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Factors underlying the long-term efficacy of faecal microbiota transplantation for patients with irritable bowel syndrome. 粪便微生物群移植对肠易激综合征患者的长期疗效的基础因素。
IF 2.6 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-06-04 DOI: 10.1016/j.micinf.2024.105372
Magdy El-Salhy, Odd Helge Gilja, Jan Gunnar Hatlebakk

The long-term effects of the transplant dose, its administration route and repeated faecal microbiota transplantation (FMT) on the outcomes of FMT for patients with irritable bowel syndrome (IBS) are unknown. This study included 171 patients (125 females and 46 males): 90 g of donor feces was administered into the large intestine (LI) in 58, into the small intestine (SI) in 57, and into the SI twice (repeated SI) in 56. The patients provided a fecal sample and completed five questionnaires at the baseline and at 2 years after FMT. Fecal bacteria and the dysbiosis index were analyzed using 16S rRNA gene PCR DNA amplification/probe. The response rates at 2 years after FMT were 47.2%, 80.9%, and 76.6% in the LI, SI, and repeated-SI groups, respectively. The response rate was significantly higher in the SI and repeated SI groups than in the LI group. IBS symptoms at 2 years after FMT were less severe in the SI and repeated-SI groups than in the LI group. Fluorescent signals of several bacteria were significantly correlated with IBS symptoms and fatigue after FMT. No long-term adverse events were observed. In conclusion, administering the transplant to the SI increased the long-term response rate and reduced IBS symptom severity compared with administering it to the LI, and led to the long-term colonization of beneficial bacteria. There was no long-term difference between one and two FMT procedures (www.clinicaltrials.gov: NCT04236843).

移植剂量、给药途径和重复粪便微生物群移植(FMT)对肠易激综合征(IBS)患者治疗效果的长期影响尚不清楚。这项研究包括 171 名患者(125 名女性和 46 名男性):58名患者的大肠(LI)、57名患者的小肠(SI)和56名患者的两次小肠(SI)(重复SI)分别接受了90克的供体粪便。患者提供了粪便样本,并在 FMT 基线和 2 年后填写了 5 份问卷。采用 16S rRNA 基因 PCR DNA 扩增/探针分析粪便细菌和菌群失调指数。FMT治疗后2年,LI组、SI组和重复SI组的应答率分别为47.2%、80.9%和76.6%。SI组和重复SI组的应答率明显高于LI组。FMT治疗后2年,SI组和重复SI组的肠易激综合征症状轻于LI组。几种细菌的荧光信号与 FMT 后的肠易激综合征症状和疲劳明显相关。未观察到长期不良反应。总之,与给肠易激综合征患者施用移植疗法相比,给肠易激综合征患者施用移植疗法可提高长期反应率,减轻肠易激综合征症状的严重程度,并使有益细菌长期定植。一次和两次FMT手术之间没有长期差异。(www.clinicaltrials.gov: NCT04236843)。
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引用次数: 0
Extracellular vesicles in the pathogenesis of Campylobacter jejuni. 空肠弯曲杆菌致病过程中的胞外囊泡。
IF 5.8 4区 医学 Q1 Immunology and Microbiology Pub Date : 2024-06-01 DOI: 10.2139/ssrn.4748530
Jeanne Malet-Villemagne, J. Vidić
Bacteria in genus Campylobacter are the leading cause of foodborne infections worldwide. Here we describe the roles of extracellular vesicles in the pathogenesis of these bacteria and current knowledge of vesicle biogenesis. We also discuss the advantages of this alternative secretion pathway for bacterial virulence.
弯曲杆菌属细菌是全球食源性感染的主要病因。在此,我们介绍了胞外囊泡在这些细菌致病过程中的作用以及目前对囊泡生物发生的了解。我们还讨论了这种替代分泌途径在细菌毒力方面的优势。
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引用次数: 0
Leishmania donovani modulates host miRNAs regulating cholesterol biosynthesis for its survival 唐氏利什曼原虫调节宿主的 miRNA,调控胆固醇的生物合成,以促进其生存
IF 5.8 4区 医学 Q1 Immunology and Microbiology Pub Date : 2024-06-01 DOI: 10.1016/j.micinf.2024.105379
Shams Tabrez, Sajjadul Kadir Akand, Rahat Ali, Irshad Husain Naqvi, Neha Soleja, Mohd Mohsin, Mohammad Z. Ahmed, Mohammed Saleem, Suhel Parvez, Yusuf Akhter, Abdur Rub
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引用次数: 0
Lung infection with classical Klebsiella pneumoniae strains establishes robust macrophage-dependent protection against heterologous reinfection. 经典肺炎克雷伯氏菌菌株的肺部感染可建立对异源再感染的强大巨噬细胞依赖性保护。
IF 2.6 4区 医学 Q1 Immunology and Microbiology Pub Date : 2024-05-28 DOI: 10.1016/j.micinf.2024.105369
Joseph J Mackel, Casey L G Mick, Emily Guo, David A Rosen

At present, there is no approved vaccine for prevention of infection by the opportunistic bacterium Klebsiella pneumoniae (Kp); success in treating these infections is increasingly challenged by the spread of antibiotic resistance. Preclinical investigation of adaptive immunity elicited by lung infection with live classical Kp may reveal host mechanisms of protection against this pathogen. Here, we utilize multiple virulent classical Kp strains to demonstrate that following lung infection, surviving wild-type mice develop protective immunity against both homologous and heterologous (heterotypic) reinfection. For Kp strains with low capacity to disseminate from the lung, this immunity is B-cell-independent. We further demonstrate that this immune protection is also effective against subsequent challenge with hypervirulent Kp if the strains share the same capsule type. Systemic inoculation fails to elicit the same protective effect as lung inoculation, revealing a lung-specific immune effector function is responsible for this protection. We therefore utilized clodronate-loaded liposomes to substantially deplete both alveolar macrophages and lung interstitial macrophages, finding that simultaneous depletion of both subsets entirely ablates protection. These findings indicate that following initial lung infection with Kp, lung macrophages mediate protection against ensuing Kp challenge.

目前还没有获准用于预防机会性肺炎克雷伯氏菌(Kp)感染的疫苗;由于抗生素耐药性的蔓延,治疗此类感染的成功率日益受到挑战。对活体经典 Kp 引起的肺部感染所产生的适应性免疫进行临床前研究,可能会揭示宿主对这种病原体的保护机制。在这里,我们利用多种毒性经典 Kp 菌株证明,肺部感染后,存活的野生型小鼠会对同源和异源(异型)再感染产生保护性免疫。对于从肺部扩散能力较低的 Kp 菌株,这种免疫不依赖于 B 细胞。我们进一步证明,如果菌株的胶囊类型相同,这种免疫保护也能有效抵御高病毒性 Kp 的后续挑战。全身接种无法引起与肺部接种相同的保护效果,这表明肺部特异性免疫效应器功能是这种保护的原因。因此,我们利用负载氯膦酸脂质体来大量消耗肺泡巨噬细胞和肺间质巨噬细胞,结果发现同时消耗这两个亚群会完全削弱保护作用。这些研究结果表明,在肺部初次感染 Kp 后,肺巨噬细胞介导了对随后 Kp 挑战的保护。
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引用次数: 0
Characterization of novel HIV fusion-inhibitory lipopeptides with the M-T hook structure. 具有 M-T 钩结构的新型 HIV 融合抑制脂肽的特征。
IF 5.8 4区 医学 Q1 Immunology and Microbiology Pub Date : 2024-05-21 DOI: 10.1016/j.micinf.2024.105366
Xiuzhu Geng, Xiaohui Ding, Yuanmei Zhu, Huihui Chong, Yuxian He

Combination antiretroviral therapy (cART) has significantly improved the survival of HIV-infected individuals, but long-term treatment can cause side-effects and drug resistance; thus, the development of new antivirals is of importance. We previously identified an M-T hook structure and accordingly designed short-peptide fusion inhibitor 2P23, which mainly targets the gp41 pocket site and displays potent, broad-spectrum anti-HIV activity. In this study, we continuingly characterized the amino acid sequences of peptide and lipopeptide-based inhibitors containing the M-T hook residues. Among a group of lipopeptides, stearic acid (C18)-modified LP-25 and LP-29 exhibited greatly improved inhibitions against divergent HIV-1 subtypes and drug-resistant mutants. LP-25 and LP-29 were evaluated in rhesus macaques, and the ex vivo inhibition data demonstrated their potent, long-lasting in vivo anti-HIV activity, with LP-25 much better than LP-29. Both the lipopeptides displayed high α-helicity, thermostability and binding ability to a target-mimic peptide, and they were metabolically stable when treated with high temperature, proteolytic enzymes, human or monkey sera and human liver microsomes. Therefore, our studies have provided critical information for understanding the structure-activity relationship of HIV fusion inhibitors with the M-T hook structure and offered novel candidates for drug development.

联合抗逆转录病毒疗法(cART)大大提高了艾滋病毒感染者的生存率,但长期治疗会产生副作用和耐药性;因此,开发新的抗病毒药物非常重要。我们之前确定了 M-T 钩结构,并据此设计了短肽融合抑制剂 2P23,它主要针对 gp41 口袋位点,具有强效、广谱的抗 HIV 活性。在这项研究中,我们继续对含有 M-T 钩残基的肽类和脂肽类抑制剂的氨基酸序列进行了表征。在一组脂肽中,经硬脂酸(C18)修饰的 LP-25 和 LP-29 对不同 HIV-1 亚型和耐药突变体的抑制作用大大提高。在猕猴体内对 LP-25 和 LP-29 进行了评估,其体内外抑制数据表明,它们具有强效、持久的体内抗 HIV 活性,其中 LP-25 的效果比 LP-29 更好。这两种脂肽都显示出很高的α-螺旋度、热稳定性和与目标模拟肽的结合能力,而且在高温、蛋白水解酶、人或猴血清和人肝微粒体的作用下,它们的代谢都很稳定。因此,我们的研究为理解具有 M-T 钩结构的 HIV 融合抑制剂的结构-活性关系提供了关键信息,并为药物开发提供了新的候选物。
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引用次数: 0
Efficacy of 233 nm LED far UV-C-radiation against clinically relevant bacterial strains in the phase 2/ step 2 in vitro test on basis of EN 14561 and on an epidermis cell model 根据 EN 14561 和表皮细胞模型,在第二阶段/第二步体外试验中,233 纳米 LED 远紫外线-C 辐射对临床相关细菌菌株的功效。
IF 5.8 4区 医学 Q1 Immunology and Microbiology Pub Date : 2024-05-01 DOI: 10.1016/j.micinf.2024.105320
Claudia Sicher , Nevin Opitz , Pia Elen Becker , Neysha Lobo Ploch , Johannes Schleusener , Michael Kneissl , Axel Kramer , Paula Zwicker

Introduction

Healthcare-acquired infections and overuse of antibiotics are a common problem. Rising emergence of antibiotic and antiseptic resistances requires new methods of microbial decontamination or decolonization as the use of far-UV-C radiation.

Methods

The microbicidal efficacy of UV-C radiation (222 nm, 233 nm, 254 nm) was determined in a quantitative carrier test and on 3D-epidermis models against Staphylococcus (S.) aureus, S. epidermidis, S. haemolyticus, S. lugdunensis, Klebsiella pneumoniae, and Pseudomonas aeruginosa. To mimic realistic conditions, sodium chloride solution, mucin, albumin, artificial saliva, artificial wound exudate and artificial sweat were used.

Results

In sodium chloride solution, irradiation with a dose of 40 mJ/cm2 (233 nm) was sufficient to achieve 5 lg reduction independent of bacteria genus or species. In artificial sweat, albumin and artificial wound exudate, a reduction >3 lg was reached for most of the bacteria. Mucin and artificial saliva decreased the reduction to <2 lg. On 3D epidermis models, reduction was lower than in the carrier test.

Conclusion

UV-C radiation at 233 nm was proven to be efficient in bacteria inactivation independent of genus or species thus being a promising candidate for clinical use in the presence of humans and on skin/mucosa.

导言:医源性感染和过度使用抗生素是一个常见问题。抗生素和防腐剂耐药性的不断增加需要新的微生物净化或去殖民化方法,如使用远紫外线-C 辐射:在定量载体试验和三维表皮模型中测定了紫外线-C 辐射(222 nm、233 nm、254 nm)对金黄色葡萄球菌、表皮葡萄球菌、溶血性葡萄球菌、卢格登氏菌、肺炎克雷伯氏菌和绿脓杆菌的杀菌效果。为了模拟现实条件,使用了氯化钠溶液粘蛋白、白蛋白、人工唾液、人工伤口渗出液和人工汗液:在氯化钠溶液中,40 mJ/cm2 (233 nm)的照射剂量足以减少 5 lg 的细菌,而与细菌的属或种无关。在人工汗液、白蛋白和人工伤口渗出液中,大多数细菌的减少量大于 3 lg。粘液蛋白和人工唾液则将细菌减少量降至结论水平:事实证明,波长为 233 纳米的紫外线-C 辐射能有效灭活不同属种的细菌,因此有望在人体和皮肤/粘膜上应用于临床。
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引用次数: 0
Candida albicans increases the aerobic glycolysis and activates MAPK–dependent inflammatory response of liver sinusoidal endothelial cells 白色念珠菌增加肝窦内皮细胞的有氧糖酵解并激活 MAPK 依赖性炎症反应
IF 5.8 4区 医学 Q1 Immunology and Microbiology Pub Date : 2024-05-01 DOI: 10.1016/j.micinf.2024.105305
Leire Aparicio-Fernandez , Aitziber Antoran , Maialen Areitio , Oier Rodriguez-Erenaga , Leire Martin-Souto , Idoia Buldain , Joana Márquez , Aitor Benedicto , Beatriz Arteta , Aize Pellon , David L. Moyes , Aitor Rementeria , Andoni Ramirez-Garcia

The liver, and more specifically, the liver sinusoidal endothelial cells, constitute the beginning of one of the most important responses for the elimination of hematogenously disseminated Candida albicans. Therefore, we aimed to study the mechanisms involved in the interaction between these cells and C. albicans. Transcriptomics-based analysis showed an increase in the expression of genes related to the immune response (including receptors, cytokines, and adhesion molecules), as well as to aerobic glycolysis. Further in vitro analyses showed that IL-6 production in response to C. albicans is controlled by MyD88- and SYK-pathways, suggesting an involvement of Toll-like and C-type lectin receptors and the subsequent activation of the MAP-kinases and c-Fos/AP-1 transcription factor. In addition, liver sinusoidal endothelial cells undergo metabolic reprogramming towards aerobic glycolysis induced by C. albicans, as confirmed by the increased Extracellular Acidification Rate and the overexpression of enolase (Eno2), hexonikase (Hk2) and glucose transporter 1 (Slc2a1). In conclusion, these results indicate that the hepatic endothelium responds to C. albicans by increasing aerobic glycolysis and promoting an inflammatory environment.

肝脏,更具体地说,肝窦内皮细胞,是消除血源性传播的白色念珠菌的最重要反应之一的起始点。因此,我们旨在研究这些细胞与白念珠菌之间的相互作用机制。基于转录组学的分析表明,与免疫反应(包括受体、细胞因子和粘附分子)以及有氧糖酵解相关的基因表达量有所增加。进一步的体外分析表明,白僵菌反应产生的 IL-6 受 MyD88 和 Syk 途径控制,这表明 Toll 样受体和 C 型凝集素受体参与其中,随后激活了 MAP 激酶和 c-Fos/AP-1 转录因子。此外,肝窦状内皮细胞在白璧酵母的诱导下进行了代谢重编程,转向有氧糖酵解,细胞外酸化率的增加和烯醇化酶(Eno2)、己酮酶(Hk2)、葡萄糖转运体 1(Slc2a1)的过表达证实了这一点。总之,这些结果表明,肝内皮细胞通过增加有氧糖酵解和促进炎症环境来应对白僵菌。
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引用次数: 0
Can Lacticaseibacillus rhamnosus CRL1505 postbiotic improve emergency myelopoiesis in immunocompromised mice? 鼠李糖乳杆菌 CRL1505 后益生菌能改善免疫受损小鼠的紧急骨髓造血功能吗?
IF 5.8 4区 医学 Q1 Immunology and Microbiology Pub Date : 2024-05-01 DOI: 10.1016/j.micinf.2024.105311
Andrés Gramajo López , Brenda Vasile , Yanina Kolling , Maximiliano Ivir , Florencia Gutiérrez , Susana Alvarez , Susana Salva

We evaluated whether viable and non-viable Lacticaseibacillus rhamnosus CRL1505 (Lr05V or Lr05NV, respectively) was able to improve emergency myelopoiesis induced by Streptococcus pneumoniae (Sp) infection.

Adult Swiss-mice were orally treated with Lr05V or Lr05NV during five consecutive days. The Lr05V and Lr05NV groups and untreated control group received an intraperitoneal dose of cyclophosphamide (Cy-150 mg/kg). Then, the mice were nasally challenged with Sp (107 UFC/mice) on day 3 post-Cy injection. After the pneumococcal challenge, the innate and myelopoietic responses were evaluated.

The control group showed a high susceptibility to pneumococcal infection, an impaired innate immune response and a decrease of hematopoietic stem cells (HSCs: LinSca-1+c-Kit+), and myeloid multipotent precursors (MMPs: Gr-1+Ly6G+Ly6C) in bone marrow (BM). However, lactobacilli treatments were able to significantly increase blood neutrophils and peroxidase-positive cells, while improving cytokine production and phagocytic activity of alveolar macrophages. This, in turn, led to an early Sp lung clearance compared to the control group. Furthermore, Lr05V was more effective than Lr05NV to increase growth factors in BM, which allowed an early HSCs and MMPs recovery with respect to the control group.

Both Lr05V and Lr05NV were able to improve BM emergency myelopiesis and protection against respiratory pathogens in mice undergoing chemotherapy.

我们评估了有活力和无活力的鼠李糖乳杆菌 CRL1505(分别为 Lr05V 或 Lr05NV)是否能改善肺炎链球菌(Sp)感染诱导的紧急骨髓造血。成年瑞士小鼠连续五天口服 Lr05V 或 Lr05NV。Lr05V 组、Lr05NV 组和未处理对照组腹腔注射环磷酰胺(Cy-150 mg/kg)。然后,在注射 Cy 后的第 3 天,用 Sp(107 UFC/只小鼠)对小鼠进行鼻腔挑战。肺炎球菌挑战后,对先天性反应和骨髓造血反应进行了评估。对照组对肺炎球菌感染表现出高度易感性,先天性免疫反应受损,骨髓(BM)中的造血干细胞(HSCs:Lin-Sca-1+c-Kit+)和髓系多能前体(MMPs:Gr-1+Ly6G+Ly6C-)减少。然而,乳酸菌能显著增加血液中的中性粒细胞和过氧化物酶阳性细胞,同时改善细胞因子的产生和肺泡巨噬细胞的吞噬活性。与对照组相比,这反过来又导致了 Sp 肺早期清除。此外,与对照组相比,Lr05V 比 Lr05NV 能更有效地增加 BM 中的生长因子,从而使造血干细胞和 MMPs 早日恢复。Lr05V和Lr05NV都能改善化疗小鼠的骨髓细胞紧急凋亡和对呼吸道病原体的保护。
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引用次数: 0
Virome survey of the bat, Rhinolophus affinis, in Hainan Province, China 中国海南省蝙蝠(Rhinolophus affinis)病毒组调查。
IF 5.8 4区 医学 Q1 Immunology and Microbiology Pub Date : 2024-05-01 DOI: 10.1016/j.micinf.2024.105331
Zihan Li , Chuanning Tang , Youyou Li , Yun Zhang , Gaoyu Wang , Ruoyan Peng , Yi Huang , Xiaoyuan Hu , Henan Xin , Xuefang Cao , Lingyu Shen , Tonglei Guo , Yijun He , Boxuan Fen , Juanjuan Huang , Jian guo Liang , Xiuji Cui , Lina Niu , Jian Yang , Fan Yang , Jiang Du

Bats are important mammal reservoirs of zoonotic pathogens. However, due to research limitations involving species, locations, pathogens, or sample types, the full diversity of viruses in bats remains to be discovered. We used next-generation sequencing technology to characterize the mammalian virome and analyze the phylogenetic evolution and diversity of mammalian viruses carried by bats from Haikou City and Tunchang County in Hainan Province, China. We collected 200 pharyngeal swab and anal swab samples from Rhinolophus affinis, combining them into nine pools based on the sample type and collection location. We subjected the samples to next-generation sequencing and conducted bioinformatics analysis. All samples were screened via specific PCR and phylogenetic analysis. The diverse viral reads, closely related to mammals, were assigned into 17 viral families. We discovered many novel bat viruses and identified some closely related to known human/animal pathogens. In the current study, 6 complete genomes and 2 partial genomic sequences of 6 viral families and 8 viral genera have been amplified, among which 5 strains are suggested to be new virus species. These included coronavirus, pestivirus, bastrovirus, bocavirus, papillomavirus, parvovirus, and paramyxovirus. The primary finding is that a SADS-related CoV and a HoBi-like pestivirus identified in R. affinis in Hainan Province could be pathogenic to livestock. This study expands our understanding of bats as a virus reservoir, providing a basis for further research on the transmission of viruses from bats to humans.

蝙蝠是人畜共患病原体的重要哺乳动物贮藏地。然而,由于涉及物种、地点、病原体或样本类型的研究限制,蝙蝠体内病毒的全部多样性仍有待发现。我们利用新一代测序技术描述了哺乳动物病毒组的特征,并分析了中国海南省海口市和屯昌县蝙蝠携带的哺乳动物病毒的系统进化和多样性。我们采集了200份鼻蝠的咽拭子和肛拭子样本,根据样本类型和采集地点分成9个样本库。我们对样本进行了新一代测序,并进行了生物信息学分析。我们通过特异性 PCR 和系统进化分析对所有样本进行了筛选。与哺乳动物密切相关的各种病毒读数被归入 17 个病毒科。我们发现了许多新型蝙蝠病毒,并确定了一些与已知人类/动物病原体密切相关的病毒。本次研究共扩增了 6 个病毒科和 8 个病毒属的 6 个完整基因组和 2 个部分基因组序列,其中 5 个毒株被认为是新病毒种。这些病毒包括冠状病毒、虫媒病毒、韧皮部病毒、球形病毒、乳头瘤病毒、副粘病毒和副粘病毒。研究的主要发现是,在海南省发现的一种与 SADS 相关的 CoV 和一种类似 HoBi 的虫媒病毒可能对家畜具有致病性。这项研究拓展了我们对蝙蝠作为病毒库的认识,为进一步研究病毒从蝙蝠向人类的传播提供了基础。
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引用次数: 0
Blocking pathogenic Leptospira invasion with aptamer molecules targeting outer membrane LipL32 protein 以外膜 LipL32 蛋白为靶标的 Aptamer 分子阻断病原性钩端螺旋体的入侵
IF 5.8 4区 医学 Q1 Immunology and Microbiology Pub Date : 2024-05-01 DOI: 10.1016/j.micinf.2024.105299
Shen-Hsing Hsu , Huang-Yu Yang , Chia-Chen Chang , Shou-Kuan Tsai , Chien Li , Ming-Yang Chang , Yi-Ching Ko , Li-Fang Chou , Chung-Ying Tsai , Ya-Chung Tian , Chih-Wei Yang

This study aimed to develop aptamers targeting LipL32, a most abundant lipoprotein in pathogenic Leptospira, to hinder bacterial invasion. The objectives were to identify high-affinity aptamers through SELEX and evaluate their specificity and inhibitory effects. SELEX was employed to generate LipL32 aptamers (L32APs) over 15 rounds of selection. L32APs' binding affinity and specificity for pathogenic Leptospira were assessed. Their ability to inhibit LipL32-ECM interaction and Leptospira invasion was investigated. Animal studies were conducted to evaluate the impact of L32AP treatment on survival rates, Leptospira colonization, and kidney damage. Three L32APs with strong binding affinity were identified. They selectively detected pathogenic Leptospira, sparing non-pathogenic strains. L32APs inhibited LipL32-ECM interaction and Leptospira invasion. In animal studies, L32AP administration significantly improved survival rates, reduced Leptospira colonies, and mitigated kidney damage compared to infection alone. This pioneering research developed functional aptamers targeting pathogenic Leptospira. The identified L32APs exhibited high affinity, pathogen selectivity, and inhibition of invasion and ECM interaction. L32AP treatment showed promising results, enhancing survival rates and reducing Leptospira colonization and kidney damage. These findings demonstrate the potential of aptamers to impede pathogenic Leptospira invasion and aid in recovery from Leptospira-induced kidney injury (190 words).

本研究旨在开发针对病原钩端螺旋体中最丰富的脂蛋白 LipL32 的适配体,以阻止细菌入侵。目的是通过 SELEX 找出高亲和力的适配体,并评估其特异性和抑制作用。通过15轮筛选,SELEX产生了LipL32适配体(L32APs)。评估了 L32APs 与致病性钩端螺旋体的结合亲和力和特异性。研究了它们抑制 LipL32-ECM 相互作用和钩端螺旋体入侵的能力。通过动物实验评估了 L32AP 治疗对存活率、钩端螺旋体定植和肾损伤的影响。研究发现了三种具有强结合亲和力的 L32AP。它们能选择性地检测致病性钩端螺旋体,而不检测非致病性菌株。L32APs 可抑制 LipL32-ECM 相互作用和钩端螺旋体入侵。在动物实验中,与单纯感染相比,服用 L32AP 能显著提高存活率,减少钩端螺旋体菌落,减轻肾脏损伤。这项开创性研究开发出了针对致病性钩端螺旋体的功能性适配体。鉴定出的 L32APs 具有高亲和力、病原体选择性、抑制侵袭和 ECM 相互作用。L32AP 治疗效果良好,提高了存活率,减少了钩端螺旋体定植和肾损伤。这些研究结果表明了适配体在阻碍致病性钩端螺旋体入侵和帮助钩端螺旋体引起的肾损伤恢复方面的潜力。(190字)
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引用次数: 0
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