Microbial pathogenesis最新文献_第9页

Diagnostic and pathological characterization of senecavirus A-associated epidemic transient neonatal losses in swine 猪赛尼卡病毒a相关的一过性新生儿死亡的诊断和病理特征

IF 3.5 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2026-01-13 DOI: 10.1016/j.micpath.2026.108303

Eduarda Ribeiro Braga, Emanoelly Machado Sousa da Silva, Anderson Hentz Gris, Jennifer Groeltz-Thrush, Pablo E. Piñeyro

Senecavirus A (SVA) has emerged as a significant viral pathogen of swine, traditionally associated with idiopathic vesicular disease but more recently linked to epidemic transient neonatal losses (ETNL), a syndrome characterized by increased mortality in piglets without consistent vesicular lesions. The mechanisms underlying SVA-associated neonatal mortality remain unclear due to the lack of specific clinical signs, frequent co-infections, and limited tissue characterization. This retrospective study analyzed 186 neonatal submissions (<24 days old) that were tested for SVA by RT-qPCR at the Iowa State University Veterinary Diagnostic Laboratory to elucidate the pathological, molecular, and microbial features associated with SVA infection. Clinical, histopathological, and microbiological data were compared between SVA-positive (n = 71) and SVA-negative (n = 253) cases, and selected tissues were analyzed by RNAscope® in situ hybridization (ISH) and immunohistochemistry (IHC) to localize viral RNA and assess co-infections with Rotavirus A and C. SVA was detected in 21.9 % of cases, most frequently in feces, serum, and spleen with significantly lower Ct values on spleen (p < 0.05), indicating a higher viral load and suggesting preferential replication in lymphoid tissues. RNAscope® analysis confirmed SVA RNA localization in spleen, lymph node, and within lymphoid aggregates of the lamina propria of the small intestine and colon, supporting a lymphoid tropism and possible immune cell replication. Clinically, diarrhea and increased mortality were the most frequent findings and were strongly associated with SVA detection (p < 0.001). The occurrence of co-infections was common; 28.2 % of SVA-positive animals had co-infection with Rotavirus A, while Rotavirus C and bacterial agents, such as Clostridium perfringens, E. coli, and Salmonella spp., were detected across both groups. Notably, respiratory pathogens including Streptococcus suis, Actinobacillus suis, and Streptococcus equisimilis were significantly more frequent in SVA-positive animals (p < 0.01), suggesting immunosuppression. Despite SVA's short viremic phase, its persistence in lymphoid tissues and association with mortality indicate a potential immunomodulatory role. These findings highlight SVA as a contributor to multifactorial neonatal disease, emphasizing the need for integrated molecular, histopathological, and epidemiological approaches to improve diagnosis and understanding of SVA pathogenesis.

塞内卡病毒A （SVA）已成为猪的一种重要的病毒性病原体，传统上与特发性水疱病有关，但最近与流行性短暂新生儿损失（ETNL）有关，这是一种以没有持续水疱病变的仔猪死亡率增加为特征的综合征。由于缺乏具体的临床症状、频繁的合并感染和有限的组织特征，sva相关新生儿死亡的机制尚不清楚。本回顾性研究在爱荷华州立大学兽医诊断实验室对186例新生儿（24日龄）进行了SVA RT-qPCR检测，以阐明与SVA感染相关的病理、分子和微生物特征。比较SVA阳性（71例）和SVA阴性（253例）患者的临床、组织病理学和微生物学资料，并采用RNAscope®原位杂交（ISH）和免疫组化（IHC）对所选组织进行定位病毒RNA和评估轮状病毒A和c的合并感染。SVA在21.9%的病例中检测到，最常发于粪便、血清和脾脏，脾脏Ct值显著低于对照组（p < 0.05）。表明更高的病毒载量，并暗示在淋巴组织中优先复制。RNAscope®分析证实SVA RNA定位于脾脏、淋巴结以及小肠和结肠固有层的淋巴样聚集体内，支持淋巴样趋向性和可能的免疫细胞复制。临床上，腹泻和死亡率增加是最常见的表现，并且与SVA检测密切相关（p < 0.001）。合并感染较为常见；28.2%的sva阳性动物同时感染了轮状病毒A，而轮状病毒C和细菌病原体，如产气荚膜梭菌、大肠杆菌和沙门氏菌，在两组中都被检测到。值得注意的是，呼吸道病原体包括猪链球菌、猪放线杆菌和同种链球菌在sva阳性动物中更常见（p < 0.01），提示免疫抑制。尽管SVA的病毒期很短，但它在淋巴组织中的持久性和与死亡率的相关性表明它具有潜在的免疫调节作用。这些发现强调SVA是多因素新生儿疾病的一个因素，强调需要综合分子、组织病理学和流行病学方法来提高SVA的诊断和理解发病机制。

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引用次数: 0

Differentially significant miRNA target gene analysis in exosomes extracted from Seneca Valley virus infected IBRS-2 cells 塞内卡谷病毒感染IBRS-2细胞外泌体中miRNA靶基因的差异分析

IF 3.5 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2026-01-13 DOI: 10.1016/j.micpath.2026.108300

Dajun Zhang , Guowei Xu , Wenxia Jiang , Dengshuai Zhao , Shikai Cai , Yuanhang Zhang , Ping Li , Han Gao , Fuqiang Huang , Shengfeng Chen , Feng Wen , LiMei Qin , Keshan Zhang

Exosomes are nanoscale extracellular vesicles secreted by a wide range of mammalian cells and serve as key mediators in the intercellular transfer of various biological materials such as proteins, nucleic acids, and lipids. However, it remains unclear whether microRNAs (miRNAs) present in exosomes derived from Seneca Valley virus (SVV)-infected IBRS-2 cells undergo substantial alterations. Moreover, the functions and regulatory pathways of differential miRNA target genes involved are unclear. In this study, Exosomes were isolated from SVV-infected IBRS-2 cells and examined for morphology, protein markers, and nucleic acid content using electron microscopy, western blotting, and PCR techniques. Then, the miRNAs present in the exosomes were sequenced, and Gene Ontology (GO) functional annotation along with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted on the target genes of differentially expressed miRNAs. Consequently, 1419 miRNAs were extracted from exosomes isolated from SVV-infected cells, and the GO functions of 281 differentially expressed miRNAs were related to RNA binding, nucleus, extracellular vesicular exosome, external side of the plasma membrane, cytoplasm, and nucleoplasm. In this study, we present the initial examination of the miRNA expression patterns and the functional roles of their related genes after SVV infects IBRS-2 cells. The results provide important information for investigating the pathogenesis of SVV and developing appropriate therapeutic strategies.

外泌体是由多种哺乳动物细胞分泌的纳米级细胞外囊泡，是多种生物材料（如蛋白质、核酸和脂质）细胞间转移的关键介质。然而，尚不清楚来自塞内卡谷病毒（SVV）感染的猪肾细胞（IBRS-2）的外泌体中存在的microRNAs （miRNAs）是否发生了实质性的改变。此外，涉及的差异miRNA靶基因的功能和调控途径尚不清楚。在这项研究中，从svv感染的IBRS-2细胞中分离出外泌体，并使用电子显微镜、western blotting和PCR技术检测形态学、蛋白质标记物和核酸含量。然后，对外泌体中存在的mirna进行测序，并对差异表达mirna的靶基因进行基因本体（GO）功能注释和京都基因与基因组百科全书（KEGG）途径富集分析。因此，从svv感染细胞分离的外泌体中提取了1419个mirna，其中280个差异表达mirna的氧化石墨烯功能与RNA结合、细胞核、细胞外泡外泌体、质膜外侧、细胞质和核质有关。在本研究中，我们初步检测了SVV感染IBRS-2细胞后miRNA的表达模式及其相关基因的功能作用。该结果为研究SVV的发病机制和制定适当的治疗策略提供了重要信息。

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引用次数: 0

Corrigendum to “The anti-biofilm potential of triterpenoids isolated from Sarcochlamys pulcherrima (Roxb.) Gaud (2019)” [Microb. Pathog. 139 (2020) 103901] “从石竹中分离的三萜的抗生物膜潜能”的勘误表。高德（2019）。中华病毒学杂志[j].中华病毒学杂志，2014,39(2020):103901。

IF 3.5 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2026-01-12 DOI: 10.1016/j.micpath.2026.108288

Chinmoy Ghosh , Joyanta Bhowmik , Ranjit Ghosh , Manash C. Das , Padmani Sandhu , Monika Kumari , Shukdeb Acharjee , Akshay Vishnu Daware , Yusuf Akhter , Birendranath Banerjee , Utpal Chandra De , Surajit Bhattacharjee

引用次数: 0

Orlistat impairs Chlamydia trachomatis development by disrupting its developmental cycle. 奥利司他通过破坏沙眼衣原体的发育周期而损害其发育。

IF 3.5 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2026-01-11 DOI: 10.1016/j.micpath.2026.108301

Jingpin Gao, Mingxin Jiang, Jianlin Chen, Hongbo Zhang

Chlamydia trachomatis is a common sexually transmitted bacterial pathogen that often causes urogenital infection and may progress to chronic inflammation and fibrosis due to its clinically silent nature. Although azithromycin and doxycycline are widely used for treatment, therapeutic failure has been documented in clinical cases. In this study, we demonstrate that orlistat disrupts the chlamydial developmental cycle both in vitro and in vivo. Orlistat inhibits early stages of chlamydial infection, reticulate body replication, and reticulate body-to-elementary body differentiation. Transcriptomic analysis revealed significant downregulation of multiple genes associated with mid-to-late developmental stages, indicating disruption of the chlamydial developmental program. These findings suggest that orlistat interferes with chlamydial growth and development, although the underlying mechanisms have not been fully defined.

沙眼衣原体是一种常见的性传播细菌病原体，常引起泌尿生殖系统感染，由于其临床沉默性，可发展为慢性炎症和纤维化。虽然阿奇霉素和强力霉素被广泛用于治疗，但在临床病例中有治疗失败的记录。在这项研究中，我们证明奥利司他在体外和体内都扰乱了衣原体的发育周期。奥利司他抑制衣原体感染、网状体复制和网状体向初级体分化的早期阶段。转录组学分析显示，与中后期发育阶段相关的多个基因显著下调，表明衣原体发育程序中断。这些发现表明奥利司他干扰衣原体的生长和发育，尽管潜在的机制尚未完全确定。

引用次数: 0

Marine Streptomyces-derived 2,4-di-tert-butylphenol enhances autophagy to eliminate mycobacteria in human macrophages 海洋链霉菌衍生的2,4-二叔丁基酚增强人巨噬细胞的自噬以消除分枝杆菌。

IF 3.5 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2026-01-10 DOI: 10.1016/j.micpath.2026.108297

Salina Patel , Shivananda Behera , Lincoln Naik , Mousumi Das , Dev Kiran Nayak , Pramathesh Kumar Dandsena , Mustafeez Ali Quaderi , Amit Mishra , Ramandeep Singh , Surajit Das , Rohan Dhiman

Mycobacterium tuberculosis (M. tb), the causative agent of tuberculosis (TB), remains a major global health threat, highlighting the need for novel therapeutic strategies. Host-directed therapies (HDTs), particularly autophagy induction via natural or pharmacological agents, offer promising strategies for combating mycobacteria. This study assessed the anti-mycobacterial potential of marine-derived Streptomyces spp. Briefly, the isolated marine Streptomyces spp. underwent primary and secondary screenings to assess their inhibitory activity against M. smegmatis. Notably, the cell-free extract of Streptomyces fradiae DNS4 (S. fradiae DNS4) demonstrated the most vigorous anti-mycobacterial activity. Optimization of culture conditions revealed maximal secondary metabolite production in ISP-7 medium at 28°C and pH 7 by S. fradiae DNS4. Furthermore, extraction using ethyl acetate, followed by GC-MS analysis, identified seventeen compounds, including the potent anti-mycobacterial secondary metabolite 2,4-di-tert-butylphenol [2,4-(DTBP)]. Subsequent experiments evaluated the host-directed anti-mycobacterial mechanism of action for 2,4-(DTBP) using dTHP-1 cells. At a non-cytotoxic concentration (10 μM), 2,4-(DTBP) treatment markedly reduced intracellular mycobacterial survival compared to untreated controls. Multiparametric investigations into autophagy induction, including LC3-I to LC3-II conversion, protein expression profiling of key autophagy markers, and MDC staining, demonstrated enhanced autophagic responses in 2,4-(DTBP)-treated macrophages. Upon 2,4-(DTBP) treatment, enhanced autophagic flux was further confirmed by increased LC3-II accumulation under Baf-A1 pre-treatment conditions. Importantly, autophagy inhibition by pre-treatment with 3-MA abolished the observed anti-mycobacterial effects, confirming the specific autophagy-dependent mechanism of 2,4-(DTBP). Collectively, these findings highlight the potential of marine-derived 2,4-(DTBP) from S. fradiae DNS4 as a novel host-directed anti-mycobacterial agent, which is mediated primarily through the targeted augmentation of autophagy in human macrophages.

结核病（tb）的病原体结核分枝杆菌（M. tb）仍然是一个主要的全球健康威胁，突出表明需要新的治疗策略。宿主定向治疗（HDTs），特别是通过天然或药物诱导自噬，为对抗分枝杆菌提供了有希望的策略。本研究评估了海洋链霉菌的抗分枝杆菌潜力。简单地说，对分离的海洋链霉菌进行了一次和二次筛选，以评估其对耻垢分枝杆菌的抑制活性。其中，传统链霉菌DNS4 （S. fradiae DNS4）无细胞提取物的抗分枝杆菌活性最强。优化培养条件发现，在28℃、pH为7的ISP-7培养基中，S. fradiae DNS4的次生代谢物产量最大。此外，采用乙酸乙酯提取，随后进行气相色谱-质谱分析，鉴定出17种化合物，包括有效的抗分枝杆菌次级代谢物2,4-二叔丁基苯酚[2,4-(DTBP)]。随后的实验利用dTHP-1细胞评估了宿主对2,4-(DTBP)的抗分枝杆菌作用机制。在非细胞毒性浓度（10 μM）下，与未治疗的对照组相比，2,4-(DTBP)治疗显著降低了细胞内分枝杆菌的存活率。自噬诱导的多参数研究，包括LC3-I到LC3-II的转化，关键自噬标志物的蛋白表达谱和MDC染色，表明2,4-(DTBP)处理的巨噬细胞的自噬反应增强。2,4-(DTBP)处理后，在Baf-A1预处理条件下，LC3-II积累增加，进一步证实了自噬通量的增强。重要的是，3-MA预处理的自噬抑制消除了观察到的抗分枝杆菌作用，证实了2,4-(DTBP)的特异性自噬依赖机制。总之，这些发现突出了S. fraae DNS4中海洋衍生的2,4-(DTBP)作为一种新型宿主定向抗分枝杆菌药物的潜力，其主要通过靶向增强人巨噬细胞的自噬来介导。

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引用次数: 0

Effect of antibody-dependent enhancement on the development of the offspring of mice infected by Zika virus: Analysis of the brain transcriptome 抗体依赖性增强对寨卡病毒感染小鼠后代发育的影响：脑转录组分析

IF 3.5 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2026-01-10 DOI: 10.1016/j.micpath.2026.108292

Letícia Maria Soares Azevedo , Diego Lisboa Rios , Larissa Nadur Arantes Diniz , Samantha Neves de Oliveira , Cínthia Firmo Teixeira , Danielle Cunha Teixeira , Vidyleison Neves Camargos , Antônio Lucio Teixeira , Frederico Soriani , Mauro Martins Teixeira , Vivian Vasconcelos Costa , Daniele G. Souza

Zika virus (ZIKV) is an arbovirus associated with neurological complications such as neonatal microcephaly and fetal anomalies, collectively referred to as congenital Zika syndrome. In the context of co-circulation with other arboviruses, it remains unclear whether pre-infection with a virus could be a risk factor for increased severity of ZIKV-induced disease. Here, we aimed to investigate whether there is differential gene expression in offspring of ZIKV-infected mothers pretreated with panflavivirus (4G2) at subneutralizing concentrations. Twelve weeks after birth, the offspring of these mothers were euthanized and their cerebral cortex was sampled for transcriptome analysis. Subsequently, the major differentially expressed genes (DEGs) were validated by RT-qPCR. Our results show that ZIKV infection induced fewer DEGs compared to the uninfected group, with the main findings being a suppression of genes related to cell cycle and morphogenesis. However, genes related to activation of the immune response and production of inflammatory mediators were preferentially expressed in the offspring of 4G2-treated mice compared to infected mice. Suppression of cellular and morphological processes was also observed, supporting ZIKV pathogenesis, particularly in the developing nervous system. The genetic and metabolic changes observed by transcriptomic analysis are therefore consistent with the more severe phenotypic observations in adult mice in previous studies. Our results contribute to the understanding of the severity of congenital ZIKV infection in the context of cross-reactivity of antibodies against other flaviviruses.

寨卡病毒是一种虫媒病毒，与新生儿小头畸形和胎儿异常等神经系统并发症相关，统称为先天性寨卡综合征。在与其他虫媒病毒共循环的情况下，尚不清楚病毒的预感染是否可能是zikv诱导疾病严重程度增加的一个危险因素。在这里，我们的目的是研究用亚中和浓度的泛黄病毒（4G2）预处理的感染zikv母亲的后代是否存在差异基因表达。出生12周后，这些母亲的后代被安乐死，他们的大脑皮层被取样进行转录组分析。随后，通过RT-qPCR验证主要差异表达基因（DEGs）。我们的研究结果表明，与未感染组相比，ZIKV感染诱导的deg较少，主要发现是与细胞周期和形态发生相关的基因受到抑制。然而，与感染小鼠相比，与免疫反应激活和炎症介质产生相关的基因在4g2处理小鼠的后代中优先表达。细胞和形态过程的抑制也被观察到，支持寨卡病毒的发病机制，特别是在发育中的神经系统。因此，转录组学分析观察到的遗传和代谢变化与先前研究中在成年小鼠中观察到的更严重的表型一致。我们的研究结果有助于了解先天性寨卡病毒感染的严重程度，在抗其他黄病毒的抗体交叉反应的背景下。

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引用次数: 0

Prim-O-glucosylcimifugin targets Staphylococcus aureus caseinolytic protease P to inhibit α-hemolysin expression and promote healing of MRSA-induced diabetic skin infections Prim-O-glucosylcimifugin靶向金黄色葡萄球菌溶酪蛋白蛋白酶P抑制α-溶血素表达，促进mrsa诱导的糖尿病皮肤感染愈合。

IF 3.5 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2026-01-09 DOI: 10.1016/j.micpath.2026.108296

Yan Wang, Shanshan Luo, Xinping Guo, Mengli Jin, Xingye Wang, Mingran Li, Shuang Jiang, Lin Wei, Mingjun Liu, Wu Song

Targeting bacterial virulence factors is considered a promising strategy because it poses a lower risk of promoting antibiotic resistance. This study investigated the therapeutic potential and underlying mechanism of prim-O-glucosylcimifugin (POG) against Staphylococcus aureus (S. aureus). In a diabetic mouse model, POG significantly reduced bacterial burden and accelerated wound healing, which was accompanied by enhanced tissue regeneration and collagen deposition, but no detectable toxicity. It also improved survival in a Galleria mellonella model infected with methicillin-resistant S. aureus. In vitro, POG did not inhibit bacterial growth, indicating an antivirulence rather than bactericidal mode of action. Transcriptomic analysis revealed that POG downregulated multiple virulence-associated genes, including α-hemolysin (hla), and disrupted quorum sensing, stress response, and metabolic pathways. Consistently, POG treatment suppressed hemolytic activity and the production of Hla. Molecular docking, molecular dynamics simulations, and cellular thermal shift assays confirmed the direct binding of POG to S. aureus caseinolytic protease P (SaClpP). Furthermore, fluorescence resonance energy transfer assays demonstrated that POG inhibited SaClpP activity in a dose-dependent manner, with an IC₅₀ of 14.27 μg/mL. In a clpP knockout strain, the suppressive effects of POG on Hla production and hemolytic activity were abolished, confirming SaClpP as the key target responsible for its antivirulence effects. Collectively, these results demonstrate that POG is a promising antivirulence agent that attenuates S. aureus pathogenicity by targeting SaClpP.

靶向细菌毒力因子被认为是一种很有前途的策略，因为它促进抗生素耐药性的风险较低。本研究探讨了prim-O-glucosylcimifugin （POG）对金黄色葡萄球菌（S. aureus）的治疗潜力及其作用机制。在糖尿病小鼠模型中，POG显著减少了细菌负担，加速了伤口愈合，并伴有组织再生和胶原沉积的增强，但没有检测到毒性。它还提高了感染耐甲氧西林金黄色葡萄球菌的大卖场菌模型的存活率。在体外，POG不抑制细菌生长，表明其具有抗毒作用而非杀菌作用。转录组学分析显示，POG下调了包括α-溶血素（hla）在内的多个毒力相关基因，并破坏了群体感应、应激反应和代谢途径。一致地，POG治疗抑制溶血活性和Hla的产生。分子对接、分子动力学模拟和细胞热移实验证实了POG与金黄色葡萄球菌溶酪蛋白蛋白酶P （SaClpP）的直接结合。荧光共振能量转移实验表明，POG抑制SaClpP活性呈剂量依赖性，IC50为14.27 μg/mL。在clpP敲除菌株中，POG对Hla产生和溶血活性的抑制作用被消除，证实SaClpP是其抗毒作用的关键靶点。综上所述，这些结果表明POG是一种很有前景的抗毒剂，可以通过靶向SaClpP来减弱金黄色葡萄球菌的致病性。

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引用次数: 0

YXL-13 attenuates virulence in Pseudomonas aeruginosa mutants and clinical isolates by inhibiting quorum sensing regulators LasR and RhlR YXL-13通过抑制群体感应调节因子LasR和RhlR降低铜绿假单胞菌突变体和临床分离株的毒力。

IF 3.5 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2026-01-09 DOI: 10.1016/j.micpath.2026.108298

Lei Wang , Rui Luo , Xinlin Yan , Mengliang Han , Mingjie Zhang , Junhai Xiao , Kelei Zhao , Feng Lin

Given the critical role of quorum sensing (QS) in the pathogenicity of Pseudomonas aeruginosa, inhibiting QS is considered a promising alternative to traditional antibiotics for treating P. aeruginosa infections. The QS system of P. aeruginosa comprises two acyl-homoserine lactone (AHL) circuits, LasI/R and RhlI/R, along with a third system, the PQS system. However, due to the frequent clinical isolation of lasR mutants and the avirulent nature of rhlR mutants, targeting both the LasI/R and RhlI/R systems represent a more viable therapeutic strategy. YXL-13, an AHL analog, has been identified as a QS inhibitor, though its precise molecular target remains unclear. This study demonstrates that YXL-13 effectively inhibits the QS response in P. aeruginosa QS mutants (ΔlasR, ΔrhlR, and ΔpqsR) as well as in clinically isolated strains (PA1, PA2, and PA3), while also providing protection to C. elegans against infection. The related evidences, including qPCR analysis, QS reporter assays, isothermal titration calorimetry (ITC), molecular docking, and molecular dynamics (MD) simulations, indicate that YXL-13 targets both LasR and RhlR. In summary, YXL-13 exhibits potent inhibitory effects on the QS response of various P. aeruginosa strains.

鉴于群体感应（QS）在铜绿假单胞菌致病性中的关键作用，抑制QS被认为是治疗铜绿假单胞菌感染的一种有希望的替代传统抗生素。P. aeruginosa的QS系统包括LasI/R和RhlI/R两个酰基同丝氨酸内酯（AHL）回路，以及第三个系统PQS系统。然而，由于lasR突变体的频繁临床分离和rhlR突变体的无毒性，靶向LasI/R和RhlI/R系统代表了一种更可行的治疗策略。YXL-13是一种AHL类似物，已被确定为QS抑制剂，但其精确的分子靶标尚不清楚。本研究表明，YXL-13能有效抑制铜绿假单胞菌QS突变体（ΔlasR、ΔrhlR和ΔpqsR）以及临床分离菌株（PA1、PA2和PA3）的QS反应，同时还能保护秀丽隐杆线虫免受感染。包括qPCR分析、QS报告基因分析、等温滴定量热法（ITC）、分子对接和分子动力学（MD）模拟在内的相关证据表明，YXL-13同时靶向LasR和rhr。综上所述，YXL-13对不同铜绿假单胞菌的QS反应具有较强的抑制作用。

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引用次数: 0

Characterization of a Salmonella strain isolated from Tibetan blue sheep 一株西藏蓝羊沙门氏菌的分离鉴定。

IF 3.5 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2026-01-09 DOI: 10.1016/j.micpath.2026.108276

Huaguo Huang, Xin Guan, Tiannan Zhao, Mimi Zhang

Considering the ecological importance of blue sheep and the lack of information regarding their infection status, this study aimed to determine the causes of diarrhea and death in blue sheep in the Shigatse region. A key strain that caused diarrhea and even death in blue sheep was isolated from fecal samples and analyzed using morphological observation, biochemical tests, 16S rRNA genetic analysis, mouse pathogenicity tests, and drug susceptibility tests. The strains were grouped into pairs, short chains, or Gram-negative bacilli. The biochemical results were consistent with those obtained for Salmonella spp. The 16S rRNA sequence shared 100 % homology with Salmonella sequences in the NCBI database. The results indicated that the isolated strain was Salmonella, which was named G1GX051. G1GX051 showed strong pathogenicity upon intraperitoneal injection of 1.0 × 10⁴, 1.0 × 10⁶, 1.0 × 10⁸ CFU/mL bacterial solutions (0.2 mL) to SPF grade mice (six per group). Notably, the entre group inoculated with 1.0 × 10⁸ CFU/mL died within 6 days of injection. Anatomical analysis revealed necrotic foci on the liver surface, spleen swelling, a dark red and distended stomach, intestinal congestion, thinning of the intestinal wall, and a firm and congested ileocecal valve. Histopathological analyses revealed spleen and kidney congestion, as well as inflammatory cell infiltration. Drug sensitivity analysis indicated that G1GX051 was resistant only to erythromycin. Overall, G1GX051 isolated from blue sheep with diarrhea was resistant to erythromycin but responsive to several other medicines, indicating the need for monitoring bacterial resistance in wildlife.

考虑到蓝羊在生态上的重要性和其感染状况的信息缺乏，本研究旨在确定日喀则地区蓝羊腹泻和死亡的原因。从蓝羊粪便中分离出一株导致蓝羊腹泻甚至死亡的关键菌株，通过形态学观察、生化试验、16S rRNA遗传分析、小鼠致病性试验和药敏试验对其进行分析。菌株分为成对、短链和革兰氏阴性杆菌。生化结果与沙门氏菌一致，16S rRNA序列与NCBI数据库中沙门氏菌序列同源性为100%。结果表明，分离得到的菌株为沙门氏菌，命名为G1GX051。SPF级小鼠（每组6只）腹腔注射1.0 × 104、1.0 × 106、1.0 × 108 CFU/mL菌液（0.2 mL）， G1GX051表现出较强的致病性。值得注意的是，接种1.0 × 108 CFU/mL的对照组在注射后6天内死亡。解剖分析显示肝表面坏死灶，脾脏肿胀，胃深红色膨胀，肠充血，肠壁变薄，回盲瓣坚硬充血。组织病理学分析显示脾、肾充血，炎症细胞浸润。药敏分析显示，G1GX051仅对红霉素耐药。总体而言，从腹泻蓝羊中分离出的G1GX051对红霉素有耐药性，但对其他几种药物有反应，这表明有必要监测野生动物的细菌耐药性。

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引用次数: 0

Hepatitis B virus induces T cell exhaustion by increasing mitochondrial ROS accumulation 乙型肝炎病毒通过增加线粒体ROS积累诱导T细胞衰竭。

IF 3.5 3区医学 Q3 IMMUNOLOGY

Microbial pathogenesis

Pub Date : 2026-01-09 DOI: 10.1016/j.micpath.2026.108289

Longji Cheng , Rui Qiang , Huafeng Song , Qinhao Zhou , Xing Lv , Minjuan Wu , Junchi Xu , Ping Xu

This study seeks to examine the fluctuating levels of mitochondrial reactive oxygen species (ROS) in peripheral blood T cells of individuals with chronic hepatitis B (CHB) and their immunological implications. The study encompassed 95 participants, consisting of 23 healthy volunteers and 72 HBV-infected individuals positive for HBsAg. The study conducted a prospective analysis of HBV-DNA levels in the peripheral blood of patients. Flow cytometry was utilized to evaluate mitochondrial ROS levels and programmed death receptor-1 (PD-1) expression in T cells. Enzyme-linked immunosorbent assay (ELISA) was utilized to quantify γ-interferon (IFN-γ) levels in the plasma of individuals infected with HBV.The study revealed a positive correlation between ROS levels generated by CD8⁺ and CD4⁺ T cells and serum HBV-DNA load (p < 0.05). In comparison to the healthy control group (HC), CHB patients exhibited a notable increase in the proportion of CD8⁺ and CD4⁺ T cells expressing the exhaustion marker PD-1 in peripheral blood (p < 0.05). Furthermore, ROS levels produced by T cell subpopulations expressing PD-1 were significantly elevated compared to those not expressing PD-1 (p < 0.05). Additionally, plasma levels of IFN-γ were significantly inversely associated with serum HBV-DNA load and ROS production by CD8⁺ T cells (p < 0.05).These findings indicate that an elevated viral load in individuals with CHB is closely linked to the accumulation of mitochondrial ROS in T cells. We observed that this ROS accumulation is concurrent with increased PD-1 expression and reduced IFN-γ production. Therefore, we hypothesize that mitochondrial dysfunction may be a key factor driving T cell exhaustion in this setting.

本研究旨在研究慢性乙型肝炎（CHB）患者外周血T细胞中线粒体活性氧（ROS）水平的波动及其免疫学意义。该研究包括95名参与者，包括23名健康志愿者和72名HBsAg阳性的hbv感染者。该研究对患者外周血中HBV-DNA水平进行了前瞻性分析。流式细胞术检测T细胞线粒体ROS水平和程序性死亡受体-1 （PD-1）表达。采用酶联免疫吸附试验（ELISA）定量HBV感染者血浆中γ-干扰素（IFN-γ）水平。研究发现，CD8+和CD4+ T细胞产生的ROS水平与血清HBV-DNA负荷（p+）和外周血表达衰竭标志物PD-1的CD4+ T细胞（p+ T细胞）呈正相关

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