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Correction. 修正。
IF 7.5 2区 医学 Q1 IMMUNOLOGY Pub Date : 2026-12-01 Epub Date: 2025-12-28 DOI: 10.1080/22221751.2025.2609512
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引用次数: 0
Global molecular epidemiology of Mycoplasma pneumoniae and its association with macrolide resistance and disease severity: a systematic review and meta-analysis. 肺炎支原体的全球分子流行病学及其与大环内酯耐药和疾病严重程度的关系:一项系统综述和荟萃分析
IF 13.2 2区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-16 DOI: 10.1080/22221751.2026.2614742
Xinyue Zhu,Yuyi Tang,Karen Spruyt,Janne Estill,Ivan D Florez,Yasser Sami Amer,Akihiko Ozaki,Yaolong Chen,Enmei Liu
The global molecular epidemiology of Mycoplasma pneumoniae (MP) and its associations with macrolide resistance and disease severity remain unclear. Studies reporting MP genotypes distribution by P1 typing, multiple locus variable number tandem repeat analysis (MLVA), or multilocus sequence typing analysis (MLST) among MP-infected patients were included. Data quality was assessed using the Joanna Briggs Institute tool and the Newcastle-Ottawa scale. Random-effects models were used to calculate pooled proportions of each MP genotype, with subgroup analyses by geographic region, age group, sex, time period, specimen type, and test assay. The proportions of macrolide-resistant MP and severe MP pneumonia cases were also evaluated. A total of 116 studies met the criteria. Predominant genotypes were P1-1 by P1 typing and 4572 by MLVA in the Western Pacific region and European region, and ST3 by MLST in the Western Pacific region. The proportions of P1-1 and 4572 were higher in the Western Pacific region than in other regions, and in children than in adults, whereas P1-2 and 3562 were opposite. Genotype dominance cycled between P1-1 and P1-2, and between 4572 and 3662. Macrolide resistance rates were highest in P1-1, 4572, and ST3 genotypes. Based on the currently available data, no association was detected between P1 genotypes and disease severity, although the limited sample size restricted the statistical power of this analysis. This comprehensive analysis elucidates the global molecular epidemiology of MP, highlights its clinical implications, and underscores the need for ongoing molecular surveillance to guide management and control strategies.
肺炎支原体(MP)的全球分子流行病学及其与大环内酯类药物耐药性和疾病严重程度的关系尚不清楚。通过P1分型、多位点可变数串联重复分析(MLVA)或多位点序列分型分析(MLST)在MP感染患者中报道MP基因型分布的研究被纳入。数据质量使用乔安娜布里格斯研究所工具和纽卡斯尔-渥太华量表进行评估。随机效应模型用于计算每个MP基因型的合并比例,并按地理区域、年龄组、性别、时间段、标本类型和检测方法进行亚组分析。大环内酯耐药MP和严重MP肺炎病例的比例也进行了评估。总共有116项研究符合标准。西太平洋地区和欧洲地区主要基因型为P1分型P1-1型和MLVA分型4572型,西太平洋地区主要基因型为MLST分型ST3型。P1-1和4572的比例在西太平洋地区高于其他地区,儿童高于成人,而P1-2和3562的比例相反。基因型优势循环发生在P1-1 ~ P1-2, 4572 ~ 3662之间。P1-1、4572和ST3基因型大环内酯类药物耐药率最高。根据目前可获得的数据,尽管有限的样本量限制了该分析的统计效力,但未检测到P1基因型与疾病严重程度之间的关联。这项综合分析阐明了MP的全球分子流行病学,强调了其临床意义,并强调了持续进行分子监测以指导管理和控制策略的必要性。
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引用次数: 0
Myxovirus resistance protein A to differentiate between viral and non-viral respiratory infections in adults: a prospective study. 黏液病毒抗性蛋白A用于区分成人的病毒性和非病毒性呼吸道感染:一项前瞻性研究。
IF 13.2 2区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-16 DOI: 10.1080/22221751.2026.2614734
Mengwei Yan,Nengyong Wang,Liping Yang,Xiaoqi Zhang,Yong Zhang,Weixia Xuan,Xiaoju Zhang,Gang Liu,Herong Wang,Yao Qing,Yeming Wang,Bin Cao
OBJECTIVESTo assess the diagnostic utility of Myxovirus resistance protein A (MxA) in differentiating between viral and non-viral respiratory infections in adults.METHODSThis prospective, multicenter diagnostic accuracy study enrolled adults with acute respiratory infections (ARI) from outpatient and inpatient settings, alongside asymptomatic controls. Peripheral blood was collected for quantitative MxA measurement. Pathogen detection used targeted next-generation sequencing combined with conventional microbiological testing. Aetiological diagnoses were determined using standardized algorithms based on detected pathogens. The diagnostic accuracy of MxA for identifying viral ARIs was calculated.RESULTSAmong 518 ARI patients, 325 had viral pathogens detected, 131 had bacterial/fungal pathogens, and 62 had no pathogen detected. Median MxA levels were significantly higher in viral (123.6 ng/ml; interquartile range [IQR], 56.4-189.6) than bacterial/fungal infections (15.9 ng/ml; IQR, 9.9-38.1; Bonferroni test p < 0.001) and controls (n = 158; 8.2 ng/mL; IQR, <5.0-16.4; Bonferroni test p < .001). The area under the receiver operating characteristic curve (AUC) for differentiating viral from bacterial/fungal infections was 0.83 (95% confidence interval [CI], 0.79-0.87). At an optimal cutoff of 50 ng/ml, MxA yielded a sensitivity of 77.8% (95% CI, 73.3-82.4%) and a specificity of 80.2% (95% CI, 73.3-87.0%). MxA levels were also elevated in atypical bacterial infections (n = 22; 60.9 ng/mL; IQR, 23.4-114.8), with no significant difference from viral group (Bonferroni test p = 0.12). When atypical bacteria were excluded, the AUC for differentiating viral from non-viral infections was 0.80 (95% CI, 0.76-0.84).CONCLUSIONSMxA demonstrates high diagnostic accuracy in distinguishing between viral and non-viral respiratory infections in adults.
目的评价黏液病毒耐药蛋白A (MxA)在区分成人病毒性和非病毒性呼吸道感染中的诊断价值。方法:这项前瞻性、多中心诊断准确性研究纳入了门诊和住院的急性呼吸道感染(ARI)成人患者,以及无症状对照组。采集外周血定量测定MxA。病原体检测采用靶向新一代测序结合常规微生物检测。病原学诊断采用基于检测到的病原体的标准化算法。计算MxA对病毒性ARIs的诊断准确性。结果518例急性呼吸道感染患者中,病毒致病菌325例,细菌/真菌致病菌131例,未检出致病菌62例。病毒组中位MxA水平(123.6 ng/ml,四分位间距[IQR], 56.4 ~ 189.6)显著高于细菌/真菌感染组(15.9 ng/ml, IQR, 9.9 ~ 38.1, Bonferroni检验p < 0.001)和对照组(n = 158, 8.2 ng/ml, IQR, <5.0 ~ 16.4, Bonferroni检验p < 0.001)。区分病毒感染和细菌/真菌感染的受试者工作特征曲线下面积(AUC)为0.83(95%可信区间[CI], 0.79-0.87)。在最佳截止值为50 ng/ml时,MxA的灵敏度为77.8% (95% CI, 73.3-82.4%),特异性为80.2% (95% CI, 73.3-87.0%)。非典型细菌感染组MxA水平也升高(n = 22; 60.9 ng/mL; IQR, 23.4-114.8),与病毒组无显著差异(Bonferroni检验p = 0.12)。当排除非典型细菌时,区分病毒感染和非病毒感染的AUC为0.80 (95% CI, 0.76-0.84)。结论smxa对成人病毒性和非病毒性呼吸道感染具有较高的诊断准确性。
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引用次数: 0
Modulating Chikungunya and Mayaro virus-induced disease severity in mice using low concentrations of anti-IFNAR1 antibodies. 使用低浓度的抗ifnar1抗体调节基孔肯雅和马雅罗病毒诱导的小鼠疾病严重程度
IF 13.2 2区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-14 DOI: 10.1080/22221751.2025.2611479
Konrad Wesselmann,Léa Luciani,Gregory Moureau,Jean-Selim Driouich,Ornellie Bernadin,Magali Gilles,Xavier de Lamballerie,Antoine Nougairède
The laboratory mouse (Mus musculus) is the most widely used animal model for preclinical research, with numerous wild-type and genetically modified mouse strains available. Chikungunya virus (CHIKV), a mosquito-borne arthritogenic alphavirus, has emerged in various new regions and caused several millions of cases within the last decade. Mayaro virus (MAYV), an arthritogenic alphaviruses closely related to CHIKV, remains geographically restricted to the Americas. Existing mouse models rely on immunodeficient mice, leading to lethal illness, or footpad injection, which induces localized arthropathy. We present a proof-of-concept study demonstrating how disease severity in mice can be modulated using sub-neutralizing concentrations of an interferon 1 receptor (IFNAR1) blocking monoclonal antibody (mAb). C57BL/6 mice were injected intraperitoneally with varying anti-IFNAR1 antibody doses before intraperitoneal infection with CHIKV or MAYV. For both, CHIKV and MAYV, we observed an anti-IFNAR1 mAb dose-dependent increase in blood viral loads and disease severity. A 1mg dose induced severe disease, whereas a 0.1 mg dose resulted in moderate symptoms in mice, mainly facial pain expression signs, accompanied by detectable viremia in the days preceding symptom onset. Viral loads in organs and serum concentrations of inflammatory cytokines and chemokines were also elevated in mice receiving 0.1mg anti-IFNAR1 mAb. In conclusion, we provide proof of concept that CHIKV and MAYV disease severity can be modulated using low concentrations of anti-IFNAR1 mAb. We used this approach to develop a new infection model for mild systemic disease, based on an accessible strain and a commercial antibody allowing for easy implementation and adaptation.
实验室小鼠(小家鼠)是临床前研究中最广泛使用的动物模型,有许多野生型和转基因小鼠品系。基孔肯雅病毒(CHIKV)是一种蚊子传播的致关节炎的甲病毒,在过去十年中在许多新的地区出现并造成数百万病例。马雅罗病毒(MAYV)是一种与CHIKV密切相关的致关节炎甲病毒,在地理上仍然局限于美洲。现有的小鼠模型依赖于导致致命疾病的免疫缺陷小鼠,或脚垫注射,导致局部关节病变。我们提出了一项概念验证研究,展示了如何使用亚中和浓度的干扰素1受体(IFNAR1)阻断单克隆抗体(mAb)来调节小鼠的疾病严重程度。在腹腔感染CHIKV或MAYV前,给C57BL/6小鼠注射不同剂量的抗ifnar1抗体。对于CHIKV和MAYV,我们观察到抗ifnar1单抗在血液病毒载量和疾病严重程度上的剂量依赖性增加。1mg剂量引起严重疾病,而0.1 mg剂量在小鼠中引起中度症状,主要是面部疼痛表达体征,并在症状发作前几天伴有可检测到的病毒血症。在接受0.1mg抗ifnar1单抗的小鼠中,器官中的病毒载量和血清中炎症细胞因子和趋化因子的浓度也升高。总之,我们提供了概念证明,CHIKV和MAYV疾病严重程度可以使用低浓度的抗ifnar1单抗来调节。我们使用这种方法开发了一种针对轻度全身性疾病的新感染模型,该模型基于一种可获得的菌株和一种易于实施和适应的商业抗体。
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引用次数: 0
Astrovirus and norovirus infections and their association with diarrheal symptoms in immunocompromised children. 免疫功能低下儿童星状病毒和诺如病毒感染及其与腹泻症状的关系
IF 13.2 2区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-13 DOI: 10.1080/22221751.2026.2616946
Amy E Davis,Yin Su,Ronald Dallas,Pamela Freiden,Janet A Englund,Eileen J Klein,Hana Hakim,Randall Hayden,Gabriela Maron,Elisa Margolis,Li Tang,Valerie Cortez,Stacey Schultz-Cherry
Human astroviruses are a common cause of viral gastroenteritis and are often underdiagnosed. While infections are typically mild or asymptomatic in immunocompetent hosts, astrovirus can cause prolonged and severe disease in immunocompromised individuals. Here, we conducted a case-control study to evaluate the clinical presentation of astrovirus infections in pediatric oncology patients. Our findings were compared to two groups: (1) norovirus infections in the same immunocompromised cohort, and (2) a cohort of immunocompetent children with and without diarrheal symptoms. Astrovirus was detected in 9.8% of immunocompromised patients, with prolonged shedding seen in multiple cases. Astrovirus infection was associated with an increased odds of diarrhea, although this association weakened when adjusting for co-infections. In contrast, norovirus was not significantly associated with diarrhea in immunocompromised patients, despite prolonged shedding in 24% of the cohort. High rates of co-infection with adenovirus and Clostridium difficile may have influenced symptom patterns. In the immunocompetent cohort, astrovirus was not associated with diarrhea, while norovirus showed a strong association with symptoms. These findings indicate that astrovirus infections are more likely to cause diarrhea in immunocompromised pediatric patients, while often asymptomatic in immunocompetent children. Norovirus showed the opposite trend, highlighting distinct roles of host immune status in shaping clinical outcomes. These findings highlight the importance of considering astrovirus as a potential contributor to gastrointestinal symptoms in immunocompromised children and call for broader diagnostic testing and further research on viral co-infections and persistence.
人类星状病毒是病毒性肠胃炎的常见病因,但常常未得到充分诊断。虽然在免疫正常的宿主中感染通常是轻微或无症状的,但在免疫功能低下的个体中,星状病毒可引起长期和严重的疾病。在这里,我们进行了一项病例对照研究,以评估儿科肿瘤患者的星状病毒感染的临床表现。我们的研究结果与两组进行了比较:(1)同一免疫功能低下队列中的诺如病毒感染;(2)有或无腹泻症状的免疫功能正常儿童队列。在9.8%的免疫功能低下患者中检测到星状病毒,在多例患者中观察到长时间的脱落。星状病毒感染与腹泻的几率增加有关,尽管在调整合并感染时这种关联减弱了。相比之下,诺如病毒与免疫功能低下患者的腹泻没有显著相关性,尽管在24%的队列中有长时间的脱落。腺病毒和艰难梭菌合并感染的高发生率可能影响了症状模式。在免疫功能正常的队列中,星状病毒与腹泻无关,而诺如病毒与症状密切相关。这些发现表明,星状病毒感染在免疫功能低下的儿童患者中更容易引起腹泻,而在免疫功能正常的儿童中通常无症状。诺如病毒表现出相反的趋势,突出了宿主免疫状态在塑造临床结果中的独特作用。这些发现强调了考虑星状病毒作为免疫功能低下儿童胃肠道症状的潜在因素的重要性,并呼吁进行更广泛的诊断测试和进一步研究病毒合并感染和持久性。
{"title":"Astrovirus and norovirus infections and their association with diarrheal symptoms in immunocompromised children.","authors":"Amy E Davis,Yin Su,Ronald Dallas,Pamela Freiden,Janet A Englund,Eileen J Klein,Hana Hakim,Randall Hayden,Gabriela Maron,Elisa Margolis,Li Tang,Valerie Cortez,Stacey Schultz-Cherry","doi":"10.1080/22221751.2026.2616946","DOIUrl":"https://doi.org/10.1080/22221751.2026.2616946","url":null,"abstract":"Human astroviruses are a common cause of viral gastroenteritis and are often underdiagnosed. While infections are typically mild or asymptomatic in immunocompetent hosts, astrovirus can cause prolonged and severe disease in immunocompromised individuals. Here, we conducted a case-control study to evaluate the clinical presentation of astrovirus infections in pediatric oncology patients. Our findings were compared to two groups: (1) norovirus infections in the same immunocompromised cohort, and (2) a cohort of immunocompetent children with and without diarrheal symptoms. Astrovirus was detected in 9.8% of immunocompromised patients, with prolonged shedding seen in multiple cases. Astrovirus infection was associated with an increased odds of diarrhea, although this association weakened when adjusting for co-infections. In contrast, norovirus was not significantly associated with diarrhea in immunocompromised patients, despite prolonged shedding in 24% of the cohort. High rates of co-infection with adenovirus and Clostridium difficile may have influenced symptom patterns. In the immunocompetent cohort, astrovirus was not associated with diarrhea, while norovirus showed a strong association with symptoms. These findings indicate that astrovirus infections are more likely to cause diarrhea in immunocompromised pediatric patients, while often asymptomatic in immunocompetent children. Norovirus showed the opposite trend, highlighting distinct roles of host immune status in shaping clinical outcomes. These findings highlight the importance of considering astrovirus as a potential contributor to gastrointestinal symptoms in immunocompromised children and call for broader diagnostic testing and further research on viral co-infections and persistence.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"10 1","pages":"2616946"},"PeriodicalIF":13.2,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956091","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
HIV expression persists in the cerebrospinal fluid of HIV-associated neurocognitive disorders despite effective ART. 尽管抗逆转录病毒治疗有效,但艾滋病毒相关神经认知障碍患者的脑脊液中仍存在艾滋病毒表达。
IF 13.2 2区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-13 DOI: 10.1080/22221751.2026.2616945
Gabriela S Prates,Xiaoyi Li,Victor Folgosi,Ciniso S Shabangu,George G Souza,Carlos Apoliano,Maria R Gascon,Mariana A Monteiro,Carolina Gualqui,Rosangela Santos Eichler,Helio Gomes,Nikesh Katuwal,Cassandra Gilbert,Yuyang Tang,Jorge Casseb,Guochun Jiang
Despite effective antiretroviral therapy (ART), HIV-associated neurocognitive disorders (HAND) persist in people with HIV (PWH). The central nervous system (CNS) may act as a viral reservoir due to limited ART penetration and virological discordance between plasma and cerebrospinal fluid (CSF). In a cross-sectional study of 24 ART-treated PWH, participants were stratified as cognitively normal (CN, n = 10) or HAND (n = 14), including asymptomatic neurocognitive impairment (ANI, n = 3), mild neurocognitive disorder (MND, n = 9), and HIV-associated dementia (HAD, n = 2). HIV RNA was quantified in paired plasma and CSF by RT-ddPCR. CSF peptidome profiling was performed using mass spectrometry, and ART concentrations were measured by LC-MS/MS. HIV infectivity in CSF was assessed via viral outgrowth assays. HIV RNA was undetectable in plasma but present in CSF from HAND participants, indicating compartmentalized viral persistence. Tenofovir and lamivudine levels were higher in plasma, whereas dolutegravir trended higher in CSF. Nevertheless, all CSF drug concentrations exceeded their IC50 values in effectively suppressing active HIV replication. Peptidomic analysis identified HIV-derived peptides (e.g., Env and Pol) exclusively in HAND samples, accompanied by an early reduction in β-tau. Although HIV RNA and peptides were detectable, no productive infection was established by CSF in permissive immune cells. Together, despite pharmacologically sufficient ART penetration, HIV persists in the CSF of PWH with HAND. These findings suggest that the latent HIV infection with non-replicative viral expression, rather than residual active HIV replication, may contribute to neuroinflammation and cognitive decline in PWH on suppressive ART.
尽管抗逆转录病毒治疗(ART)有效,HIV相关神经认知障碍(HAND)在HIV感染者(PWH)中持续存在。中枢神经系统(CNS)可能作为病毒库,由于有限的抗逆转录病毒药物渗透和血浆和脑脊液(CSF)之间的病毒学不一致。在一项针对24例接受art治疗的PWH患者的横断面研究中,参与者被分为认知正常(CN, n = 10)或HAND (n = 14),包括无症状神经认知障碍(ANI, n = 3)、轻度神经认知障碍(MND, n = 9)和hiv相关痴呆(HAD, n = 2)。采用RT-ddPCR定量检测配对血浆和脑脊液中的HIV RNA。采用质谱法进行脑脊液肽肽谱分析,采用LC-MS/MS法测定ART浓度。通过病毒生长试验评估脑脊液中HIV的感染性。HIV RNA在血浆中检测不到,但在HAND参与者的CSF中存在,表明病毒存在区隔性。替诺福韦和拉米夫定在血浆中的水平较高,而多替替韦在脑脊液中的水平趋于较高。然而,所有CSF药物浓度均超过其IC50值,有效抑制活跃的HIV复制。肽组学分析发现hiv衍生肽(例如,Env和Pol)仅在HAND样品中,伴随着β-tau的早期减少。虽然检测到HIV RNA和多肽,但CSF在允许免疫细胞中未建立生产性感染。总之,尽管抗逆转录病毒药物在药理学上有足够的渗透,但HIV仍然存在于患有HAND的PWH CSF中。这些发现表明,具有非复制性病毒表达的潜伏性HIV感染,而不是残留的活性HIV复制,可能导致PWH在抑制性抗逆转录病毒治疗中出现神经炎症和认知能力下降。
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引用次数: 0
A pbpB1 mutation causing reduced β-lactam susceptibility in clinical Listeria monocytogenes isolates. pbpB1突变导致临床单核增生李斯特菌分离株β-内酰胺敏感性降低。
IF 13.2 2区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-13 DOI: 10.1080/22221751.2026.2616949
Sabrina Wamp,Rosalyn Wagner,Franziska Schuler,Alexander Krüttgen,Antje Flieger,Sven Halbedel
Listeriosis is a severe foodborne infection and associated with high mortality. Treatment is based on ampicillin, amoxicillin or penicillin, often combined with gentamicin, but meropenem is also used occasionally. β-lactam resistant Listeria monocytogenes isolates are infrequently described but the mechanism of resistance is not known. A clinical L. monocytogenes isolate with reduced β-lactam susceptibility was collected from a German listeriosis patient. Resistance profiling, whole genome sequencing, comparative genomics and genetic experiments were used to identify the causative DNA polymorphism. A W428R substitution near the active site of penicillin binding protein B1 (PBPB1) was identified as the cause of reduced ampicillin, amoxicillin and meropenem susceptibility. Further clinical L. monocytogenes isolates with similar susceptibility profiles were found by searching the genome database of the German consultant laboratory for Listeria for pbpB1 W428R-positive isolates. Spontaneous suppressors of L. monocytogenes reference strain EGD-e with reduced β-lactam susceptibility were selected during ampicillin exposure and their genomes were sequenced. The same pbpB1 mutation emerged in strain EGD-e during cultivation in the presence of ampicillin. Further experiments showed that meropenem also promotes the development of resistant suppressor mutants with pbpB1 mutations. Our work demonstrates that β-lactam susceptibility of L. monocytogenes can be reduced through a specific substitution in PBPB1. This mutation is potentially selected for during β-lactam treatment.
李斯特菌病是一种严重的食源性感染,与高死亡率有关。治疗以氨苄西林、阿莫西林或青霉素为基础,通常与庆大霉素联合使用,但偶尔也使用美罗培南。对β-内酰胺耐药的单核增生李斯特菌分离株很少被报道,但其耐药机制尚不清楚。从德国李斯特菌病患者中分离出一株β-内酰胺敏感性降低的临床单核细胞增生乳杆菌。采用抗性谱分析、全基因组测序、比较基因组学和遗传实验等方法鉴定病原菌DNA多态性。青霉素结合蛋白B1 (PBPB1)活性位点附近的W428R取代被确定为氨苄西林、阿莫西林和美罗培南敏感性降低的原因。在德国李斯特菌咨询实验室基因组数据库中检索pbpB1 w428r阳性分离株,进一步发现具有相似敏感性的临床单核增生乳杆菌分离株。在氨苄西林暴露过程中,筛选单核增生乳杆菌β-内酰胺敏感性降低的EGD-e自发抑制菌,并对其基因组进行测序。菌株EGD-e在氨苄西林存在下的培养过程中出现了相同的pbpB1突变。进一步的实验表明,美罗培南也促进了pbpB1突变的耐药抑制突变体的发展。我们的研究表明,单核增生乳杆菌的β-内酰胺敏感性可以通过PBPB1的特异性取代而降低。这种突变可能在β-内酰胺处理期间被选择。
{"title":"A pbpB1 mutation causing reduced β-lactam susceptibility in clinical Listeria monocytogenes isolates.","authors":"Sabrina Wamp,Rosalyn Wagner,Franziska Schuler,Alexander Krüttgen,Antje Flieger,Sven Halbedel","doi":"10.1080/22221751.2026.2616949","DOIUrl":"https://doi.org/10.1080/22221751.2026.2616949","url":null,"abstract":"Listeriosis is a severe foodborne infection and associated with high mortality. Treatment is based on ampicillin, amoxicillin or penicillin, often combined with gentamicin, but meropenem is also used occasionally. β-lactam resistant Listeria monocytogenes isolates are infrequently described but the mechanism of resistance is not known. A clinical L. monocytogenes isolate with reduced β-lactam susceptibility was collected from a German listeriosis patient. Resistance profiling, whole genome sequencing, comparative genomics and genetic experiments were used to identify the causative DNA polymorphism. A W428R substitution near the active site of penicillin binding protein B1 (PBPB1) was identified as the cause of reduced ampicillin, amoxicillin and meropenem susceptibility. Further clinical L. monocytogenes isolates with similar susceptibility profiles were found by searching the genome database of the German consultant laboratory for Listeria for pbpB1 W428R-positive isolates. Spontaneous suppressors of L. monocytogenes reference strain EGD-e with reduced β-lactam susceptibility were selected during ampicillin exposure and their genomes were sequenced. The same pbpB1 mutation emerged in strain EGD-e during cultivation in the presence of ampicillin. Further experiments showed that meropenem also promotes the development of resistant suppressor mutants with pbpB1 mutations. Our work demonstrates that β-lactam susceptibility of L. monocytogenes can be reduced through a specific substitution in PBPB1. This mutation is potentially selected for during β-lactam treatment.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"45 1","pages":"2616949"},"PeriodicalIF":13.2,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956158","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
Community-based "X-ray+Xpert® MTB/RIF ultra pooling test" case-finding strategy among high-risk groups in rural areas: a prospective application study. 以社区为基础的“x射线+Xpert®MTB/RIF超汇集试验”在农村地区高危人群中的病例发现策略:一项前瞻性应用研究。
IF 13.2 2区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-12 DOI: 10.1080/22221751.2025.2610857
Zhengwei Liu,Ruiqi Chen,Bing Li,Junhang Pan,Bowen Xie,Qi Wu,Xinghui Gao,Mingwu Zhang,Yelei Zhu,Kunyang Wu,Haiting Chen,David H Persing,Yi-Wei Tang,Bin Chen,Qingrong Zhou,Jianmin Jiang
Active case-finding (ACF) strategies for tuberculosis (TB) in high-incidence rural areas require cost-effective solutions. We evaluated a novel community-based ACF strategy integrating pooled sputum molecular testing via Xpert® MTB/RIF Ultra. A prospective study was conducted in three high-TB-incidence rural townships in Zhejiang, China (2024). Residents aged ≥65 years underwent centralized health check-ups, including chest X-rays (CXR). Sputum samples from eight consecutive individuals with abnormal CXR findings were pooled for Xpert® MTB/RIF Ultra testing. Positive pools prompted individual retesting. Participants with positive individual test results were referred to designated hospitals for standardized treatment. Among 16,558 eligible residents, 6,960 (42.0%) participated. CXR abnormalities were detected in 1,912 participants (27.5%), with 1,883 providing sputum samples. Pooled testing identified 32 bacteriologically confirmed TB cases among 1,883 participants with CXR abnormalities, yielding a detection rate of 1.7%. The number needed to screen (NNS) to identify one case was 218, which was 177 fewer than that required by the chest X-ray-based alone active case finding strategy. Screening yields of newly detected TB through ACF was 0.460%. The innovative strategy reduced per-case screening costs to US$4.37 (vs. US$54.78 for individual testing) and per-confirmed-case cost to US$949.49. Integrating a pooled Xpert® MTB/RIF Ultra testing with routine health check-ups provides a high-yield, cost-effective ACF strategy for detecting active TB in high-risk elderly populations in rural settings. This approach addresses key barriers to scalable community-based screening.
在高发病率的农村地区,结核病的主动病例发现战略需要具有成本效益的解决方案。我们评估了一种新的基于社区的ACF策略,该策略通过Xpert®MTB/RIF Ultra整合了痰分子检测。在浙江省三个结核病高发乡镇进行前瞻性研究(2024年)。年龄≥65岁的居民接受集中健康检查,包括胸部x光检查(CXR)。连续8例CXR异常患者的痰样本被合并用于Xpert®MTB/RIF Ultra检测。阳性池促使个人重新检测。个体检测结果呈阳性的参与者被转诊到指定医院进行标准化治疗。在16558名符合条件的居民中,有6960人(42.0%)参加了调查。在1912名参与者(27.5%)中检测到CXR异常,其中1883名提供了痰样本。合并检测在1883名CXR异常的参与者中确定了32例细菌学证实的结核病病例,检出率为1.7%。需要筛查(NNS)以确定一个病例的人数为218人,比单独以胸部x线为基础的主动病例发现策略所需的人数少177人。ACF对新检结核的筛查率为0.60%。这一创新策略将每例筛查成本降至4.37美元(单独检测为54.78美元),每确诊病例成本降至949.49美元。将汇集的Xpert®MTB/RIF Ultra检测与常规健康检查相结合,为在农村地区高风险老年人群中检测活动性结核病提供了一种高产、具有成本效益的ACF策略。这种方法解决了可扩展的社区筛查的主要障碍。
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引用次数: 0
Live-attenuated African swine fever vaccine HLJ/18-7GD is safe in pregnant sows with no impact on reproductive performance or offspring health at a field farm 在田间农场,非洲猪瘟减毒活疫苗HLJ/18-7GD对怀孕母猪是安全的,对繁殖性能或后代健康没有影响
IF 13.2 2区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-08 DOI: 10.1080/22221751.2026.2614713
Jinxiong Liu, Leilei Ding, Weiye Chen, Dongming Zhao, Wenxing Liu, Yonggang Liu, Fang Li, Renqiang Liu, Hong Huo, Yuanmao Zhu, Hongliang Zhang, Huairan Liu, Zhijun Tian, Zhigao Bu
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引用次数: 0
Can we escape from top-priority ESKAPE pathogens? 我们能摆脱ESKAPE最重要的病原体吗?
IF 7.5 2区 医学 Q1 IMMUNOLOGY Pub Date : 2026-01-08 DOI: 10.1080/22221751.2026.2614739
Lingbing Zeng, YouJun Feng, Minggui Wang

The ESKAPE pathogens-Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.-are designated by the World Health Organization as critical-priority multidrug-resistant organisms. These bacteria are leading contributors to the global antimicrobial resistance crisis, significantly increasing morbidity, mortality, and healthcare costs worldwide. Their capacity to evade conventional antibiotics continues to complicate clinical management and undermine infection control efforts. Tackling the global threat of ESKAPE pathogens demands coordinated and sustained interventions. This mini review summarizes recent evidence on the burden and prevalence of ESKAPE infections and assesses emerging strategies to combat resistance. Progress in surveillance and promising preclinical and clinical studies of novel therapies underscore that integrated approaches are crucial. Moving forward, a balanced emphasis on prevention, surveillance, and therapeutic innovation will be essential to mitigating the threat posed by ESKAPE pathogens over the coming decade.

ESKAPE病原体——粪肠球菌、金黄色葡萄球菌、肺炎克雷伯菌、鲍曼不动杆菌、铜绿假单胞菌和肠杆菌——被世界卫生组织指定为重点多重耐药生物。这些细菌是造成全球抗菌素耐药性危机的主要原因,显著增加了全世界的发病率、死亡率和医疗费用。它们逃避常规抗生素的能力继续使临床管理复杂化,并破坏感染控制的努力。应对ESKAPE病原体的全球威胁需要协调和持续的干预措施。这篇小型综述总结了最近关于ESKAPE感染负担和流行的证据,并评估了对抗耐药性的新战略。在新疗法的监测和有希望的临床前和临床研究方面的进展强调了综合方法的重要性。展望未来,平衡地强调预防、监测和治疗创新对于在未来十年减轻ESKAPE病原体构成的威胁至关重要。
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引用次数: 0
期刊
Emerging Microbes & Infections
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