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Multidrug-Resistant and Hypervirulent Listeria monocytogenes in Foods and Food-Processing Environments in Southern Brazil. 巴西南部食品和食品加工环境中的多药耐药和高毒单核细胞增生李斯特菌。
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2026-01-29 DOI: 10.1016/j.micpath.2026.108338
Itiane Barcellos Jaskulski, Leticia Klein Scheik, Isabela Schneid Kroning, Tassiana Ramires, Natalie Rauber Kleinübing, Luiz Gustavo Bach, Giovana Wink Faleiro, Graciela Völz Lopes, Wladimir Padilha da Silva

Listeria monocytogenes is a major foodborne pathogen responsible for listeriosis, a severe disease with high fatality rates that typically requires antimicrobial therapy. This study aimed to characterize antimicrobial resistance and the presence of hypervirulence-associated LIPI-3 and LIPI-4 markers in L. monocytogenes from foods and food-processing environments in southern Brazil, and to evaluate the genetic relatedness of multidrug-resistant (MDR) isolates using Pulsed-Field Gel Electrophoresis (PFGE). Among 82 isolates, resistance was observed to clindamycin (CLI, 48.7%), meropenem (MER, 29.3%), sulfamethoxazole/trimethoprim (SUT, 29.3%), rifampicin (RIF, 14.6%), erythromycin (ERY, 10.9%), tetracycline (TET, 8.5%), streptomycin (STR, 7.3%), and amikacin (AMK, 4.9%). All tetracycline-resistant isolates carried the tetM gene (7/7), and 85.7% (6/7) also carried the tetL gene. Among erythromycin-resistant isolates, the ermB gene was detected in 11.1% (1/9). Fifteen isolates (18.3%) showed multidrug resistance, with the ERY-CLI-RIF-MER-SUT-TET profile being the most prevalent. Regarding virulence, all 15 MDR isolates harbored LIPI-1 and LIPI-2 genes, whereas 60% of the isolates carried at least one of the hypervirulence-associated pathogenicity islands, LIPI-3 or LIPI-4, or both. MDR L. monocytogenes showed distinct PFGE patterns (n=15), indicating high genetic diversity, including among hypervirulent isolates. This study demonstrates the occurrence of L. monocytogenes isolates in foods and food-processing environments in southern Brazil that are resistant to clinically relevant antimicrobials, including multidrug resistance, and that also exhibit hypervirulent genotypes. The coexistence of antimicrobial resistance and hypervirulence in L. monocytogenes underscores the urgent need for continuous monitoring and control strategies to mitigate public health risks.

单核细胞增生李斯特菌是导致李斯特菌病的主要食源性病原体,李斯特菌病是一种具有高致死率的严重疾病,通常需要抗菌治疗。本研究旨在表征巴西南部食品和食品加工环境中单核增生乳杆菌的抗菌素耐药性和高毒力相关的LIPI-3和LIPI-4标记的存在,并利用脉冲场凝胶电泳(PFGE)评估多重耐药(MDR)分离株的遗传相关性。82株分离菌对克林霉素(CLI, 48.7%)、美罗培南(MER, 29.3%)、磺胺甲恶唑/甲氧苄啶(SUT, 29.3%)、利福平(RIF, 14.6%)、红霉素(ERY, 10.9%)、四环素(TET, 8.5%)、链霉素(STR, 7.3%)、阿米卡星(AMK, 4.9%)耐药。所有四环素耐药菌株均携带tetM基因(7/7),85.7%(6/7)同时携带tetL基因。在红霉素耐药菌株中,检测到ermB基因的占11.1%(1/9)。15株(18.3%)出现多药耐药,其中ERY-CLI-RIF-MER-SUT-TET菌株最为普遍。就毒力而言,所有15株MDR分离株都携带LIPI-1和LIPI-2基因,而60%的分离株携带至少一种高毒力相关致病性岛,即LIPI-3或LIPI-4,或两者兼有。MDR L. monocytogenes表现出不同的PFGE模式(n=15),表明具有高度的遗传多样性,包括在高毒力菌株之间。这项研究表明,在巴西南部的食品和食品加工环境中存在单核细胞增生乳杆菌分离株,它们对临床相关的抗菌素具有耐药性,包括多药耐药性,并且还表现出高毒力基因型。单核增生乳杆菌的抗微生物药物耐药性和高毒力共存,强调迫切需要持续监测和控制战略,以减轻公共卫生风险。
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引用次数: 0
Antimicrobial resistance and genomic characterization of Escherichia coli isolated from mink in northern China. 中国北方水貂分离株大肠埃希菌的耐药性及基因组特征分析
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2026-01-29 DOI: 10.1016/j.micpath.2026.108328
Hao Ni, Qing-Yu Hou, Chao Xu, Xue Leng, Xue-Min Li, Ya Qin, Shuo Liu, Meng-Ting Yang, Lu-Yao Tang, Yu-Zhe Sun, Quan Zhao, Hong-Bo Ni, Xiao-Xuan Zhang, Jing Jiang, Li-Hua Yang, He Ma

Escherichia coli (E. coli) is one of the most common commensal bacteria in the intestinal tract of humans and animals. It serves as a major reservoir of antimicrobial resistance genes and may facilitate their horizontal transfer among different hosts. In this study, 212 fecal samples were collected from mink across four northern provinces of China, a total of 110 E. coli isolates were recovered (isolation rate, 51.89 %). Preliminary antimicrobial screening was conducted using four clinically critical antibiotics, including ceftazidime (CAZ), polymyxin B (PMB), meropenem (MEM), and tigecycline (TGC), with CAZ resistance being the most prevalent, followed by PMB, MEM, and TGC. Further antimicrobial susceptibility testing against ten commonly used antibiotics in 49 representative isolates revealed universal multidrug resistance (MDR), including 100 % resistance to imipenem, tetracycline, enrofloxacin, florfenicol, and sulfamethoxazole. Genetic screening identified multiple resistance genes such as aac(3')-IIa, blaCTX-M, tet(A), and mcr-1. Conjugation assays demonstrated that CAZ resistance was the most transferable. Virulence profiling revealed a low prevalence of classical pathogenic virulence factors, with only six virulence gene types detected, consistent with the results of Galleria mellonella infection assays. Whole-genome sequencing of 41 representative isolates revealed 87 unique antibiotic resistance genes (ARGs) types spanning 14 antibiotic classes including alinically important determinants such as blaCTX-M, tet, and mcr, and 71 unique virulence genes assigned to 65 functions. Metagenomic analysis further identified diverse ARGs within the mink gut microbiota, with 21 shared between whole-genome and metagenomic sequencing. Correlation analysis suggested co-occurrence patterns among ARGs, virulence factor genes (VFGs), and mobile genetic elements (MGEs), particularly between ARGs and MGEs. Overall, mink-derived E. coli exhibited extensive MDR but limited classical pathogenic virulence, and the mink gut microbiota may represent an important reservoir and transmission hub for resistance genes in intensive farming ecosystems.

大肠杆菌(E. coli)是人类和动物肠道中最常见的共生细菌之一。它是抗菌素耐药基因的主要储存库,并可能促进它们在不同宿主之间的水平转移。本研究在中国北方四省采集水貂粪便212份,共分离出110株大肠杆菌,分离率为51.89%。对头孢他啶(CAZ)、多粘菌素B (PMB)、美罗培南(MEM)、替加环素(TGC) 4种临床关键抗生素进行初步筛选,结果显示,CAZ耐药率最高,其次为PMB、MEM、TGC。49株代表性分离株对10种常用抗生素的药敏试验显示普遍耐多药(MDR),包括对亚胺培南、四环素、恩诺沙星、氟苯尼考和磺胺甲恶唑的100%耐药。遗传筛选鉴定出多种耐药基因,如aac(3’)-IIa、blaCTX-M、tet(A)和mcr-1。偶联试验表明,CAZ抗性是最易转移的。毒力分析显示经典致病性毒力因子的流行率较低,仅检测到6种毒力基因类型,与mellonella感染分析的结果一致。41株代表性菌株的全基因组测序揭示了87种独特的抗生素耐药基因(ARGs)类型,跨越14种抗生素类别,包括重要的决定因素,如blaCTX-M, tet和mcr,以及71种独特的毒力基因,分配给65种功能。宏基因组分析进一步确定了水貂肠道微生物群中的多种ARGs,其中21种在全基因组测序和宏基因组测序之间共享。相关分析表明,ARGs、毒力因子基因(vfg)和移动遗传元件(MGEs)之间存在共现模式,尤其是ARGs和MGEs之间。总体而言,水貂来源的大肠杆菌表现出广泛的耐多药耐药性,但经典致病力有限,水貂肠道微生物群可能是集约化养殖生态系统中抗性基因的重要储存库和传播中心。
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引用次数: 0
A novel strategy based on serum metabolite-mediated interactions between the lung and gut microbiota to investigate the protective effect of Flos Farfarae against chronic bronchitis. 一种基于血清代谢物介导的肺和肠道微生物群相互作用的新策略来研究Farfarae对慢性支气管炎的保护作用。
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2026-01-29 DOI: 10.1016/j.micpath.2026.108337
Shuxian Wang, Hao Xu, Liyuan Nie, Zhixing Fu, Jingqi Zhao, Xuemei Qin, Zhenyu Li

Chronic bronchitis (CB) is a complex respiratory disease characterized by a persistent cough, dyspnea, and excessive sputum production. Flos Farfarae (FF), derived from the dried flower buds of Tussilago farfara L. (Asteraceae), has a long history of use in Traditional Chinese Medicine (TCM) for treating respiratory ailments. In our study, FF treatment significantly reduced serum interleukin 1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) in the CB rats, and hematoxylin and eosin (HE) staining of lung and colon tissues also indicated obvious reduction in inflammatory infiltrates. Additionally, we found that FF treatment markedly decreased the abundance of the lung bacterium Pseudomonas and the gut bacterium Roseburia. Bugbase analysis showed that FF was able to reduce the increased potentially pathogenic bacteria in the lung and gut microbiota of CB rats. Serum pseudo-targeted metabolomic analysis showed that FF significantly modulated 31 differential serum metabolites, including palmitoleic acid and indoxyl sulfate. Furthermore, correlation-based ensemble network analysis revealed that interactions between lung and gut microbiota were significantly increased in the CB rats. Similarly, interactions between lung microbiota and serum metabolites, as well as between gut microbiota and serum metabolites, were significantly enhanced. However, FF treatment significantly reduced these interactions. FF treatment not only alleviates the inflammatory state of rats with chronic bronchitis by modulating specific lung and gut microbiota and serum metabolites, but also may restore gut and lung microbial homeostasis by decreasing serum metabolite-mediated interactions between the lung and gut microbiota, thereby resulting in therapeutic effects in rats with CB. We systematically evaluated the efficacy of the traditional Chinese medicine FF in CB from the innovative perspective of serum metabolite-mediated interactions between lung and gut microbiota for the first time.

慢性支气管炎(CB)是一种复杂的呼吸系统疾病,以持续咳嗽、呼吸困难和痰多为特征。鸢尾花(fls Farfarae, FF)是从鸢尾科植物Tussilago farfara L. (Asteraceae)的干花蕾中提取的,在中医中用于治疗呼吸系统疾病已有很长的历史。在我们的研究中,FF处理显著降低了CB大鼠血清白细胞介素1β (IL-1β)、白细胞介素6 (IL-6)和肿瘤坏死因子α (TNF-α),肺和结肠组织苏木精和伊红(HE)染色也显示炎症浸润明显减少。此外,我们发现FF处理显著降低了肺部细菌假单胞菌和肠道细菌Roseburia的丰度。虫基分析表明,FF能够减少CB大鼠肺和肠道微生物群中潜在致病菌的增加。血清伪靶向代谢组学分析显示,FF对棕榈油酸和硫酸吲哚酚等31种血清代谢物有显著调节作用。此外,基于相关的集合网络分析显示,在CB大鼠中,肺和肠道微生物群之间的相互作用显著增加。同样,肺微生物群与血清代谢物之间、肠道微生物群与血清代谢物之间的相互作用也显著增强。然而,FF处理显著减少了这些相互作用。FF治疗不仅可以通过调节特定的肺和肠道微生物群和血清代谢物来缓解慢性支气管炎大鼠的炎症状态,还可以通过降低血清代谢物介导的肺和肠道微生物群之间的相互作用来恢复肠道和肺部的微生物稳态,从而对慢性支气管炎大鼠产生治疗作用。我们首次从血清代谢物介导的肺和肠道菌群相互作用的创新视角,系统评价中药FF对CB的疗效。
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引用次数: 0
Isolation, characterization and genomic analysis of three lytic bacteriophages (PBM) targeting Avian Pathogenic Escherichiacoli. 三种禽致病性大肠杆菌裂解噬菌体(PBM)的分离、鉴定及基因组分析
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2026-01-28 DOI: 10.1016/j.micpath.2026.108327
Saleha Masood, Muhammad Khan, Andleeb Khizar, Hira Niaz, Aqsa Ahsan, Amna Jalil, Fazal Adnan

Avian pathogenic Escherichia coli (APEC) cause significant economic losses in the poultry industry, further exacerbated by the growing number of multi-drug resistance pathogens that make treating infections more difficult. To combat this, the study presents two novel Schitoviridae phages (PBM-2 and PBM-3) and a novel Straboviridae phage (PBM-1) that show significant and highly specific lytic activity against APEC strains. Moreover, the phages show significant lytic activity at MOI as low as 0.1 and show substantial thermal (4-45 °C) and acidic tolerance (pH 3-7). The PBM phages also show suitable growth parameters, with high adsorption rates (9-15 min), relatively short latent periods (20-25 min), and a good burst size (∼100 per cell). The genome sizes for the PBM phages are around 121 kb for PBM-1 and 72 kb for PBM-2 and PBM-3, with 194, 84 and 83 predicted genes, respectively. Comparative genomic analysis revealed a high sequence similarity between PBM-2 and PBM-3. Further analysis showed a high degree of relatedness of PBM-1 with Escherichia phage EPIMAM01 and Escherichia phage HP3, as well as PBM-2 and PBM-3 with Escherichia phage UE-S5b, Enterobacteria phage Bp4. Furthermore, no genes associated with antibiotic resistance, lysogeny, or known virulence factors were detected, supporting their suitability for therapeutic use. The isolation and characterization of these novel phages presents an opportunity to develop effective phage therapies against avian colibacillosis.

禽致病性大肠杆菌(APEC)给家禽业造成了重大的经济损失,而越来越多的耐多药病原体使治疗感染变得更加困难,这进一步加剧了这种损失。为了解决这个问题,该研究提出了两种新的血吸虫病毒科噬菌体(PBM-2和PBM-3)和一种新的Straboviridae噬菌体(PBM-1),它们对APEC菌株具有显著和高度特异性的裂解活性。此外,噬菌体在MOI低至0.1时表现出显著的裂解活性,并表现出良好的耐热性(4-45°C)和耐酸性(pH 3-7)。PBM噬菌体也显示出合适的生长参数,具有高吸附率(9-15分钟),相对较短的潜伏期(20-25分钟)和良好的破裂大小(每个细胞约100个)。PBM-1噬菌体的基因组大小约为121 kb, PBM-2和PBM-3噬菌体的基因组大小约为72 kb,分别有194、84和83个预测基因。比较基因组分析显示,PBM-2和PBM-3序列高度相似。进一步分析发现,PBM-1与噬菌体EPIMAM01、HP3具有高度亲缘性,PBM-2、PBM-3与噬菌体e - s5b、肠杆菌Bp4具有高度亲缘性。此外,没有检测到与抗生素耐药性、溶原性或已知毒力因子相关的基因,支持其治疗用途的适用性。这些新型噬菌体的分离和表征为开发针对禽大肠杆菌病的有效噬菌体疗法提供了机会。
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引用次数: 0
Natural supplements effectively suppress Helicobacter pylori colonization and improve gastric antioxidant and antiinflammatory responses in an indomethacin-induced ulcer model. 在吲哚美辛诱导的溃疡模型中,天然补充剂有效抑制幽门螺杆菌定植,改善胃抗氧化和抗炎反应。
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2026-01-28 DOI: 10.1016/j.micpath.2026.108320
Elif Aydin, Ayse Kocak Sezgin, Meliha Koldemir Gunduz, Birkan Açikgoz, Güllü Kaymak, Sercan Simsek
<p><strong>Background: </strong>The coexistence of Helicobacter pylori (H. pylori) infection and use of non-steroidal anti-inflammatory drugs (NSAIDs) is very common in clinics and they act together to worsen the gastric damage. The growing resistance to antibiotics and the side effects of the eradication regimens support the use of multi-target supportive strategies. The study aimed to determine the antibacterial, antibiofilm, antioxidant, and anti-inflammatory effects of three natural supplements as well as their effect on HIF-1α and TGF-β expression in a rat model of indomethacin-induced H. pylori gastric ulcer.</p><p><strong>Methods: </strong>The in vitro anti-H. pylori activity of the two formulations (Nitro-plus and Sunset) was evaluated by determining the minimum inhibitory concentration (MIC) and using resazurin microdilution methods, along with antibiofilm assays conducted in 96-well plates. The experiment was carried out on female Wistar rats, which were allocated to six groups: healthy control, indomethacin-induced ulcer, H. pylori + gastritis ulcer, gastritis ulcer + natural supplements, H. pylori + gastritis ulcer + natural supplements, and H. pylori + gastritis ulcer + standard triple therapy. Indomethacin (5 mg/kg) was the agent used for inducing ulcers, and the presence of H. pylori was determined by testing for fecal antigen and urease. After a 30-day period of different treatments, the gastric tissues were assessed for the following parameters: urease activity, bacterial load (CFU/g), IL-1β and IL-10 levels (ELISA), HIF-1α and TGF-β expression (qPCR), as well as total antioxidant status (TAS) and total oxidant status (TOS) measurements, malondialdehyde (MDA), catalase (CAT), and glutathione (GSH) levels, and histopathology.</p><p><strong>Results: </strong>Nitro-plus and Sunset presented notable anti-H. pylori activities (MIC 2.2 and 0.406 mg/mL without resazurin) and also antibiofilm activities, with the inhibition of biofilm biomass being ∼58 % and ∼47 %, respectively. In vivo, natural supplements, in decreasing the gastric burden of H. pylori, reducing the urease activity, lowering the levels of IL-1β and HIF-1α, and raising the level of IL-10 as compared to the untreated H. pylori + ulcer group, had effects comparable to triple therapy in several parameters. The TOS and MDA levels were lowered while the TAS, CAT and GSH levels were increased, thus the histological scores were also improved due to the attenuation of inflammation, neutrophil activation, and bacterial colonization.</p><p><strong>Conclusion: </strong>The use of multi-component natural supplements that addressed bacterial load, biofilm formation, oxidative stress, inflammatory cytokines and hypoxia-related pathways reduced the effects of indomethacin and H. pylori in causing gastric damage and made the supplements a good candidate for adjunctive support in standard eradication regimens. The clinical trials should be controlled and conducted to confirm the translat
背景:幽门螺杆菌(h.p ylori)感染与非甾体抗炎药(NSAIDs)共存是临床上非常常见的,它们共同作用加重了胃的损害。日益增长的抗生素耐药性和根除方案的副作用支持使用多靶点支持策略。本研究旨在检测三种天然补品的抗菌、抗生物膜、抗氧化、抗炎作用以及对吲哚美辛致幽门螺杆菌胃溃疡大鼠模型中HIF-1α和TGF-β表达的影响。方法:采用体外抗h。通过测定最低抑菌浓度(MIC)和reazurin微量稀释法,以及在96孔板上进行的抗生素膜测定,评估了两种配方(nitron -plus和Sunset)的幽门螺杆菌活性。实验选用雌性Wistar大鼠,分为健康对照组、吲哚美辛致溃疡组、幽门螺杆菌+胃炎溃疡组、胃炎溃疡+天然补充剂组、幽门螺杆菌+胃炎溃疡+天然补充剂组、幽门螺杆菌+胃炎溃疡+标准三联疗法组。用吲哚美辛(5 mg/kg)诱导溃疡,通过粪便抗原和脲酶检测幽门螺杆菌的存在。经过30天的不同处理后,对胃组织进行以下参数评估:脲酶活性、细菌负荷(CFU/g)、IL-1β和IL-10水平(ELISA)、HIF-1α和TGF-β表达(qPCR)、总抗氧化状态(TAS)和总氧化状态(TOS)测量、丙二醛(MDA)、过氧化氢酶(CAT)和谷胱甘肽(GSH)水平以及组织病理学。结果:硝基+和日落具有显著的抗h作用。在不含resazurin的情况下,其幽门螺杆菌活性(MIC为2.2和0.406 mg/mL)和抗生物膜活性,对生物膜生物量的抑制率分别为58%和47%。在体内,与未治疗的幽门螺杆菌+溃疡组相比,天然补充剂在减轻幽门螺杆菌胃负荷、降低脲酶活性、降低IL-1β和HIF-1α水平以及提高IL-10水平方面的效果与三联疗法相当。TOS和MDA水平降低,TAS、CAT和GSH水平升高,炎症、中性粒细胞活化和细菌定植的减弱也提高了组织学评分。结论:使用多组分天然补充剂可解决细菌负荷、生物膜形成、氧化应激、炎症因子和缺氧相关途径,减少吲哚美辛和幽门螺杆菌对胃损伤的影响,使其成为标准根除方案中辅助支持的良好候选补充剂。临床试验应加以控制和实施,以确认其与翻译的相关性。
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引用次数: 0
Virulence and antimicrobial resistance gene profiling in multidrug-resistant Pseudomonas aeruginosa with evaluation of levofloxacin and amikacin therapy 多重耐药铜绿假单胞菌的毒力和耐药基因分析与左氧氟沙星和阿米卡星治疗的评价
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2026-01-27 DOI: 10.1016/j.micpath.2026.108334
Sivaperumal Pitchiah , Dhanraj Ganapathy , Kannan Kamala
Multidrug-resistant (MDR) Pseudomonas aeruginosa is an opportunistic pathogen responsible for severe oral and hospital-acquired infections due to its strong biofilm-forming ability and multidrug resistance (MDR). This study investigated the virulence and resistance of P. aeruginosa isolated from subgingival biofilms and evaluated the antibiofilm activity of levofloxacin (LVX) and amikacin (AMK), individually and in combination. From 157 subgingival samples, 14 isolates were confirmed as P. aeruginosa, all resistant to antibiotic classes, indicating MDR status. Susceptibility testing revealed complete resistance to amoxiclav (100 %) and high resistance to ceftazidime (85.7 %), with moderate resistance to ciprofloxacin and gentamicin. The isolate with the highest biofilm-forming ability was used for further analysis. Crystal violet quantification demonstrated that LVX and AMK inhibited biofilm biomass by 39.9 % and 59.9 % at 24 h and by 70 % and 75.1 % at 48 h, respectively, whereas their combination achieved 96.2 % inhibition at 48 h. Live cell inhibition assessed by acridine orange staining showed that the LVX–AMK combination resulted in 97 ± 1.2 % reduction of viable biofilm cells at 48 h (p < 0.001). qRT-PCR analysis revealed 0.2–0.4-fold downregulation of virulence genes (fadA, toxA, lasB, algD, exoS) in the combination group. Structural modeling and Ramachandran analysis showed conserved and stable protein regions. These findings suggest that combined LVX–AMK therapy exhibits synergistic antibiofilm and anti-virulence effects against MDR P. aeruginosa, shows potential for treating biofilm-associated infections.
耐多药铜绿假单胞菌具有很强的生物膜形成能力和耐多药性,是导致严重口腔感染和医院获得性感染的条件致病菌。本研究研究了从龈下生物膜分离的铜绿假单胞菌(P. aeruginosa)的毒力和耐药性,并对左氧氟沙星(LVX)和阿米卡星(AMK)单独和联合使用的抗生物膜活性进行了评价。157份龈下样本中,14株被确认为铜绿假单胞菌,均对抗生素耐药,表明处于耐多药状态。药敏试验显示,对阿莫昔拉完全耐药(100% %),对头孢他啶高耐药(85.7% %),对环丙沙星和庆大霉素耐药中等。采用生物膜形成能力最强的分离物进行进一步分析。结晶紫定量测定结果表明,LVX和AMK在24 h时对生物膜生物量的抑制作用分别为39.9 %和59.9 %,在48 h时对生物膜生物量的抑制作用分别为70 %和75.1 %,而它们的组合在48 h时对生物膜生物量的抑制作用为96.2 %。吖啶橙染色评估的活细胞抑制显示LVX-AMK联合在48 h时可使活生物膜细胞减少97 ± 1.2 % (p <; 0.001)。qRT-PCR分析显示,联合用药组毒力基因(fadA、toxA、lasB、algD、exoS)下调0.2 - 0.4倍。结构建模和Ramachandran分析显示保守和稳定的蛋白质区域。这些发现表明,LVX-AMK联合治疗对耐多药铜绿假单胞菌具有协同的抗生物膜和抗毒作用,具有治疗生物膜相关感染的潜力。
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引用次数: 0
Comparative assessment of ΔarnA and ΔugdΔarnA mutants of Aeromonas dhakensis as live attenuated vaccine candidates: implications for polymyxin resistance and virulence attenuation. 达肯气单胞菌ΔarnA和ΔugdΔarnA突变体作为减毒活疫苗候选株的比较评估:对多粘菌素耐药性和毒力衰减的影响
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2026-01-26 DOI: 10.1016/j.micpath.2026.108331
Xuesong Li, Mengqi Wang, Zihao Di, Yamei Xu, Yukun Wu, Shuai Ye, Aodi Yi, Guiying Guo, Lixia Fan, Nuo Yang, Jiping Zheng

Aeromonas dhakensis is an emerging pathogen responsible for infections in humans, livestock, and aquatic species, posing a threat to public health and aquaculture. This study investigates the roles of two critical genes, arnA and ugd, which are involved in polymyxin resistance, by creating single (ΔarnA) and double (ΔugdΔarnA) deletion mutants in A. dhakensis. The mutants showed impaired motility, increased sensitivity to polymyxin, and altered biofilm formation. Virulence was reduced in zebrafish models, with ΔarnA exhibiting a 2.03-fold increase in median lethal dose (LD50), and ΔugdΔarnA showing a 7.13-fold increase. Immunization with these mutants provided significant protection, with survival rates of 65 % and 40 %, respectively, after challenge with the wild-type isolate, compared to the control group. These results underscore the critical roles of arnA and ugd in polymyxin resistance and virulence, highlighting their potential as targets for vaccine development in aquaculture disease control.

达肯气单胞菌是一种新兴病原体,可导致人类、牲畜和水生物种感染,对公共卫生和水产养殖构成威胁。本研究通过创建单(ΔarnA)和双(ΔugdΔarnA)缺失突变体,研究了两个参与多粘菌素抗性的关键基因arnA和ugd的作用。突变体表现出运动性受损,对多粘菌素的敏感性增加,生物膜形成改变。斑马鱼模型的毒力降低,ΔarnA的中位致死剂量(LD50)增加了2.03倍,ΔugdΔarnA的中位致死剂量增加了7.13倍。这些突变体免疫提供了显著的保护,与对照组相比,野生型分离物攻击后的存活率分别为65 %和40 %。这些结果强调了arnA和ugd在多粘菌素耐药性和毒力中的关键作用,突出了它们作为水产养殖疾病控制疫苗开发靶点的潜力。
{"title":"Comparative assessment of ΔarnA and ΔugdΔarnA mutants of Aeromonas dhakensis as live attenuated vaccine candidates: implications for polymyxin resistance and virulence attenuation.","authors":"Xuesong Li, Mengqi Wang, Zihao Di, Yamei Xu, Yukun Wu, Shuai Ye, Aodi Yi, Guiying Guo, Lixia Fan, Nuo Yang, Jiping Zheng","doi":"10.1016/j.micpath.2026.108331","DOIUrl":"https://doi.org/10.1016/j.micpath.2026.108331","url":null,"abstract":"<p><p>Aeromonas dhakensis is an emerging pathogen responsible for infections in humans, livestock, and aquatic species, posing a threat to public health and aquaculture. This study investigates the roles of two critical genes, arnA and ugd, which are involved in polymyxin resistance, by creating single (ΔarnA) and double (ΔugdΔarnA) deletion mutants in A. dhakensis. The mutants showed impaired motility, increased sensitivity to polymyxin, and altered biofilm formation. Virulence was reduced in zebrafish models, with ΔarnA exhibiting a 2.03-fold increase in median lethal dose (LD<sub>50</sub>), and ΔugdΔarnA showing a 7.13-fold increase. Immunization with these mutants provided significant protection, with survival rates of 65 % and 40 %, respectively, after challenge with the wild-type isolate, compared to the control group. These results underscore the critical roles of arnA and ugd in polymyxin resistance and virulence, highlighting their potential as targets for vaccine development in aquaculture disease control.</p>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"213 ","pages":"108331"},"PeriodicalIF":3.5,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Mechanism of tea saponin in alleviating intestinal damage induced by E. coli infection via the NF-κB/NLRP3 pathway 茶皂素通过NF-κB/NLRP3通路减轻大肠杆菌感染引起的肠道损伤的机制
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2026-01-26 DOI: 10.1016/j.micpath.2026.108326
Bo Zhang , Bo Liao , Fangjie Li , Yanhong Lv , Rong Liao , Dengyao Xu , Rou Sang , Ke Li , Aiguo Xin
Pathogenic Escherichia coli is a common zoonotic pathogen that can cause host diarrhea, edema, and mortality. Tea saponin (Ts) exhibits significant anti-inflammatory and antioxidant properties. However, its potential to mitigate acute intestinal injury caused by pathogenic E. coli remains unclear. This research aimed to investigate the protective effects of Ts against inflammatory pathological damage induced by E. coli and to elucidate the underlying molecular mechanisms. Four experimental groups were established: control, E. coli, E. coli + Ts, and E. coli + MCC950 (a selective NLRP3 inhibitor). Inflammatory pathological damage in the mouse colon was assessed through HE staining, analysis of intestinal barrier markers (ZO-1, Occludin, and Claudin-1), ELISA of inflammatory factors, and analysis of oxidative stress markers. The expression of key apoptosis-related genes and NF-κB/NLRP3 pathway genes was detected using RT-PCR. Immunohistochemistry and Western blot were employed to analyze the expression of apoptosis-related proteins (Bcl-2 and Bax), activated forms of Caspases (Cleaved Caspase-1, Cleaved Caspase-3, Cleaved Caspase-8), tight junction proteins (ZO-1, Occludin, and Claudin-1), and NF-κB/NLRP3 pathway proteins in mouse colon tissues. E. coli infection induced severe histopathological changes and intestinal barrier dysfunction in colon tissues and activated the NF-κB/NLRP3 signaling pathway. This activation significantly increased the expression of pro-apoptotic genes Bax, Caspase-8, and Caspase-3, as well as the levels of their cleaved (active) forms, while markedly decreasing the expression of Bcl-2, thereby promoting apoptosis. Ts treatment notably ameliorated colon pathological injury, effectively regulated the expression of apoptosis-related genes, and significantly suppressed the transcription levels of NF-κB, NLRP3, Caspase-1, IL-1β, IL-18, and TNF-α within the NF-κB/NLRP3 signaling pathway. Furthermore, Ts treatment significantly reduced the protein levels of cleaved Caspase-1, cleaved Caspase-3, and cleaved Caspase-8, and restored the expression of ZO-1, Occludin, and Claudin-1. Ts effectively inhibits inflammatory responses and cell apoptosis induced by E. coli by modulating the NF-κB/NLRP3 signaling pathway, and maintaining intestinal barrier integrity via regulating tight junction proteins, ultimately alleviating colon damage in mouse.
致病性大肠杆菌是一种常见的人畜共患病原体,可引起宿主腹泻、水肿和死亡。茶皂素(Ts)具有显著的抗炎和抗氧化特性。然而,其减轻致病性大肠杆菌引起的急性肠道损伤的潜力尚不清楚。本研究旨在探讨Ts对大肠杆菌引起的炎性病理损伤的保护作用,并阐明其分子机制。建立对照组、大肠杆菌组、大肠杆菌+ Ts组和大肠杆菌+ MCC950(一种选择性NLRP3抑制剂)4个实验组。通过HE染色、肠屏障标志物(ZO-1、Occludin、Claudin-1)分析、炎症因子ELISA和氧化应激标志物分析,评估小鼠结肠炎性病理损伤。RT-PCR检测细胞凋亡相关关键基因及NF-κB/NLRP3通路基因的表达。采用免疫组织化学和Western blot方法分析小鼠结肠组织中凋亡相关蛋白(Bcl-2和Bax)、caspase活化形式(Cleaved Caspase-1、Cleaved Caspase-3、Cleaved Caspase-8)、紧密连接蛋白(ZO-1、Occludin和Claudin-1)和NF-κB/NLRP3通路蛋白的表达。大肠杆菌感染引起结肠组织严重的组织病理学改变和肠屏障功能障碍,并激活NF-κB/NLRP3信号通路。这种激活显著增加促凋亡基因Bax、Caspase-8和Caspase-3的表达及其裂解(活性)形式的水平,同时显著降低Bcl-2的表达,从而促进细胞凋亡。Ts治疗可显著改善结肠病理性损伤,有效调节凋亡相关基因表达,显著抑制NF-κB/NLRP3信号通路中NF-κB、NLRP3、Caspase-1、IL-1β、IL-18、TNF-α的转录水平。此外,Ts处理显著降低了cleaved Caspase-1、cleaved Caspase-3和cleaved Caspase-8的蛋白水平,恢复了ZO-1、Occludin和Claudin-1的表达。Ts通过调节NF-κB/NLRP3信号通路,有效抑制大肠杆菌诱导的炎症反应和细胞凋亡,并通过调节紧密连接蛋白维持肠道屏障的完整性,最终减轻小鼠结肠损伤。
{"title":"Mechanism of tea saponin in alleviating intestinal damage induced by E. coli infection via the NF-κB/NLRP3 pathway","authors":"Bo Zhang ,&nbsp;Bo Liao ,&nbsp;Fangjie Li ,&nbsp;Yanhong Lv ,&nbsp;Rong Liao ,&nbsp;Dengyao Xu ,&nbsp;Rou Sang ,&nbsp;Ke Li ,&nbsp;Aiguo Xin","doi":"10.1016/j.micpath.2026.108326","DOIUrl":"10.1016/j.micpath.2026.108326","url":null,"abstract":"<div><div>Pathogenic <em>Escherichia coli</em> is a common zoonotic pathogen that can cause host diarrhea, edema, and mortality. Tea saponin (Ts) exhibits significant anti-inflammatory and antioxidant properties. However, its potential to mitigate acute intestinal injury caused by pathogenic <em>E. coli</em> remains unclear. This research aimed to investigate the protective effects of Ts against inflammatory pathological damage induced by <em>E. coli</em> and to elucidate the underlying molecular mechanisms. Four experimental groups were established: control, <em>E. coli</em>, <em>E. coli</em> + Ts, and <em>E. coli</em> + MCC950 (a selective NLRP3 inhibitor). Inflammatory pathological damage in the mouse colon was assessed through HE staining, analysis of intestinal barrier markers (ZO-1, Occludin, and Claudin-1), ELISA of inflammatory factors, and analysis of oxidative stress markers. The expression of key apoptosis-related genes and NF-κB/NLRP3 pathway genes was detected using RT-PCR. Immunohistochemistry and Western blot were employed to analyze the expression of apoptosis-related proteins (Bcl-2 and Bax), activated forms of Caspases (Cleaved Caspase-1, Cleaved Caspase-3, Cleaved Caspase-8), tight junction proteins (ZO-1, Occludin, and Claudin-1), and NF-κB/NLRP3 pathway proteins in mouse colon tissues. <em>E. coli</em> infection induced severe histopathological changes and intestinal barrier dysfunction in colon tissues and activated the NF-κB/NLRP3 signaling pathway. This activation significantly increased the expression of pro-apoptotic genes Bax, Caspase-8, and Caspase-3, as well as the levels of their cleaved (active) forms, while markedly decreasing the expression of Bcl-2, thereby promoting apoptosis. Ts treatment notably ameliorated colon pathological injury, effectively regulated the expression of apoptosis-related genes, and significantly suppressed the transcription levels of NF-κB, NLRP3, Caspase-1, IL-1β, IL-18, and TNF-α within the NF-κB/NLRP3 signaling pathway. Furthermore, Ts treatment significantly reduced the protein levels of cleaved Caspase-1, cleaved Caspase-3, and cleaved Caspase-8, and restored the expression of ZO-1, Occludin, and Claudin-1. Ts effectively inhibits inflammatory responses and cell apoptosis induced by <em>E. coli</em> by modulating the NF-κB/NLRP3 signaling pathway, and maintaining intestinal barrier integrity via regulating tight junction proteins, ultimately alleviating colon damage in mouse.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"213 ","pages":"Article 108326"},"PeriodicalIF":3.5,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146081251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Risk factors for sputum smear-positive in COPD patients first diagnosed with active tuberculosis. 首次诊断为活动性肺结核的COPD患者痰涂片阳性的危险因素。
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2026-01-25 DOI: 10.1016/j.micpath.2026.108319
Daoyan Tang, Jing Yang, Yongxian Zhang, Jian-Qing He

Objectives: The purpose of this study was to determine significant clinical risk factors for sputum smear-positivity in Chronic Obstructive Pulmonary Disease (COPD) patients who were also diagnosed with active tuberculosis.

Methods: A total of 776 patients diagnosed with COPD combined with active tuberculosis at West China Hospital of Sichuan University were retrospectively included. Of these, 527 were sputum smear-negative and 249 were sputum smear-positive at first diagnosis. Baseline data, routine blood and biochemical indices were compared between the two groups. Logistic regression was used to investigate the risk factors for sputum smear-positivity in COPD patients with active tuberculosis.

Results: Compared with those in the sputum smear-negative group, patients in the sputum smear-positive group had lower Body Mass Index (BMI), and were more likely to have a history of significant alcohol consumption (p < 0.05). Patients with chronic kidney disease and cardiovascular disease had lower risk of sputum smear positivity (p < 0.05). The hemoglobin concentration, lymphocyte count and albumin levels were significantly lower and the neutrophil, monocyte and platelet counts, blood glucose levels and erythrocyte sedimentation rate were higher in the sputum smear-positive group than those in the sputum smear-negative group (p < 0.05). Multivariate logistic regression analysis showed that low BMI (OR:0.86; 95 %CI:0.79, 0.94;p = 0.001), alcohol consumption (OR:2.13; 95 %CI:1.15,3.93;p = 0.016), low albumin (OR:0.91; 95 %CI:0.85, 0.97;p = 0.003), and elevated neutrophils (OR:3.44; 95 %CI:1.23, 9.28;p = 0.019) were significant risk factors for sputum smear positivity in patients with COPD combined with active tuberculosis.

Conclusion: In patients with COPD and active tuberculosis, alcohol consumption history, increased neutrophil count, low BMI and low serum albumin concentration are significant risk factors for sputum smear positivity at initial diagnosis. These risk factors should prompt clinicians to consider sputum examination. Respiratory isolation may be needed based on individual assessment.

目的:本研究的目的是确定慢性阻塞性肺疾病(COPD)患者同时诊断为活动性肺结核的痰涂片阳性的重要临床危险因素。方法:回顾性分析四川大学华西医院诊断为慢性阻塞性肺病合并活动性肺结核的776例患者。其中527例痰涂片阴性,249例首次诊断时痰涂片阳性。比较两组患者的基线数据、血常规及生化指标。采用Logistic回归分析COPD合并活动性结核患者痰涂片阳性的危险因素。结果:与痰涂片阴性组相比,痰涂片阳性组患者体重指数(BMI)较低,且有明显饮酒史的可能性较大(p结论:慢性阻塞性肺病合并活动性肺结核患者,饮酒史、中性粒细胞计数增高、BMI低、血清白蛋白浓度低是初诊时痰涂片阳性的重要危险因素。这些危险因素应促使临床医生考虑进行痰液检查。可能需要根据个人评估进行呼吸隔离。
{"title":"Risk factors for sputum smear-positive in COPD patients first diagnosed with active tuberculosis.","authors":"Daoyan Tang, Jing Yang, Yongxian Zhang, Jian-Qing He","doi":"10.1016/j.micpath.2026.108319","DOIUrl":"10.1016/j.micpath.2026.108319","url":null,"abstract":"<p><strong>Objectives: </strong>The purpose of this study was to determine significant clinical risk factors for sputum smear-positivity in Chronic Obstructive Pulmonary Disease (COPD) patients who were also diagnosed with active tuberculosis.</p><p><strong>Methods: </strong>A total of 776 patients diagnosed with COPD combined with active tuberculosis at West China Hospital of Sichuan University were retrospectively included. Of these, 527 were sputum smear-negative and 249 were sputum smear-positive at first diagnosis. Baseline data, routine blood and biochemical indices were compared between the two groups. Logistic regression was used to investigate the risk factors for sputum smear-positivity in COPD patients with active tuberculosis.</p><p><strong>Results: </strong>Compared with those in the sputum smear-negative group, patients in the sputum smear-positive group had lower Body Mass Index (BMI), and were more likely to have a history of significant alcohol consumption (p < 0.05). Patients with chronic kidney disease and cardiovascular disease had lower risk of sputum smear positivity (p < 0.05). The hemoglobin concentration, lymphocyte count and albumin levels were significantly lower and the neutrophil, monocyte and platelet counts, blood glucose levels and erythrocyte sedimentation rate were higher in the sputum smear-positive group than those in the sputum smear-negative group (p < 0.05). Multivariate logistic regression analysis showed that low BMI (OR:0.86; 95 %CI:0.79, 0.94;p = 0.001), alcohol consumption (OR:2.13; 95 %CI:1.15,3.93;p = 0.016), low albumin (OR:0.91; 95 %CI:0.85, 0.97;p = 0.003), and elevated neutrophils (OR:3.44; 95 %CI:1.23, 9.28;p = 0.019) were significant risk factors for sputum smear positivity in patients with COPD combined with active tuberculosis.</p><p><strong>Conclusion: </strong>In patients with COPD and active tuberculosis, alcohol consumption history, increased neutrophil count, low BMI and low serum albumin concentration are significant risk factors for sputum smear positivity at initial diagnosis. These risk factors should prompt clinicians to consider sputum examination. Respiratory isolation may be needed based on individual assessment.</p>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":" ","pages":"108319"},"PeriodicalIF":3.5,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146064857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Immunological effects of coinfections with Toxoplasma gondii, Helicobacter pylori, and Epstein-Barr virus on anisakiasis associated phenotypes. 弓形虫、幽门螺杆菌和eb病毒共感染对异丝虫病相关表型的免疫学影响
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2026-01-24 DOI: 10.1016/j.micpath.2026.108325
Juan González-Fernández, Virginia Fernández-Fígares, Marta Rodero, Alvaro Daschner, Carmen Cuéllar

The hygiene hypothesis proposes that infections acquired through the fecal-oral route or contaminated food, such as Toxoplasma gondii, may protect against IgE-mediated allergic disorders. Epstein-Barr virus (EBV) has been negatively associated with atopy, while Anisakis simplex and Helicobacter pylori are associated with acute and chronic urticaria, respectively. This study aimed to explore the impact of coinfection status on anisakiasis-associated phenotypes. A total of 112 human subjects were categorized by Anisakis sensitization status and clinical phenotypes: 25 with gastroallergic anisakiasis (GAA), 64 with chronic urticaria (CU; of these, 32 sensitized to A. simplex [CU+]), and 23 controls without urticaria. Serum IgE against A. simplex and IgG against T. gondii, H. pylori, and EBV were measured to assess exposure and coinfection patterns. Serum cytokine levels of IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, IL-17A, and TGF-β were quantified using flow cytometry. T. gondii coinfection was significantly more prevalent in A. simplex-seropositive subjects (AK+) (95.3 %), whereas H. pylori prevalence was higher in CU patients (55.9 %). All CU+ patients showed coinfection with H. pylori and triple coinfection (A. simplex/T. gondii/H. pylori) was more frequent in CU+ than CU-. Inverse correlations occurred between anti-T. gondii IgG and IL-2, and anti-Anisakis IgE and IFN-γ; positive correlations with anti-H. pylori IgG and IL-17A, and anti-EBV IgG and IL-6. T. gondii infection is associated with anti-A. simplex IgE regardless of CU. H. pylori infection is linked to CU independently of A. simplex sensitization. Studied coinfections modulate immune responses and alter cytokine profiles underscoring complex immunoregulatory mechanisms of Anisakis allergy.

卫生学假说认为,通过粪口途径或受污染的食物获得的感染,如弓形虫,可能会预防ige介导的过敏性疾病。Epstein-Barr病毒(EBV)与特应性反应呈负相关,而单根异尖线虫和幽门螺杆菌分别与急性和慢性荨麻疹相关。本研究旨在探讨共感染状态对异烟病相关表型的影响。根据异尖线虫致敏状态和临床表型对112名受试者进行分类:25人患有胃变态反应性异尖线虫病(GAA), 64人患有慢性荨麻疹(CU),其中32人对单纯性异尖线虫[CU+]致敏,23人没有荨麻疹。测定血清抗单纯单胞杆菌的IgE和抗弓形虫、幽门螺杆菌和EBV的IgG,以评估暴露和合并感染模式。流式细胞术检测血清细胞因子IL-2、IL-4、IL-6、IL-10、TNF-α、IFN-γ、IL-17A、TGF-β水平。单纯单胞杆菌血清阳性(AK+)患者中弓形虫合并感染发生率最高(95.3%),而幽门螺杆菌合并感染发生率在CU患者中较高(55.9%)。所有CU+患者均出现幽门螺杆菌合并感染和单纯单胞杆菌/幽门螺杆菌三重合并感染。刚/ H。幽门螺旋杆菌)在CU+中比CU-中更常见。抗- t。弓形虫IgG和IL-2,抗异尖线虫IgE和IFN-γ;与反h正相关。幽门螺杆菌IgG和IL-17A,抗ebv IgG和IL-6。弓形虫感染与抗a抗体有关。单纯IgE与CU无关。幽门螺杆菌感染与单纯单胞杆菌致敏无关。研究共感染调节免疫反应和改变细胞因子谱,强调异尖线虫过敏的复杂免疫调节机制。
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引用次数: 0
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Microbial pathogenesis
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