pathogenesis of HSV infection and resulting CNS manifestations across the human lifespan. Identifying the mechanisms of HSV-induced CNS damage, and therefore the populations at highest risk for neurological morbidity, may provide a better understanding of the role viruses play in neurological diseases and inform novel approaches to treatment.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145636","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}
引用次数: 0
Evaluating the diagnostic utility of 16S ONT Sequencing in patients with Central Nervous System infections and its usefulness in Antimicrobial Stewardship 评估16S ONT测序在中枢神经系统感染患者中的诊断效用及其在抗菌药物管理中的用途
The Journal of Infectious Diseases Pub Date : 2025-05-24 DOI: 10.1093/infdis/jiaf280
Do Van Dong, Le Thi Kieu Linh, Nguyen Thi Tuyet Nga, Nghiem Xuan Hoan, Nguyen Thi Khanh Linh, Tran Thi Thanh Huyen, Hoang Xuan Quang, Tran Thi Lien, Van Dinh Trang, Vu Viet Sang, Peter G Kremsner, Le Huu Song, Dennis Nurjadi, Thirumalaisamy P Velavan
{"title":"Evaluating the diagnostic utility of 16S ONT Sequencing in patients with Central Nervous System infections and its usefulness in Antimicrobial Stewardship","authors":"Do Van Dong, Le Thi Kieu Linh, Nguyen Thi Tuyet Nga, Nghiem Xuan Hoan, Nguyen Thi Khanh Linh, Tran Thi Thanh Huyen, Hoang Xuan Quang, Tran Thi Lien, Van Dinh Trang, Vu Viet Sang, Peter G Kremsner, Le Huu Song, Dennis Nurjadi, Thirumalaisamy P Velavan","doi":"10.1093/infdis/jiaf280","DOIUrl":"https://doi.org/10.1093/infdis/jiaf280","url":null,"abstract":"Background Central nervous system (CNS) infections pose a significant public health challenge in resource-limited settings. Traditional culture-based and targeted molecular diagnostic methods have limitations in sensitivity and speed. This study retrospectively analysed the data and CSF samples from our previous study to assess the diagnostic efficacy of untargeted 16S ONT sequencing compared to conventional CSF culture methods, with the goal of improving diagnostic accuracy, reducing time to treatment, and enhancing patient outcomes. Material and Methods A total of 329 patients from four hospitals were enrolled in the study. CSF samples were collected and processed for both CSF culture and 16S ONT sequencing. DNA was extracted from CSF and amplified for 16S rRNA sequencing using the MinION platform. Descriptive analyses were conducted to assess pathogen detection rates and the potential impact of sequencing on antimicrobial stewardship. Results Of the 329 samples, 40 (12%) were positive for bacterial or fungal pathogens. 16S ONT detected pathogens in 28 samples (9%), while CSF culture identified pathogens in 23 samples (7%). 16S ONT sequencing identified 17 pathogens not detected by CSF culture, including Streptococcus suis and Acinetobacter baumannii. Based on 16S ONT findings, 61% of patients found to have received inappropriate empirical antibiotic therapy and could have benefited from improved antimicrobial management, including de-escalation in 11, escalation in five and adjustments in two cases. Conclusion 16S ONT sequencing showed higher sensitivity and diagnostic yield than CSF culture, providing clinical insights for managing CNS infections through targeted antibiotic use and enhanced antimicrobial stewardship in resource-limited settings.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145638","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}
引用次数: 0
Plasma lipid metabolites differentiate metabolic from viral chronic liver disease. 血浆脂质代谢物区分代谢性和病毒性慢性肝病。
The Journal of Infectious Diseases Pub Date : 2025-05-23 DOI: 10.1093/infdis/jiaf270
Kara Wegermann,Joseph E Lucas,Laura Dubois,Rebecca Mangus,Zhong Li,Cynthia A Moylan,Keyur Patel,Susanna Naggie
{"title":"Plasma lipid metabolites differentiate metabolic from viral chronic liver disease.","authors":"Kara Wegermann,Joseph E Lucas,Laura Dubois,Rebecca Mangus,Zhong Li,Cynthia A Moylan,Keyur Patel,Susanna Naggie","doi":"10.1093/infdis/jiaf270","DOIUrl":"https://doi.org/10.1093/infdis/jiaf270","url":null,"abstract":"BACKGROUND AND AIMLipid metabolism is altered in human immunodeficiency virus (HIV) infection and chronic liver diseases, but common and unique pathways have not been elucidated, limiting prevention and treatment strategies. The aim of this study was to discover lipid metabolite signatures for persons with HIV (PWH), PWH with HCV coinfection (PWH-HCV), and individuals with metabolic dysfunction-associated steatotic liver disease and steatohepatitis (MASLD, MASH).METHODSPlasma metabolite profiling was performed in adult participants in five cohorts from a single center: PWH (N = 50), PWH-HCV (N = 50), HIV-negative biopsy-proven MASLD (N = 46) and MASH (N = 50), and controls without HIV or chronic liver disease (N = 29). Plasma metabolites were assessed using Biocrates Q500, Bile Acid, and oxylipin assays. Latent factor analysis along with unadjusted and adjusted logistic regression models were performed. Significance was defined as p-value < 0.05 and false discovery rate (FDR) < 0.10.RESULTSCompared to controls, 457 of 816 measured metabolites were detected at different levels in PWH, 352 in PWH-HCV, 466 in MASLD, and 487 in MASH. Triglycerides and oxylipins were increased across disease states, but to a higher degree in PWH. PWH-HCV had a distinct metabolite signature with decreased ceramides and sphingomyelins. Levels of bile acid, amino acid, and fatty acid metabolites also differentiated cohorts.CONCLUSIONSLipid metabolites demonstrated pathways common to, and unique to, HIV, HCV, and MASLD. Further studies will hopefully reveal the pathogenic role of these metabolites in liver disease severity, particularly in PWH with steatotic liver disease.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"97 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122299","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}
引用次数: 0
Mind the clinic-community gap: how concerned should we be about false positive test results in mass tuberculosis screening? 注意临床与社区之间的差距:我们应该如何关注大规模结核病筛查中的假阳性检测结果?
The Journal of Infectious Diseases Pub Date : 2025-05-23 DOI: 10.1093/infdis/jiaf268
Lara D Veeken, Alvaro Schwalb, Katherine C Horton, Raspati C Koesoemadinata, Bachti Alisjahbana, Reinout van Crevel, Rein M G J Houben
{"title":"Mind the clinic-community gap: how concerned should we be about false positive test results in mass tuberculosis screening?","authors":"Lara D Veeken, Alvaro Schwalb, Katherine C Horton, Raspati C Koesoemadinata, Bachti Alisjahbana, Reinout van Crevel, Rein M G J Houben","doi":"10.1093/infdis/jiaf268","DOIUrl":"https://doi.org/10.1093/infdis/jiaf268","url":null,"abstract":"Community-wide screening for bacteriologically confirmed pulmonary tuberculosis may reduce tuberculosis burden, although concerns of overtreatment remain because of false positive diagnoses due to subpar specificity of current bacteriological tests for screening. Our review and data analysis shows that clinic-based test specificity estimates of Xpert against culture underestimate performance in communities, both for Xpert MTB/RIF (community=99.8% vs clinic=98.4%) and Xpert Ultra (community=99.4% vs clinic=95.6%), reducing the presumed false positivity of sputum Xpert using culture as reference by 86.8% and 85.4%, respectively, as compared to clinic-based specificity estimates. These findings support large-scale evaluation of community-wide screening for tuberculosis.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144130392","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}
引用次数: 0
Functional humoral response during intranasal convalescent plasma prophylaxis for SARS-CoV-2 SARS-CoV-2恢复期鼻内血浆预防期间的功能性体液反应
The Journal of Infectious Diseases Pub Date : 2025-05-23 DOI: 10.1093/infdis/jiaf273
Caro Verbrugghe, Rana Abdelnabi, Tania Maes, Birgit Weynand, Philippe Vandekerckhove, Johan Neyts, Hendrik B Feys, Elise Wouters
{"title":"Functional humoral response during intranasal convalescent plasma prophylaxis for SARS-CoV-2","authors":"Caro Verbrugghe, Rana Abdelnabi, Tania Maes, Birgit Weynand, Philippe Vandekerckhove, Johan Neyts, Hendrik B Feys, Elise Wouters","doi":"10.1093/infdis/jiaf273","DOIUrl":"https://doi.org/10.1093/infdis/jiaf273","url":null,"abstract":"Background The coronavirus disease 2019 (COVID-19) pandemic has had a profound global impact. Therapeutic strategies to bridge the crucial ‘lockdown’ timespan between the emergence of a new virus and vaccine rollout are needed. Methods We recently demonstrated that intranasal (i.n.) administration of COVID-19 convalescent plasma (CCP) in sentinel hamsters can limit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission from acutely infected index littermates. The current study investigates if functional immunity develops during i.n. prophylaxis in the same model. Results Lung tissue was free from infectious virus and pneumonia in sentinel hamsters after i.n. CCP prophylaxis, unlike those receiving non-immune control plasma (NIP). However, throat swabs from both groups contained viral RNA similar to intentionally infected index littermates. Anti-receptor binding domain (RBD) antibodies were detected in plasma from both sentinel groups two days after it showed in index littermates. This immune response was functional because all sentinel hamsters were protected from reinfection by the same viral strain. Conclusion Our findings demonstrate that i.n. CCP prophylaxis prevents lung disease in hamsters by restraining the infection to the upper respiratory tract, while still promoting a functional humoral immune response that protects against reinfection.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"131 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144130394","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}
引用次数: 0
Escherichia coli Type III Secretion System 2 (ETT2) is Associated with Patient Mortality in Bloodstream Infections. 大肠杆菌III型分泌系统2 (ETT2)与血液感染患者死亡率相关
The Journal of Infectious Diseases Pub Date : 2025-05-22 DOI: 10.1093/infdis/jiaf265
Joshua T Thaden,Phillip Cox,Paa Kwesi Ankrah,Sanjay Khandelwal,Jeffrey S Bourgeois,Orianna Poteete,Felicia Ruffin,Gowthami Arepally,Granger Sutton,Lauren Brinkac,Thomas H Clarke,Dennis C Ko,Derrick E Fouts,Vance G Fowler
{"title":"Escherichia coli Type III Secretion System 2 (ETT2) is Associated with Patient Mortality in Bloodstream Infections.","authors":"Joshua T Thaden,Phillip Cox,Paa Kwesi Ankrah,Sanjay Khandelwal,Jeffrey S Bourgeois,Orianna Poteete,Felicia Ruffin,Gowthami Arepally,Granger Sutton,Lauren Brinkac,Thomas H Clarke,Dennis C Ko,Derrick E Fouts,Vance G Fowler","doi":"10.1093/infdis/jiaf265","DOIUrl":"https://doi.org/10.1093/infdis/jiaf265","url":null,"abstract":"BACKGROUNDEscherichia coli has an extensive accessory genome, though its role in impacting patient mortality is unknown.METHODSWe performed whole genome sequencing with E. coli bloodstream infection isolates from inpatients at Duke University. Pan-genome analysis was used to identify flexible genomic islands associated with in-hospital attributable mortality (death due to infection). The functions of the flexible genomic islands of interest were investigated with serum growth assays and bacterial-host cell interaction assays.RESULTSWe included 193 E. coli genomes. Two separate genomic islands were co-present within 41 (21%) E. coli isolates and associated with increased attributable mortality (22% [9/41]) vs. 11% [17/152]) in an adjusted analysis (Mortality odds ratio 3.0; 95% confidence interval 1.1-7.9; p=0.03). The two genomic islands together contain genes homologous to a type III secretion system (T3SS): 1) E. coli type III secretion system 2 (ETT2), encoding 35 genes homologous to a T3SS basal body and needle complex, and 2) an ETT2 accessory region (ETT2-AR) encoding six genes homologous to a T3SS needle tip, translocases, and adhesin. ETT2/ETT2-AR altered bacterial virulence through two mechanisms. First, ETT2/ETT2-AR increased resistance to complement-mediated growth restriction by inhibiting classical complement pathway activation. Second, ETT2/ETT2-AR influenced E. coli-host cell interactions by increasing adhesion to and death of mammalian cells.CONCLUSIONSGenomic islands ETT2 and ETT2-AR are homologous to a T3SS, co-localize within specific E. coli lineages, associate with increased mortality in patients with E. coli bloodstream infection, and increase bacterial virulence through resistance to complement and enhanced host cell adhesion and death.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122301","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}
引用次数: 0
The Cost of Silence: A Call to Protect the Future of HIV Research and Care. 沉默的代价:呼吁保护艾滋病毒研究和护理的未来。
The Journal of Infectious Diseases Pub Date : 2025-05-22 DOI: 10.1093/infdis/jiaf267
Loreen Willenberg,William Freshwater,Dawn Averitt,Linda H Scruggs,Marc C E Wagner,Waheedah Shabazz-El,Wanda L London,Paul A Edmonds,Christopher Tunstall,Benedict Sandile Khumalo,Sharon Worth-Hatlee,Orbit Clanton,Derrick Mapp,David Palm,Michael Jentes,Susan Dickerson,Andy Kaytes,Jeff Taylor
{"title":"The Cost of Silence: A Call to Protect the Future of HIV Research and Care.","authors":"Loreen Willenberg,William Freshwater,Dawn Averitt,Linda H Scruggs,Marc C E Wagner,Waheedah Shabazz-El,Wanda L London,Paul A Edmonds,Christopher Tunstall,Benedict Sandile Khumalo,Sharon Worth-Hatlee,Orbit Clanton,Derrick Mapp,David Palm,Michael Jentes,Susan Dickerson,Andy Kaytes,Jeff Taylor","doi":"10.1093/infdis/jiaf267","DOIUrl":"https://doi.org/10.1093/infdis/jiaf267","url":null,"abstract":"","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"60 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122302","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}
引用次数: 0
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