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The role of neuraminidase NanH in drug-induced phagocytic resistance of G. parasuis and its targeted intervention 神经氨酸酶NanH在副猪螺旋体药物性吞噬耐药中的作用及其靶向干预。
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2026-01-30 DOI: 10.1016/j.vetmic.2026.110905
Yuqing Tan , Ze Li , Shijiao Huan , Yaqin Liu , Hengming Liu , Shenglan Liu , Zhixin Lei

Background

Glaesserella parasuis (G. parasuis) is the core pathogen of porcine respiratory disease syndrome (PRDC), and the co-evolution of its drug resistance and virulence has seriously threatened the biosecurity of the global pig farming industry.

Objective

This study aims to clarify the core function of neuraminidase (NanH) in the formation and pathogenic mechanism of G. parasuis resistance and explore its feasibility as a novel therapeutic target.

Method

Drug-resistant strains were induced by tildipirosin combined with florfenicol (MIC increased to 16 μg/mL), and the mechanism of drug resistance was systematically analyzed by transcriptomics, gene knockout and multi-model infection experiments.

Result

The activity of the ABC transport system in drug-resistant strains was enhanced, the virulence genes VapC and artM were upregulated, the smoothness of the cell wall increased, and host autophagy was significantly inhibited (LC3-II transformation decreased, P < 0.01). The nanH gene was highly expressed in drug-resistant strains. Its deletion (ΔnanH) reduced bacterial adhesion by 57 % (P < 0.01), decreased mouse mortality by 70 % (P < 0.005), and inhibited the transcription of COX-2 and TNF-α. The autophagy-targeted chimeric (NanH-AUTAC) designed based on the targeted protein degradation (TPD) strategy achieved a degradation rate of 60 % for NanH-EGFP at 40 μM.

Conclusion

NanH is a key regulatory factor in the co-evolution of G. parasuis drug resistance and virulence, and can serve as a potential target for anti-infection treatment. The "disarming" strategy based on TPD provides a new direction for dealing with drug-resistant bacterial infections.
背景:副猪Glaesserella parasuis (G. parasuis)是猪呼吸系统疾病综合征(PRDC)的核心病原体,其耐药性和毒力的共同进化严重威胁着全球养猪业的生物安全。目的:阐明神经氨酸酶(NanH)在副猪螺旋体耐药形成中的核心作用及其致病机制,探讨其作为新型治疗靶点的可行性。方法:采用替地匹罗辛联合氟苯尼考诱导耐药菌株(MIC升高至16 μg/mL),通过转录组学、基因敲除和多模型感染实验系统分析耐药机制。结果:耐药菌株ABC转运系统活性增强,毒力基因VapC和artM表达上调,细胞壁平滑度增加,宿主自噬明显受到抑制(LC3-II转化减少,P 结论:NanH是副猪螺旋体耐药和毒力协同进化的关键调控因子,可作为抗感染治疗的潜在靶点。基于TPD的“解除武装”策略为处理耐药细菌感染提供了新的方向。
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引用次数: 0
Distinct mechanisms of ER stress-mediated autophagy induction by high- and low-virulence pseudorabies virus strains 高毒力和低毒力伪狂犬病毒株内质网应激诱导自噬的不同机制
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2026-01-30 DOI: 10.1016/j.vetmic.2026.110914
Yueqing Lv , Xiangmei Huang , Zhipei Lu , Xiaoying Feng , Kang Ouyang , Ying Chen , Zuzhang Wei , Weijian Huang , Yifeng Qin
Pseudorabies virus (PRV) is one of the most significant pathogens threatening the swine industry, and its infection has caused substantial economic losses to pig farming worldwide. This study utilized two PRV strains isolated by our laboratory: the GXLB-2015 strain, a natural recombinant between a PRV variant strain and the Bartha-K61 vaccine strain, which exhibits stronger virulence, and the GXGG-2016 strain, a classical genotype II PRV strain with a natural 69-amino acid deletion in its TK gene, which demonstrates weak virulence and is non-pathogenic in mice. Focusing on endoplasmic reticulum stress (ERS) and cellular autophagy, this research explored the molecular mechanisms underlying the significant difference in virulence between these two PRV strains. The results revealed that infection with both strains induced noticeable ERS and autophagy, both of which inhibited viral replication. Further investigation showed that upon ERS induction, the GXLB-2015 strain mediated autophagy by activating both the PERK-eIF2α-ATF4-CHOP and IRE1-XBP1 pathways; inhibiting these pathways suppressed viral replication. In contrast, the GXGG-2016 strain infection mediated autophagy primarily through activating only the IRE1-XBP1 pathway, and inhibiting this pathway had no significant impact on viral replication. These findings indicate that while PRV infection can induce cellular autophagy by activating ERS, the specific unfolded protein response (UPR) pathways involved differ significantly between strains of varying virulence. This study provides a foundation for understanding the pathogenesis of different PRV strains and developing novel antiviral drugs.
伪狂犬病毒(PRV)是威胁养猪业最重要的病原体之一,其感染给世界范围内的养猪业造成了巨大的经济损失。本研究采用本实验室分离的两株PRV: GXLB-2015株是PRV变异株与Bartha-K61疫苗株之间的天然重组株,具有较强的毒力;GXGG-2016株是典型的基因II型PRV株,其TK基因天然缺失69个氨基酸,毒力弱,对小鼠无致病性。本研究以内质网应激(endoplasmic reticulum stress, ERS)和细胞自噬为研究重点,探讨了两种PRV毒株毒力显著差异的分子机制。结果表明,这两种菌株的感染均诱导了明显的ERS和自噬,两者均抑制了病毒复制。进一步研究发现,在ERS诱导下,GXLB-2015菌株通过激活PERK-eIF2α-ATF4-CHOP和IRE1-XBP1通路介导自噬;抑制这些途径可抑制病毒复制。相比之下,GXGG-2016菌株感染主要通过激活IRE1-XBP1途径介导自噬,抑制该途径对病毒复制无显著影响。这些发现表明,虽然PRV感染可以通过激活ERS诱导细胞自噬,但所涉及的特异性未折叠蛋白反应(UPR)途径在不同毒力的菌株之间存在显著差异。该研究为了解不同PRV毒株的发病机制和开发新型抗病毒药物提供了基础。
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引用次数: 0
Prevalence and diversity of non-tuberculous mycobacteria isolated from slaughtered tuberculin-positive bovine samples: Epidemiological and Diagnostic implications 从屠宰结核菌阳性牛样本中分离出的非结核分枝杆菌的患病率和多样性:流行病学和诊断意义
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2026-01-29 DOI: 10.1016/j.vetmic.2026.110909
Natalia Jiménez-Pizarro , David Risco , Felipe Molina , Remigio Martínez , Alfredo García , José Manuel Benítez-Medina , Javier Hermoso-de-Mendoza
The isolation of non-tuberculous mycobacteria (NTM) is common in cattle positive for tuberculosis (TB) in official diagnostic tests, whereas data on specific NTM species in Spanish cattle remain limited. This study identifies the most frequently isolated NTM species from Single Intradermal Tuberculin Test (SITT)-positive cattle in Extremadura, western Spain. Among 1669 Mycobacterium Growth Indicator Tube (MGIT) positive cultures collected in 2018, 493 (29.54 %) were identified as NTM, and 194 were randomly selected for further analysis. Polymerase Chain Reaction (PCR)-restriction analysis of the hsp65 gene and partial sequencing of 16S ribosomal DNA (rDNA) confirmed a diverse range of species. The most prevalent complex was Mycobacterium avium (40.12 %), including M. senriense, M. intracellulare, and M. avium subsp. paratuberculosis. Other notable NTM species (23.35 %) included M. bourgelatii, M. kansasii, M. gordonae, and M. shinjukuense. Less frequent complexes included M. simiae (11.38 %), M. ulcerans (3.59 %), M. parafortuitum (2.99 %), and M. terrae (1.20 %), along with M. holsaticum (1.20 %), a species related to the M. tuberculosis complex. Phylogenetic analysis and geographic mapping revealed weak correlation between genetic and geographic distances (Mantel test: Rxy = 0.015, P = 0.253), suggesting limited spatial structuration of genetic diversity. Alpha diversity metrics indicated moderate diversity (Shannon’s H = 2.641, Simpson’s D = 0.106), with some zones exhibiting greater species evenness. Diversity analyses showed moderate dissimilarity among clusters. These findings enhance understanding of Mycobacterium diversity and distribution while emphasizing the diagnostic challenges posed by NTM in TB detection and the importance of molecular tools in species identification and epidemiological surveillance.
非结核分枝杆菌(NTM)的分离在官方诊断测试中结核病(TB)阳性的牛中很常见,而西班牙牛中特定NTM物种的数据仍然有限。本研究确定了西班牙西部埃斯特雷马杜拉单一皮内结核菌素试验(SITT)阳性牛中最常分离的NTM物种。在2018年收集的1669株分枝杆菌生长指示管(MGIT)阳性培养物中,鉴定为NTM的有493株(29.54 %),随机抽取194株进行进一步分析。聚合酶链反应(PCR)- hsp65基因的限制性分析和16S核糖体DNA (rDNA)的部分测序证实了物种的多样性。最常见的复体是鸟分枝杆菌(40.12 %),包括senriense分枝杆菌、胞内分枝杆菌和鸟分枝杆菌亚种。副结核。其他显著的NTM种包括布氏支原体、甘肃支原体、戈登支原体和新injukuense支原体(23.35 %)。较不常见的复合体包括相似分枝杆菌(11.38 %)、溃疡分枝杆菌(3.59 %)、副fortuitum分枝杆菌(2.99 %)和地分枝杆菌(1.20 %),以及与结核分枝杆菌复合体相关的holsatium分枝杆菌(1.20 %)。系统发育分析和地理图谱显示,遗传多样性与地理距离的相关性较弱(Mantel检验:Rxy = 0.015, P = 0.253),表明遗传多样性的空间结构有限。α多样性指标表现为中等水平(Shannon’s H = 2.641, Simpson’s D = 0.106),部分地区物种均匀度较高。多样性分析显示集群间存在适度差异。这些发现加强了对分枝杆菌多样性和分布的认识,同时强调了结核分枝杆菌在结核病检测中的诊断挑战以及分子工具在物种鉴定和流行病学监测中的重要性。
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引用次数: 0
Whole-genome analysis of Ornithobacterium rhinotracheale from turkeys in Poland: Insights into global diversity, virulence, and antimicrobial resistance 波兰火鸡鼻气管鸟杆菌的全基因组分析:对全球多样性、毒力和抗菌素耐药性的见解。
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2026-01-27 DOI: 10.1016/j.vetmic.2026.110908
Marek Blanda , Olimpia Kursa , Joanna Kowalczyk , Marcin Śmiałek
Ornithobacterium rhinotracheale (ORT) is an emerging avian respiratory pathogen of global concern, causing significant economic losses, particularly in turkeys. Although its distribution is worldwide, genomic data from different geographic regions remain scarce, limiting understanding of its genetic diversity, virulence-associated features, and antimicrobial resistance profiles. In this study, we performed whole-genome sequencing of 49 O. rhinotracheale isolates recovered from respiratory tract and joint lesions during outbreaks of ornithobacteriosis in turkeys in Poland to characterize sequence types and explore the genomic diversity and the distribution of virulence- and resistance-associated genes. Comparative multilocus sequence typing revealed high genetic heterogeneity, including three novel sequence types (ST46, ST50, ST51), highlighting ongoing local diversification within a globally distributed pathogen. Whole-genome core single nucleotide polymorphism (SNP)–based phylogenetic analysis further resolved genetic relationships among isolates and identified major genomic clusters. Genomic profiling identified several virulence-associated genes and insertion sequences, including IS4351 and ISMlu9. Distinct resistance gene patterns observed between major STs (ST3, ST46) were observed. These findings provide new insights into the genomic diversity of O. rhinotracheale populations and contribute to a broader understanding of its epidemiology and antimicrobial resistance in poultry worldwide.
鼻气管鸟杆菌(ORT)是一种新兴的全球关注的禽类呼吸道病原体,造成重大的经济损失,特别是在火鸡中。尽管其分布在世界各地,但来自不同地理区域的基因组数据仍然稀缺,限制了对其遗传多样性、毒力相关特征和抗微生物药物耐药性谱的了解。在这项研究中,我们对波兰火鸡鸟杆菌病暴发期间从呼吸道和关节病变中分离出来的49株O. rhinotracheale进行了全基因组测序,以表征序列类型,并探索基因组多样性以及毒力和耐药性相关基因的分布。比较多位点序列分型显示了高度的遗传异质性,包括三种新的序列类型(ST46, ST50, ST51),突出了在全球分布的病原体中正在进行的局部多样化。基于全基因组核心单核苷酸多态性(SNP)的系统发育分析进一步确定了分离株之间的遗传关系,并确定了主要的基因组簇。基因组分析鉴定了几个毒力相关基因和插入序列,包括IS4351和ISMlu9。主要STs (ST3, ST46)之间存在不同的抗性基因模式。这些发现为O. rhinotracheale种群的基因组多样性提供了新的见解,并有助于更广泛地了解其在全球家禽中的流行病学和抗菌素耐药性。
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引用次数: 0
Intestinal organoids screening reveals: 3BDO as an inhibitor of porcine coronaviruses entry by targeting IFITM3. 肠道类器官筛选显示:3BDO可通过靶向IFITM3抑制猪冠状病毒的进入。
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2026-01-27 DOI: 10.1016/j.vetmic.2026.110907
Yunhang Zhang, Tianmeng Shi, Kuan Zhao, Wuchao Zhang, Baishi Lei, Guangliang Liu, Wanzhe Yuan

Porcine coronaviruses pose a major threat to the global pig industry, causing severe disease and high mortality in piglets. Despite the implementation of various control measures, these viruses continue to hinder the sustainable development of pig farming. To better control the prevalence of porcine coronaviruses, we utilized intestinal organoids as a drug-screening platform to identify effective and safe antiviral agents. The results showed that 3BDO significantly inhibits transmissible gastroenteritis virus (TGEV) infection in intestinal organoid monolayers, with a 50 % inhibitory concentration (IC₅₀) of 14.6 µM and a high selectivity index (SI = 87.67). Further analyses suggested that 3BDO inhibits TGEV internalization, which is associated with its ability to enhance the protein abundance of interferon-induced transmembrane protein 3 (IFITM3), a well-known inhibitor of virus-cell membrane fusion. Consistently, knockdown of IFITM3 abolished the antiviral activity of 3BDO. Moreover, 3BDO also inhibited porcine epidemic diarrhea virus (PEDV) and porcine respiratory coronavirus (PRCV) entry through the same mechanism. Overall, this study identifies 3BDO as a promising antiviral candidate for the prevention and control of porcine coronaviruses infections.

猪冠状病毒对全球养猪业构成重大威胁,造成仔猪严重疾病和高死亡率。尽管实施了各种控制措施,但这些病毒继续阻碍养猪业的可持续发展。为了更好地控制猪冠状病毒的流行,我们利用肠道类器官作为药物筛选平台,筛选有效安全的抗病毒药物。结果表明,3BDO显著抑制肠道类器官单层中传染性胃肠炎病毒(TGEV)的感染,其50 %的抑制浓度(IC₅₀)为14.6 µM,选择性指数高(SI = 87.67)。进一步分析表明,3BDO抑制TGEV内化,这与其增强干扰素诱导的跨膜蛋白3 (IFITM3)蛋白丰度的能力有关,IFITM3是一种众所周知的病毒-细胞膜融合抑制剂。同样,IFITM3的敲低会破坏3BDO的抗病毒活性。此外,3BDO还通过相同的机制抑制猪流行性腹泻病毒(PEDV)和猪呼吸道冠状病毒(PRCV)的进入。总体而言,本研究确定3BDO是预防和控制猪冠状病毒感染的有前途的抗病毒候选药物。
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引用次数: 0
Faecalibacterium prausnitzii derived postbiotic attenuates PEDV-induced mitochondrial apoptosis through blocking viral entry prausnitzii粪杆菌衍生的生物后通过阻断病毒进入来减弱pedv诱导的线粒体凋亡
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2026-01-27 DOI: 10.1016/j.vetmic.2026.110880
Lingcong Deng , Rui Luo , Shihan Yang , Letian Li , Nan Li , Yu Dong , Jiayi Hao , Ju Li , Anqi Deng , Xueyan Ai , Maopeng Wang , Chang Li
Porcine epidemic diarrhea virus (PEDV) damaged to the intestinal epithelial cells of suckling piglets, resulting in elevated mortality rates and substantial economic losses. This study aimed to evaluate the effect of F. prausnitzii on PEDV invasion and mitochondrial function in cells. Our study demonstrated that F. prausnitzii exhibited strongly adhesion to PEDV virions, thereby preventing their entry into cells and enhancing cell viability. Notably, F. prausnitzii inhibited PEDV-induced apoptosis in Vero-E6 cells, as indicated by decreased activation of PARP, caspase-3/9, and the Bax/Bcl-2 ratio, while preserving mitochondrial structure and membrane potential. Moreover, the adhesion-mediated inhibition of the PEDV-induced mitochondrial apoptotic pathway was correlated with reduced reactive oxygen species (ROS) production and cytochrome c translocation. These results suggested that F. prausnitzii as postbiotic may serve as a preventive measures against different subtype PEDV infection by targeting mitochondrial apoptotic pathways, and broadened the horizons for the antiviral effects of postbiotic.
猪流行性腹泻病毒(PEDV)破坏了哺乳仔猪的肠上皮细胞,导致死亡率升高和巨大的经济损失。本研究旨在探讨F. prausnitzii对PEDV侵袭及线粒体功能的影响。我们的研究表明,F. prausnitzii对PEDV病毒粒子表现出强烈的粘附性,从而阻止它们进入细胞,提高细胞活力。值得注意的是,F. prausnitzii抑制pedvv诱导的Vero-E6细胞凋亡,通过降低PARP、caspase-3/9和Bax/Bcl-2比值的激活,同时保持线粒体结构和膜电位。此外,粘附介导的pedv诱导的线粒体凋亡途径的抑制与活性氧(ROS)产生减少和细胞色素c易位相关。这些结果表明,prausnitzii作为后生物可能通过靶向线粒体凋亡途径预防不同亚型PEDV感染,拓宽了后生物抗病毒作用的研究视野。
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引用次数: 0
Salt inactivation kinetics of six porcine viruses in a 3D collagen model, simulating natural sausage casings 模拟天然香肠肠衣的三维胶原蛋白模型中六种猪病毒的盐失活动力学
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2026-01-26 DOI: 10.1016/j.vetmic.2026.110902
Tinka Jelsma , Joris J. Wijnker , Eline Verheij , Wim H.M. van der Poel , Henk J. Wisselink
Natural sausage casings are derived from intestines of regularly slaughtered pigs, bovines and small ruminants. Although casings are derived only from healthy animals after mandatory veterinary inspection, some slaughtered animals may originate from areas where contagious animal viral diseases are endemic. A validated 3D collagen model was used to establish inactivation kinetics of bovine viral diarrhoea virus (BVDV), porcine epidemic diarrhoea virus (PEDV), porcine reproductive and respiratory syndrome virus (PRRSV), pseudorabies virus (PrV), swine vesicular disease virus (SVDV) and transmissible gastroenteritis virus (TGEV) following treatment with saturated sodium chloride (NaCl) brine in line with the common production process of natural casings and alternatively a phosphate supplemented sodium chloride (P-salt). Decimal reduction values (D-values), representing time needed to reduce the initial viral load by 1 log10 (or 90 %), were determined at 4°C, 12°C and 20°C. For PRRSV and PrV, NaCl treatment at 12°C and 20°C was effective in lowering D-values significantly, while opposite results were found for BVDV, PEDV, SVDV and TGEV. Compared to the non-treatment, P-salt significantly decreased D-values for each virus at all temperatures, except for PrV and SVDV at 4°C. Despite clear thermal inactivation, no consistent correlation was found between salt inactivation and virus characteristics, like enveloped versus non-enveloped, DNA versus RNA viruses, and virion sizes. However, for individual viruses, the presented D-values can be used for future quantitative microbial risk assessment (QMRA) and to support emergency protocols and precautionary measures for sourcing of natural casings in cases of an acute outbreak of viral disease in endemic areas.
天然香肠肠衣取自定期屠宰的猪、牛和小型反刍动物的肠道。虽然肠衣只来自经过强制性兽医检查的健康动物,但一些屠宰的动物可能来自流行传染性动物病毒疾病的地区。采用三维胶原蛋白模型建立牛病毒性腹泻病毒(BVDV)、猪流行性腹泻病毒(PEDV)、猪繁殖与呼吸综合征病毒(PRRSV)、伪狂犬病毒(PrV)、猪流行性腹泻病毒(BVDV)、猪流行性腹泻病毒(PEDV)的灭活动力学。猪水疱病病毒(SVDV)和传染性肠胃炎病毒(TGEV)在用符合天然肠肠液常规生产工艺的饱和氯化钠(NaCl)盐水处理后,或者用磷酸盐补充氯化钠(p -盐)处理。在4°C, 12°C和20°C下测定十进制还原值(d值),表示将初始病毒载量降低1 log10(或90%)所需的时间。对于PRRSV和PrV, 12°C和20°C NaCl处理能显著降低d值,而对于BVDV、PEDV、SVDV和TGEV则相反。与未处理相比,p盐在所有温度下都显著降低了每种病毒的d值,但在4°C时,PrV和SVDV除外。尽管存在明显的热失活,但盐失活与病毒特性(如包膜病毒与非包膜病毒、DNA病毒与RNA病毒以及病毒粒子大小)之间没有一致的相关性。然而,对于单个病毒,所提供的d值可用于未来定量微生物风险评估(QMRA),并支持在流行地区病毒性疾病急性暴发的情况下采购天然肠衣的应急方案和预防措施。
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引用次数: 0
Maedi infection modulates oncogenic and inflammatory signaling in ovine pulmonary adenomatosis through TLR4/NF-κB and JAK2/STAT3 pathways: A Trojan horse mechanism Maedi感染通过TLR4/NF-κB和JAK2/STAT3通路调节羊肺腺瘤病的致癌和炎症信号:特洛伊木马机制
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2026-01-26 DOI: 10.1016/j.vetmic.2026.110906
İsmail Bolat , Enver Beytut , Yavuz Selim Sağlam , Emin Karakurt , Nüvit Coşkun , Selim Çomakli , Berrah Gözegi̇r , Tuba Karaarslan , Merve Bolat , Betül Orhan
Ovine pulmonary adenomatosis (OPA) is a contagious pulmonary tumor of sheep caused by Jaagsiekte sheep retrovirus, whereas Maedi is a chronic lentiviral infection characterized by persistent pulmonary inflammation. Although both diseases affect the lung, their interaction during natural co-infection remains poorly understood. This study investigated how chronic Maedi infection may influence inflammatory, oncogenic, and apoptotic signaling pathways in OPA-affected lung tissue. Lung samples from naturally infected sheep were classified by PCR and histopathological examination into Maedi (n = 6), OPA (n = 6), and Maedi+OPA co-infection (n = 6) groups. Key inflammatory, oncogenic, and apoptotic markers were evaluated at the protein and transcript levels. Maedi and mixed infection groups showed increased activation of the TLR4/NF-κB pathway and elevated pro-inflammatory cytokine expression compared with OPA alone. These changes were associated with significant alterations in apoptotic markers, including increased Bax and Caspase-3 expression and decreased Bcl-2 levels (p < 0.05). In contrast, OPA samples exhibited higher activity of JAK2/STAT3 and PI3K/AKT/mTOR signaling pathways, which appeared reduced under Maedi-associated conditions. Overall, these findings suggest that chronic Maedi infection may modulate the pulmonary microenvironment by influencing inflammatory, apoptotic, and oncogenic signaling pathways in OPA. This immunomodulatory interaction may be relevant for understanding host–virus dynamics in naturally occurring virus-induced lung tumors.
绵羊肺腺瘤病(OPA)是由绵羊Jaagsiekte逆转录病毒引起的绵羊传染性肺肿瘤,而Maedi是一种以持续肺部炎症为特征的慢性慢病毒感染。虽然这两种疾病都影响肺部,但它们在自然共感染期间的相互作用仍然知之甚少。本研究探讨慢性Maedi感染如何影响opa影响肺组织的炎症、致癌和凋亡信号通路。自然感染羊肺标本经PCR和组织病理学检查分为Maedi组(n = 6)、OPA组(n = 6)和Maedi+OPA合并感染组(n = 6)。在蛋白质和转录水平上评估关键的炎症、致癌和凋亡标志物。与单纯OPA组相比,Maedi组和混合感染组TLR4/NF-κB通路激活增加,促炎细胞因子表达升高。这些变化与凋亡标志物的显著改变相关,包括Bax和Caspase-3表达增加和Bcl-2水平降低(p <; 0.05)。相比之下,OPA样品表现出更高的JAK2/STAT3和PI3K/AKT/mTOR信号通路活性,这些信号通路在maedii相关条件下出现降低。总之,这些发现表明慢性Maedi感染可能通过影响OPA的炎症、凋亡和致癌信号通路来调节肺微环境。这种免疫调节相互作用可能与理解自然发生的病毒诱导的肺肿瘤的宿主-病毒动力学有关。
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引用次数: 0
TANK-binding Kinase 1 regulates the intracellular survival of Brucella TANK-binding Kinase 1调控布鲁氏菌的细胞内存活
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2026-01-25 DOI: 10.1016/j.vetmic.2026.110904
Zhiqiang Li , Shuli Wang , Ruirui Li , Yanyan Cui , Jinliang Zhang , Junfang Hao , Huijun Zhang , Qifeng Li , Hui Zhang
Brucella, the causative agent of brucellosis, is a globally important intracellular pathogen. TANK-binding kinase 1 (TBK1), a key component of the type I interferon induction pathway, is known to play a critical role in controlling intracellular bacterial infections. However, the function of TBK1 during Brucella infection remains poorly understood. In this study, we investigated the role of TBK1during Brucella infection. We observed that Brucella infection upregulates TBK1 expression in macrophages. Using TBK1-targeting small interfering RNAs (siRNAs) and overexpression approaches, we examined how TBK1 regulates the intracellular survival of Brucella. Results demonstrated that TBK1 knockdown significantly promoted intracellular bacterial growth and reduced the production of the pro-inflammatory cytokines IL-1β, IL-6, TNF-α, and IFN-γ. Conversely, TBK1 overexpression inhibited intracellular Brucella growth and enhanced the secretion of these cytokines. Moreover, Brucella infection also stimulated TBK1 expression in mice, and TBK1 knockout promoted bacterial survival in vivo. Furthermore, during Brucella infection, TBK1 inhibition significantly suppressed NF-κB activity, whereas TBK1 overexpression enhanced it. Collectively, our findings demonstrated that TBK1 acts as an essential regulator of Brucella survival and growth both in vitro and in vivo. The mechanism by which TBK1 induces pro-inflammatory cytokines and activates NF-κB warrants further investigation to elucidate its role in bacterial intracellular persistence.
布鲁氏菌是布鲁氏菌病的病原体,是一种全球性的重要细胞内病原体。坦克结合激酶1 (TANK-binding kinase 1, TBK1)是I型干扰素诱导途径的关键组分,已知在控制细胞内细菌感染中起关键作用。然而,TBK1在布鲁氏菌感染期间的功能仍然知之甚少。在这项研究中,我们研究了tbk1在布鲁氏菌感染中的作用。我们观察到布鲁氏菌感染上调巨噬细胞中TBK1的表达。利用TBK1靶向小干扰rna (sirna)和过表达方法,我们研究了TBK1如何调节布鲁氏菌的细胞内存活。结果表明,TBK1敲低显著促进细胞内细菌生长,减少促炎细胞因子IL-1β、IL-6、TNF-α和IFN-γ的产生。相反,TBK1过表达抑制了细胞内布鲁氏菌的生长并增强了这些细胞因子的分泌。此外,布鲁氏菌感染也刺激了TBK1在小鼠体内的表达,TBK1敲除促进了细菌在体内的存活。此外,在布鲁氏菌感染期间,TBK1抑制显著抑制NF-κB活性,而TBK1过表达则增强NF-κB活性。总之,我们的研究结果表明TBK1在体外和体内都是布鲁氏菌存活和生长的重要调节剂。TBK1诱导促炎细胞因子和激活NF-κB的机制有待进一步研究,以阐明其在细菌细胞内持久性中的作用。
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引用次数: 0
Genomic analysis of a porcine exudative epidermitis outbreak caused by Staphylococcus hyicus 猪渗出性表皮炎爆发的猪葡萄球菌的基因组分析
IF 2.7 2区 农林科学 Q3 MICROBIOLOGY Pub Date : 2026-01-23 DOI: 10.1016/j.vetmic.2026.110883
Alec Truswell , David Jordan , Stanley Pang , Tanya Cherrington , David J. Hampson , John Blinco , Sandy Adsett , Rebecca Abraham , Marc Stegger , Sam Abraham
Exudative epidermitis (EE) causes substantial morbidity and mortality in piglets. This study investigated the microbial ecology, antimicrobial resistance (AMR), and genomic diversity of Staphylococcus hyicus associated with an EE outbreak in an Australian piggery.
Lesion swabs from 20 affected piglets yielded 160 bacterial isolates (including S. hyicus and cohabiting species). Isolates underwent species identification, antimicrobial susceptibility testing, and whole-genome sequencing (WGS) of S. hyicus for AMR/virulence gene profiling and core-genome SNP analysis to assess genomic relatedness.
S. hyicus predominated among lesion isolates. Phenotypic testing showed varied AMR, with frequent resistance to erythromycin and tetracycline. WGS of 27 S. hyicus isolates identified five distinct genotypic AMR profiles, including combinations spanning multiple drug classes. All S. hyicus carried the exfoliative toxin gene shetA, and 24 also carried exhD.
Core-genome analysis indicated a highly clonal outbreak: 24/27 genomes differed by 0 core SNPs, with the remaining three closely related. Despite this clonality, resistance gene carriage varied across isolates. Consequently, reliance on a single colony to represent an outbreak could understate resistance and overstate treatability.
These findings support routine multi-isolate sampling to capture within-clone AMR variability, bolster antimicrobial selection during EE management, and inform consideration of autogenous vaccines targeting dominant outbreak clones.
渗出性表皮炎(EE)在仔猪中引起大量的发病率和死亡率。本研究调查了与澳大利亚猪场EE暴发相关的葡萄球菌的微生物生态、抗菌素耐药性(AMR)和基因组多样性。从20头受感染仔猪的病变拭子中分离出160株细菌(包括葡萄球菌和同居种)。对分离株进行物种鉴定、药敏试验和全基因组测序(WGS),进行抗菌素耐药性/毒力基因分析和核心基因组SNP分析,以评估基因组亲缘性。病株中以Hyicus为主。表型检测显示不同的AMR,常见的耐红霉素和四环素。27株hyicus菌株的WGS鉴定出5种不同的基因型AMR谱,包括跨越多种药物类别的组合。所有hyicus均携带剥脱毒素基因shetA,其中24株携带exhD基因。核心基因组分析表明这是一次高度克隆爆发:24/27个基因组差异0个核心snp,其余3个密切相关。尽管存在这种克隆性,但不同菌株间的抗性基因携带情况不同。因此,依靠单一菌落来代表爆发可能会低估耐药性和夸大可治疗性。这些发现支持常规多分离物取样以捕获克隆内抗菌素耐药性变异性,支持EE管理期间的抗菌药物选择,并为考虑针对优势爆发克隆的自体疫苗提供信息。
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引用次数: 0
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Veterinary microbiology
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