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Correlations between incidence of syphilis and frequencies of human leukocyte antigens haplotypes in China: An ecological study 中国梅毒发病率与人白细胞抗原单倍型频率的相关性:一项生态学研究。
IF 2.6 4区 医学 Q3 INFECTIOUS DISEASES Pub Date : 2025-11-19 DOI: 10.1016/j.meegid.2025.105854
Wei-Jing Lin , Hong-Fei Mi , Ning-Dai Chen , Yue Zhong , Tian-Ci Yang , Yao Xiao
In China, the incidence of syphilis varies across different regions, as do the frequencies of HLA haplotypes. The progression and stages of syphilis infection may be associated with HLA polymorphisms. This study employed an ecological study design, utilizing data from a nationwide survey on the distribution of HLA frequencies in the Chinese Bone Marrow Donor Program and the incidence of syphilis in China during the same period. Pearson and Spearman correlation analyses, adjusted for multiple testing using the Benjamini-Hochberg procedure, were performed to investigate the correlation between HLA polymorphism and the incidence of syphilis. The overall incidence of syphilis was significantly correlated with the frequencies of six specific HLA-A-C-B-DRB1-DQB1 haplotypes in China. Additionally, as many as 24 HLA-A-C-B-DRB1-DQB1 haplotypes were found to be correlated with the incidence of congenital syphilis. Nominal correlations were observed between several HLA haplotype frequencies and the incidences of secondary, tertiary, and latent syphilis prior to false discovery rate correction. These findings suggest that the frequencies of HLA haplotypes are correlated with the incidence of syphilis in China, particularly in congenital syphilis cases. Collectively, susceptibility to syphilis infection and disease progression appears to be closely linked to HLA polymorphisms.
在中国,梅毒的发病率在不同地区有所不同,HLA单倍型的频率也是如此。梅毒感染的进展和分期可能与HLA多态性有关。本研究采用了生态研究设计,利用了中国骨髓捐献计划中HLA频率分布和同期中国梅毒发病率的全国调查数据。Pearson和Spearman相关分析,使用Benjamini-Hochberg程序调整多重检验,以调查HLA多态性与梅毒发病率之间的相关性。中国梅毒总发病率与6种特异性HLA-A-C-B-DRB1-DQB1单倍型的频率显著相关。此外,发现多达24个HLA-A-C-B-DRB1-DQB1单倍型与先天性梅毒的发病率相关。在错误发现率校正之前,观察到几种HLA单倍型频率与继发性、三期和潜伏性梅毒发病率之间的名义相关性。这些发现表明,HLA单倍型的频率与中国梅毒的发病率相关,特别是在先天性梅毒病例中。总的来说,梅毒感染的易感性和疾病进展似乎与HLA多态性密切相关。
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引用次数: 0
Immunological role of IL-25 on gut-dwelling helminths IL-25对肠道蠕虫的免疫作用。
IF 2.6 4区 医学 Q3 INFECTIOUS DISEASES Pub Date : 2025-11-19 DOI: 10.1016/j.meegid.2025.105856
Gashaw Azanaw Amare , Yenesew Mihret Wondmagegn , Adane Adugna , Desalegn Abebaw , Abateneh Melkamu , Habtamu Belew , Zigale Hibstu Teffera , Mamaru Getinet , Mohammed Jemal , Temesgen Baylie , Deresse Sinamaw Asmare , Abebe Yenesew , Abebe Fenta , Mesafint Woreket , Abebaw Setegn , Birhanu Malede
Interleukin-25 (IL-25) is a crucial cytokine in coordinating type 2 immunity against gut-dwelling helminths. IL-25 is produced by a variety of cells, including epithelial and immune cells, and primarily stimulates Th2-type immune responses characterized by the release of IL-13, IL-5, and IL-4, which play a vital role in eosinophilia induction, goblet cell hyperplasia, and IgE synthesis. This review critically examines IL-25's role in maintaining intestinal barrier integrity and modulating regulatory immune responses. This review addresses how IL-25 integrates signals from the epithelial interface, immune cells, and gut microbiota to calibrate appropriate host defense while preventing pathological inflammation. Furthermore, this paper presents recent evidence supporting IL-25's therapeutic potential, both as a potential adjuvant therapy to enhance parasite clearance and as a modulator of inflammatory conditions where type 2 immunity proves deficient.
白细胞介素-25 (IL-25)是协调2型免疫对抗肠道蠕虫的关键细胞因子。IL-25由多种细胞产生,包括上皮细胞和免疫细胞,主要刺激以释放IL-13、IL-5和IL-4为特征的th2型免疫反应,在嗜酸性粒细胞诱导、杯状细胞增生和IgE合成中起重要作用。本文综述了IL-25在维持肠道屏障完整性和调节调节免疫反应中的作用。本文综述了IL-25如何整合来自上皮界面、免疫细胞和肠道微生物群的信号,以校准适当的宿主防御,同时预防病理性炎症。此外,本文提出了支持IL-25治疗潜力的最新证据,既可以作为增强寄生虫清除的潜在辅助治疗,也可以作为2型免疫缺陷的炎症条件的调节剂。
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引用次数: 0
Exploring the effect of the foodborne pathogen Bacillus cereus on the growth, immunity, and gut microbiota of mice 探讨食源性芽孢杆菌对小鼠生长、免疫和肠道菌群的影响
IF 2.6 4区 医学 Q3 INFECTIOUS DISEASES Pub Date : 2025-11-07 DOI: 10.1016/j.meegid.2025.105852
Xueqi Teng , Chengwen Song , Jing Hang
Bacillus cereus, a common spore-forming bacterium, is a major cause of foodborne illness worldwide. This study investigated its effects on mouse physiology and wellbeing—including body-weight trajectory, digestive/oxidative biochemistry, liver-based immune enzyme proxies, and the gut microbiota. Mice were given oral doses of B. cereus at concentrations ranging from 103 to 107 CFU/mL over seven days. Exposure resulted in acute physiological responses, including transient growth suppression, altered antioxidant enzyme activity (increased Total Antioxidant Capacity [T-AOC] and Superoxide Dismutase [SOD], decreased Lysozyme [LZM]), and reduced blood glucose and amylase levels, particularly at lower doses. These findings suggest immune disruption and metabolic imbalance. Gut microbiota analysis revealed marked compositional shifts, characterized by increased richness, a decreased Firmicutes/Bacteroidota ratio, enrichment of Akkermansia muciniphila, and a decline in beneficial genera such as Lactobacillus. Functional prediction indicated suppression of microbial pathways related to penicillin/cephalosporin biosynthesis. Collectively, these results indicate that short-term B. cereus exposure perturbs physiological status and the gut ecosystem, even at low doses, outlining potential subclinical risks of B. cereus contamination and implications for gut health and food safety.
蜡样芽孢杆菌是一种常见的孢子形成细菌,是世界范围内食源性疾病的主要原因。本研究探讨了其对小鼠生理和健康的影响,包括体重轨迹、消化/氧化生化、肝脏免疫酶代理和肠道微生物群。小鼠口服蜡样芽孢杆菌浓度为103 ~ 107 CFU/mL,持续7天。暴露导致急性生理反应,包括短暂的生长抑制,抗氧化酶活性改变(总抗氧化能力[T-AOC]和超氧化物歧化酶[SOD]增加,溶菌酶[LZM]降低),血糖和淀粉酶水平降低,特别是在低剂量下。这些发现表明免疫紊乱和代谢失衡。肠道菌群分析显示出明显的组成变化,其特征是丰富度增加,厚壁菌门/拟杆菌门比例下降,嗜粘杆菌(Akkermansia muciniphila)富集,而乳酸菌(Lactobacillus)等有益菌群减少。功能预测显示抑制与青霉素/头孢菌素生物合成相关的微生物途径。总之,这些结果表明,即使在低剂量下,短期蜡样芽孢杆菌暴露也会扰乱生理状态和肠道生态系统,概述了蜡样芽孢杆菌污染的潜在亚临床风险以及对肠道健康和食品安全的影响。
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引用次数: 0
Phylodynamic analysis of recent bovine viral diarrhea viruses in the Republic of Korea 韩国新近牛病毒性腹泻病毒的系统动力学分析。
IF 2.6 4区 医学 Q3 INFECTIOUS DISEASES Pub Date : 2025-11-04 DOI: 10.1016/j.meegid.2025.105851
Hyung-Chul Cho , Jaehyeok Song , Kyoung-Seong Choi
Bovine viral diarrhea virus (BVDV) is a globally distributed and economically significant viral pathogen in the cattle industry. Despite ongoing circulation, molecular evolutionary and phylodynamic data on BVDV in the Republic of Korea (ROK) remain limited. This study aimed to investigate the prevalence and subtype of recent BVDVs circulating in the ROK and to analyze their phylodynamic patterns. A total of 5286 samples, including serum, blood, and diarrheic feces, were collected from Korean native cattle between 2021 and 2022. Of these, 29.9 % (1584/5286) tested positive for BVDV by real-time RT-PCR targeting the 5′UTR. BVDV was most frequently detected in serum (36.9 %), followed by feces (12.3 %) and blood (9.6 %). Sequencing analysis identified three subtypes: BVDV-1a (16.5 %), BVDV-1b (53.6 %), and BVDV-2a (29.9 %). The maximum clade credibility (MCC) tree based on the 5′UTR indicated that the most recent common ancestors of BVDV-1 and BVDV-2 in the ROK likely emerged around 1988 and 1995, respectively. The evolutionary rates of BVDV-1 and BVDV-2a were estimated at 3.99 × 10−3 and 4.0 × 10−3 substitutions/site/year, respectively, indicating rapid evolution compared with those in other countries. The MCC tree revealed an evolutionary order of BVDV-1a, -2a, and -1b. Phylogenetic analysis showed that recent BVDV-1b sequences exhibited greater genetic variation than those of other subtypes, suggesting accelerated and heterogeneous evolutionary dynamics. Bayesian skyline plot analysis demonstrated a marked increase in the viral population of BVDV-1 (especially BVDV-1b) around 2018, while BVDV-2a exhibited a more gradual expansion beginning around 2016. This was the first study to characterize the evolutionary dynamics of BVDVs in the ROK. These findings enhance understanding of the recent molecular epidemiology and evolutionary dynamics of BVDV in the ROK and underscore the need for continued molecular surveillance and control strategies.
牛病毒性腹泻病毒(Bovine viral diarrhea virus, BVDV)是一种全球分布的、具有重要经济意义的养牛业病毒性病原体。尽管正在传播,但韩国BVDV的分子进化和系统动力学数据仍然有限。本研究旨在调查韩国最近流行的BVDVs的流行情况和亚型,并分析其系统动力学模式。从2021年到2022年,从韩国本土牛身上采集了血清、血液、腹泻粪便等5286份样本。其中,29.9 %(1584/5286)通过针对5'UTR的实时RT-PCR检测BVDV阳性。BVDV以血清(36.9 %)检出率最高,其次为粪便(12.3 %)和血液(9.6 %)。测序分析鉴定出三种亚型:BVDV-1a(16.5% %)、BVDV-1b(53.6 %)和BVDV-2a(29.9 %)。基于5′utr的最大进化枝可信度(MCC)树表明,韩国BVDV-1和BVDV-2最近的共同祖先可能分别出现在1988年和1995年左右。BVDV-1和BVDV-2a的进化速率分别为3.99 × 10-3和4.0 × 10-3个替换/位点/年,与其他国家相比进化速度较快。MCC树显示了BVDV-1a、-2a和-1b的进化顺序。系统发育分析表明,最近的BVDV-1b序列比其他亚型表现出更大的遗传变异,表明其进化动力学加速且异质性。贝叶斯天际线图分析显示,BVDV-1(尤其是BVDV-1b)的病毒数量在2018年左右显著增加,而BVDV-2a的病毒数量在2016年左右开始逐渐增加。这是第一个描述韩国BVDVs进化动力学的研究。这些发现加强了对韩国BVDV最近的分子流行病学和进化动力学的理解,并强调了继续进行分子监测和控制策略的必要性。
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引用次数: 0
Virulence comparison and pathological impacts of three clinical Klebsiella pneumoniae isolates in a zebrafish larval model 三种临床肺炎克雷伯菌分离株在斑马鱼幼虫模型中的毒力比较和病理影响
IF 2.6 4区 医学 Q3 INFECTIOUS DISEASES Pub Date : 2025-11-04 DOI: 10.1016/j.meegid.2025.105847
Yanfei Jing , Ke Yu , Hai-yan Yu , Pei-pei Zhao , Hui-fang Wang , Zhong-bo Shang
Klebsiella pneumoniae (Kp) can cause infections in communities and hospitals. After a report of a first highly virulent strain, it has now become the important pathogens that threatens human health and can often infect patients in intensive care units (ICUs). Kp is invasive and causes damage to the liver, pancreas, blood, intestines, and even the central nervous system. Zebrafish is a model organism with many advantages in biomedicine, and it has been used as a host to evaluate the virulence of Kp. However, there are no reports using zebrafish as a host to study the pathological characteristics of Kp. In this study, three Kp strains (KP1053, KP1196, and KP1195) were isolated from two clinical patients. The genetic and drug-susceptibility properties of the strains were first studied, and then zebrafish was used as a host to evaluate their virulence and pathogenicity. The three clinical Kp strains led to a marked decrease in the zebrafish survival rate, heart rate, and swimming distance; they also impeded the development of the swim bladder and resulted in a notable increase in the number of inflammatory cells. The virulence of these three strains followed the sequence KP1196 > KP1053 > KP1195. The transcriptome analysis found that lung, liver, nerve, and other developmental processes were significantly enriched in differentially expressed genes (DEGs), indicating that Kp may affect organ pathology through these genes. Our research offers a valuable reference for comprehending the pathological mechanisms underlying Kp clinical isolates.
肺炎克雷伯菌(Kp)可在社区和医院引起感染。在报告了第一个高毒力菌株之后,它现已成为威胁人类健康的重要病原体,并且经常可以感染重症监护病房(icu)的患者。Kp具有侵袭性,可对肝脏、胰腺、血液、肠道甚至中枢神经系统造成损害。斑马鱼是一种在生物医学上具有许多优势的模式生物,已被用作评价Kp毒力的宿主。然而,目前尚无以斑马鱼为宿主研究Kp病理特征的报道。本研究从2例临床患者中分离到3株Kp菌株(KP1053、KP1196和KP1195)。首先研究菌株的遗传和药敏特性,然后以斑马鱼为宿主对其毒力和致病性进行评价。3种临床Kp菌株导致斑马鱼存活率、心率和游泳距离显著降低;它们还阻碍了鱼鳔的发育,并导致炎症细胞数量的显著增加。这3株毒株的毒力序列为KP1196 >; KP1053 > KP1195。转录组分析发现,肺、肝、神经和其他发育过程中差异表达基因(DEGs)显著富集,表明Kp可能通过这些基因影响器官病理。我们的研究为理解Kp临床分离株的病理机制提供了有价值的参考。
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引用次数: 0
Genotype diversity and evolution of noroviruses GI.3[P13] associated acute gastroenteritis outbreaks in Beijing, China from 2016 to 2019 2016 - 2019年北京地区诺如病毒GI.3[P13]相关急性胃肠炎暴发的基因型多样性和进化
IF 2.6 4区 医学 Q3 INFECTIOUS DISEASES Pub Date : 2025-11-01 DOI: 10.1016/j.meegid.2025.105850
Lingyu Shen , Jiamei Fu , Baiwei Liu , Weihong Li , Yu Wang , Yi Tian , Lei Jia , Peng Yang , Quanyi Wang , Daitao Zhang , Jie Li , Gao Zhiyong

Objectives

This study aimed to characterize the epidemiological, clinical, and genomic features of norovirus GI.3[P13] outbreaks in Beijing from 2016 to 2019.

Methods

Stool specimens from acute gastroenteritis (AGE) outbreak cases were subjected to genotyping, whole-genome sequencing, and phylogenetic analysis.

Results

From 2016 to 2019, norovirus GI.3[P13] caused 29 AGE outbreaks (452 cases) in Beijing, becoming the second most prevalent strain, followed by GII.2[P16] in 2019. Phylogenetic analysis identified three subclades, with subclade 2.2 (213 cases, 19 outbreaks) demonstrating distinct epidemiological and clinical features. This emergent subclade exhibited year-round circulation in urban/suburban areas. Multivariate analysis identified male gender (aOR = 1.79), age ≥ 13 years (aOR = 9.12), and university (aOR = 6.82) as independent risk factors. As the clinical symptom, subclade 2.2 caused more severe symptoms, including higher frequencies of vomiting (≥7 episodes/day: 18.78 % vs ≤8.67 %), diarrhea (≥7 episodes/day: 35.2 % vs ≤16.7 %), and fever (50.70 % vs ≤18.70 %). Genomic analysis revealed mutations in key structural and non-structural proteins. Bayesian analysis estimated the divergence of subclade 2.2 around mid-2017 as potential novel subgenotypes, preceding its outbreak surge in 2019.

Conclusions

Norovirus GI genotypes, like GI.3[P13], circulate continuously as sporadic and can incite outbreak surges, highlighting the necessity for improved surveillance among these genotypes.
目的:研究2016 - 2019年北京市诺如病毒GI.3[P13]暴发的流行病学、临床和基因组特征。方法:对急性胃肠炎(AGE)暴发病例的粪便标本进行基因分型、全基因组测序和系统发育分析。结果:2016 - 2019年,诺如病毒GI.3[P13]在北京市共引起29起AGE暴发(452例),成为第二大流行毒株,2019年排在第二位的是gi .2[P16]。系统发育分析确定了3个亚支,其中亚支2.2(213例,19次暴发)表现出明显的流行病学和临床特征。这一新兴亚枝在城市/郊区全年循环。多变量分析发现男性性别(aOR = 1.79),年龄 ≥  13年(aOR = 9.12),和大学(aOR = 6.82)作为独立的危险因素。作为临床症状,亚枝2.2引起的症状更为严重,包括呕吐(≥7次/天:18.78 % vs≤8.67 %)、腹泻(≥7次/天:35.2% % vs≤16.7 %)和发烧(50.70 % vs≤18.70 %)的频率更高。基因组分析揭示了关键结构蛋白和非结构蛋白的突变。贝叶斯分析估计,在2019年爆发疫情之前,2017年年中左右2.2亚支的分化是潜在的新型亚基因型。结论:诺如病毒GI基因型与GI.3[P13]一样,以散发形式持续传播,并可引发疫情激增,因此有必要加强对这些基因型的监测。
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引用次数: 0
Chromosomal co-carriage of blaOXA-23 and blaOXA-500 in a carbapenem-resistant Acinetobacter pittii isolate 耐碳青霉烯不动杆菌pittii分离物中blaOXA-23和blaOXA-500的染色体共载。
IF 2.6 4区 医学 Q3 INFECTIOUS DISEASES Pub Date : 2025-11-01 DOI: 10.1016/j.meegid.2025.105845
Md Shohel Rana , Je Chul Lee , Shukho Kim
Carbapenem resistance in non-baumannii Acinetobacter has been increasingly reported worldwide. This study investigated the genetic basis of carbapenem resistance in Acinetobacter pittii isolate KBN12P06770 carrying blaOXA-23 and blaOXA-500 using whole-genome sequencing. Two carbapenemase genes were located on the chromosome. Two copies of blaOXA-23 located on Tn2006 were identified. Additional chromosomally encoded antimicrobial resistance genes, including blaADC-18 and ant(3“)-IIc, as well as efflux pump genes (adeIJK, adeFGH, abeM, and abaQ), were identified, with the exception of plasmid-borne ant(2”)-Ia. qPCR analysis revealed that the blaOXA-23 was more highly expressed than blaOXA-500. Notably, blaOXA-23 featured the Ser225Pro substitution, first characterized in this study, which may enhance β-lactamase activity based on structural modeling. Furthermore, multilocus sequence typing (MLST) assigned KBN12P06770 to ST1611 within clonal complex 63 (CC63), with close clustering to ST2737 indicating recent divergence. The comprehensive genomic analysis of A. pittii isolate KBN12P06770 highlights the complex genetic architecture underlying carbapenem resistance.
非鲍曼不动杆菌对碳青霉烯类耐药的报道越来越多。本研究利用全基因组测序技术研究了携带blaOXA-23和blaOXA-500的pittii不动杆菌分离株KBN12P06770对碳青霉烯类耐药的遗传基础。两个碳青霉烯酶基因位于染色体上。鉴定了位于Tn2006上的blaOXA-23的两个拷贝。除了质粒携带的蚂蚁(2”)-Ia外,还鉴定出了其他染色体编码的抗菌耐药基因,包括blaADC-18和ant(3”)-IIc,以及外排泵基因(adeIJK、adeFGH、abeM和abaQ)。qPCR分析显示,blaOXA-23的表达量高于blaOXA-500。值得注意的是,blaOXA-23具有Ser225Pro取代,这在本研究中首次被发现,根据结构建模,这可能会增强β-内酰胺酶的活性。此外,多位点序列分型(MLST)将KBN12P06770定位于克隆复合体63 (CC63)中的ST1611,与ST2737紧密聚类表明最近出现分化。pittii A. pittii分离物KBN12P06770的综合基因组分析突出了碳青霉烯抗性的复杂遗传结构。
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引用次数: 0
Complex evolutionary dynamics including reassortment drive genome diversity in human rotavirus species A circulating in Ireland 包括重组在内的复杂进化动力学驱动了爱尔兰流行的人类轮状病毒物种的基因组多样性。
IF 2.6 4区 医学 Q3 INFECTIOUS DISEASES Pub Date : 2025-11-01 DOI: 10.1016/j.meegid.2025.105848
Gabriel Gonzalez , Michael J. Carr , Helen Byrne , Aoife Colgan , Daniel Hare , Hirofumi Sawa , Cillian F. De Gascun , Jelle Matthijnssens , Zoe Yandle
Rotavirus A (RVA), belonging to the species Rotavirus alphagastroenteritidis, is among the most frequently diagnosed viral causes of gastroenteritis. The inclusion of RVA vaccines in the primary childhood immunisation schedules of multiple countries has led to significant reductions in yearly-reported cases. Nevertheless, such interventions may exert selective pressures that could result in the emergence of novel vaccine escape variants. RVA classification has traditionally focused on two of eleven gene segments encoding the capsid proteins, VP4 and VP7, which limits evolutionary assessments of genomic diversity and reassortments involving the other segments. A viral metagenomics approach (NetoVIR) was employed to investigate the genomic diversity of RVA in Ireland. The analysis focused on clinical samples (n = 140) collected from patients between 2015 and 2021. Besides the Wa-like or DS-1-like genotype constellations, 4/140 genomes (3 %) were identified as reassortant, with an NSP2 genotype 1 in a DS-1-like constellation. Also, we confirmed the circulation of OP354-like P[8] strains in six G9P[8] samples. Notably, these strains show dissimilarity in the antigenic epitopes of the VP4 protein compared to the Rotarix vaccine. Furthermore, we detected strains with an equine-like G3 (EQL-G3) VP7 gene within a DS-1-like constellation (n = 5/140, 4 %) and the unusual combination of G1P[8] with a DS-1-like constellation in 6/22 (27 %) of the G1P[8] samsples. Our study supports using a viral metagenomic approach for RVA genetic characterisation to determine pathogen diversity and reassortments. The public health implications of the identified reassortant RVA strains, requires investigations for any potential impacts on vaccine efficacies.
轮状病毒A (RVA)属于轮状病毒甲胃肠炎,是肠胃炎最常见的病毒性病因之一。许多国家将RVA疫苗纳入初级儿童免疫接种计划,导致每年报告的病例大幅减少。然而,这些干预措施可能会施加选择性压力,导致新的疫苗逃逸变体的出现。传统上,RVA分类主要集中在编码衣壳蛋白的11个基因片段中的两个,VP4和VP7,这限制了基因组多样性的进化评估和涉及其他片段的重组。采用病毒宏基因组学方法(NetoVIR)来研究爱尔兰RVA的基因组多样性。分析的重点是2015年至2021年间从患者中收集的临床样本(n = 140)。除了Wa-like或DS-1-like基因型星座外,4/140个基因组(3 %)被鉴定为重组,在DS-1-like星座中有一个NSP2基因型1。此外,我们还在6份G9P[8]样本中证实了op354样p[8]菌株的循环。值得注意的是,与Rotarix疫苗相比,这些菌株在VP4蛋白的抗原表位上表现出不同。此外,我们在ds -1样星座(n = 5/ 140,4 %)中检测到马G3 (EQL-G3) VP7基因,在G1P[8]样本的6/22(27 %)中检测到G1P[8]与ds -1样星座的罕见组合。我们的研究支持使用病毒宏基因组方法进行RVA遗传表征,以确定病原体的多样性和重组。已确定的重组RVA菌株的公共卫生影响需要调查对疫苗效力的任何潜在影响。
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引用次数: 0
Genomic insights into Erwinia amylovora prophages: Diversity, defense strategies, and phage-host coevolution 对淀粉状欧文菌噬菌体的基因组研究:多样性、防御策略和噬菌体-宿主共同进化。
IF 2.6 4区 医学 Q3 INFECTIOUS DISEASES Pub Date : 2025-10-31 DOI: 10.1016/j.meegid.2025.105846
Mohammadreza Rahimian , Bahman Panahi
Erwinia amylovora, the causative agent of fire blight in Rosaceae plants like apple and pear, is a major agricultural pathogen responsible for significant economic losses. This gram-negative phytopathogen has the potential to acquire antibiotic resistance and virulence genes, a situation that becomes more severe and restricts treatment options. Using an in silico approach, we analyzed 268 E. amylovora genomes and identified seven high-quality temperate prophages, all classified under Caudoviricetes, with average genome sizes of 44.2 kbp and 51 % GC content. These prophages exhibited unique genomic features, including tRNA genes (Ph-Ea644), anti-defense systems like ardc (Ph-Ea6–96), and regulatory/lysis genes (Ph-EaFC01). Comparative genomics and phylogenetic analyses grouped them into five clades, with Ph-Ea4–96, Ph-Ea3–97, and Ph-Ea2–97 being genetically identical. Functional annotation revealed streptomycin resistance genes and a CAZyme (GH23) in Ph-Ea7–3, virulence factors (e.g., alginate biosynthesis proteins), and six auxiliary metabolic genes (AMGs) linked to metabolic adaptation. Additionally, Ph-Ea644 encoded a cell wall-binding receptor protein. The prophages also carried defense systems (Gabija, CBASS) and 31 anti-CRISPR proteins (ACRs), suggesting evasion of host immunity. CRISPR-Cas analysis indicated fewer arrays and spacers in prophage-containing strains, underscoring CRISPR's role in lysogeny resistance. These findings highlight the genomic plasticity of E. amylovora prophages, their interactions with bacterial defenses, and their potential influence on pathogen evolution. This study enhances understanding of temperate phages in agricultural pathogens and underscores challenges in phage-based biocontrol strategies.
苹果、梨等蔷薇科植物的火疫病病菌是造成重大经济损失的主要农业病原菌。这种革兰氏阴性植物病原体有可能获得抗生素耐药性和毒力基因,这种情况变得更加严重,并限制了治疗选择。利用计算机方法分析了268个E. amylovora基因组,鉴定出7个高质量的温带前噬菌体,它们都属于Caudoviricetes,平均基因组大小为44.2 kbp, GC含量为51% %。这些噬菌体表现出独特的基因组特征,包括tRNA基因(Ph-Ea644)、抗防御系统如ardc (Ph-Ea6-96)和调节/裂解基因(Ph-EaFC01)。比较基因组学和系统发育分析将它们分为5个分支,其中Ph-Ea4-96、Ph-Ea3-97和Ph-Ea2-97在遗传上是相同的。功能注释揭示了Ph-Ea7-3中链霉素耐药基因和一个CAZyme (GH23)、毒力因子(如海藻酸盐生物合成蛋白)以及6个与代谢适应相关的辅助代谢基因(AMGs)。此外,Ph-Ea644编码细胞壁结合受体蛋白。这些噬菌体还携带防御系统(Gabija, CBASS)和31种抗crispr蛋白(ACRs),表明它们可以逃避宿主免疫。CRISPR- cas分析表明,在含有噬菌体的菌株中,较少的阵列和间隔物,强调了CRISPR在溶原性抗性中的作用。这些发现强调了E. amylovora噬菌体的基因组可塑性,它们与细菌防御的相互作用,以及它们对病原体进化的潜在影响。这项研究提高了对温带噬菌体在农业病原体中的认识,并强调了基于噬菌体的生物防治策略的挑战。
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引用次数: 0
Mutations in gyrA and gyrB among drug-resistant Mycobacterium tuberculosis isolates in South Korea 韩国耐药结核分枝杆菌分离株中gyrA和gyrB的突变
IF 2.6 4区 医学 Q3 INFECTIOUS DISEASES Pub Date : 2025-10-30 DOI: 10.1016/j.meegid.2025.105849
Seungmo Kim , Hwi-Jun Kim , Ryeun Heo , Hyeon-Su Kim , Jong-Myun Song , Cheon-Tae Kim , Hee-Jin Kim , Soul-hee Kim , Jeong-hui Gwon , Gicheon Bae , Sumi Kang , Kwang-Hyuk Seok , Eunseon Kim , Dae-Seon Han , Mi-So Kim , Hyeon-Ju Lee , Seonmi Shin , Arim Song , Gyeong In Lee , Seung-Heon Lee , Hee Joo Lee

Background

Group A fluoroquinolones (FLQs) are essential for treating multidrug-resistant tuberculosis (MDR-TB). Mutations in gyrA and gyrB cause FLQ resistance, but their patterns vary by region. This study evaluated FLQ-associated mutations in the gyrA and gyrB genes by analyzing minimum inhibitory concentrations (MICs) using 7H9 broth microdilution (BMD) and Löwenstein–Jensen phenotypic drug susceptibility test (L-J pDST).

Methods

A total of 304 isoniazid- and/or rifampicin-resistant isolates were analyzed. Genotypic drug susceptibility testing (gDST) was performed by sequencing gyrA (codons 74–113) and gyrB (codons 500–540). MICs for moxifloxacin (MFX) and levofloxacin (LFX) (0.0625–8.0 μg/mL) were determined using 7H9 BMD. Mutations were identified relative to the M. tuberculosis H37Rv reference. In L-J pDST, resistance breakpoints were 1.0 μg/mL for MFX and 2.0 μg/mL for LFX.

Results

Among isolates, 270 (88.81 %) were wild type and 34 (11.18 %) had mutations. D94G (44.82 %) and A90V (24.14 %) were the most frequent gyrA mutations. D500N (40 %) was the most common gyrB mutation. All gyrA mutants were MFX-resistant, while only 60 % of gyrB mutants were.

Conclusions

This study confirms gyrA mutations, especially D94G, as primary determinants of FLQ resistance in drug-resistant TB (including MDR-TB) in South Korea. gyrB mutations may also influence resistance. Combining gDST with phenotypic methods may improve resistance profiling.
背景:A类氟喹诺酮类药物(FLQs)是治疗耐多药结核病(MDR-TB)所必需的药物。gyrA和gyrB突变引起FLQ抗性,但其模式因地区而异。本研究利用7H9肉液微量稀释(BMD)和Löwenstein-Jensen表型药敏试验(L-J pDST)分析最低抑制浓度(mic),评估gyrA和gyrB基因中flq相关突变。方法:对304株异烟肼耐药和/或利福平耐药菌株进行分析。测序gyrA(密码子74 ~ 113)和gyrB(密码子500 ~ 540)进行基因型药敏试验(gDST)。采用7H9骨密度法测定莫西沙星(MFX)和左氧氟沙星(LFX)的mic(0.0625-8.0 μg/mL)。与结核分枝杆菌H37Rv参比鉴定出突变。在L-J pDST中,MFX的抗性断点为1.0 μg/mL, LFX的抗性断点为2.0 μg/mL。结果:野生型270株(88.81 %),突变株34株(11.18 %)。D94G(44.82 %)和A90V(24.14 %)是最常见的gyrA突变。D500N(40 %)是最常见的gyrB突变。所有的gyrA突变体都具有mfx抗性,而只有60% %的gyrB突变体具有mfx抗性。结论:本研究证实了gyrA突变——尤其是d94g——是韩国耐药结核病(包括耐多药结核病)中FLQ耐药的主要决定因素。gyrB突变也可能影响抗性。将gDST与表型方法结合可以改善抗性谱分析。
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引用次数: 0
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Infection Genetics and Evolution
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