Bacterial Infection

细菌感染
  • 文章类型: Journal Article
    由致病菌引起的传染病在全球范围内的传播引起了公众的极大关注,以及敏感的方法,选择性,和细菌的轻松诊断可以有效地防止感染的恶化和进一步传播。纳米酶的出现扩大了诊断细菌感染的替代方案的范围。与天然酶相比,纳米酶表现出相同的酶学特性,但提供更大的经济效率,增强耐用性,和可调尺寸。介绍了细菌感染早期诊断和常规诊断方法的重要性。随后,审查阐明了定义,属性,和纳米酶的催化机理。最终,探索了纳米酶在细菌检测中的详细应用,强调它们作为生物传感器的利用,可以加速和高度敏感地识别细菌感染,并反映基于纳米酶的细菌检测作为即时检测(POCT)工具的潜力。本综述的结论简要介绍了该领域的障碍和未来前景。
    The global spread of infectious diseases caused by pathogenic bacteria significantly poses public health concerns, and methods for sensitive, selective, and facile diagnosis of bacteria can efficiently prevent deterioration and further spreading of the infections. The advent of nanozymes has broadened the spectrum of alternatives for diagnosing bacterial infections. Compared to natural enzymes, nanozymes exhibit the same enzymatic characteristics but offer greater economic efficiency, enhanced durability, and adjustable dimensions. The importance of early diagnosis of bacterial infection and conventional diagnostic approaches is introduced. Subsequently, the review elucidates the definition, properties, and catalytic mechanism of nanozymes. Eventually, the detailed application of nanozymes in detecting bacteria is explored, highlighting their utilization as biosensors that allow for accelerated and highly sensitive identification of bacterial infections and reflecting on the potential of nanozyme-based bacterial detection as a point-of-care testing (POCT) tool. A brief summary of obstacles and future perspectives in this field is presented at the conclusion of this review.
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  • 文章类型: Journal Article
    单核细胞增生李斯特菌是食源性细胞内细菌模型病原体。针对李斯特菌的保护性免疫取决于有效的CD8+T细胞反应,但是在小鼠中很少有T细胞表位被认为是李斯特菌病的常见动物感染模型。为了鉴定表位,我们通过基于质谱的免疫肽筛选了感染小鼠脾脏中存在的李斯特菌免疫肽。我们绘制了在MHCI类分子上呈递的6000多个小鼠自身肽,包括来自12种不同细菌蛋白的12种高度自信的李斯特菌肽。进一步测试了具有确认片段谱的细菌免疫肽激活CD8+T细胞的潜力。从推定的细胞壁表面锚家族蛋白LMON_0576中揭示VTYNYINI作为一种新型的真正的肽表位。该表位在初免加强模型中显示出高生物学效力,并且可以用作研究工具以探测李斯特菌感染的小鼠模型中的CD8+T细胞应答。一起,我们的结果证明了免疫肽用于细菌抗原鉴定的能力。
    Listeria monocytogenes is a foodborne intracellular bacterial model pathogen. Protective immunity against Listeria depends on an effective CD8+ T cell response, but very few T cell epitopes are known in mice as a common animal infection model for listeriosis. To identify epitopes we screened for Listeria immunopeptides presented in the spleen of infected mice by mass spectrometry-based immunopeptidomics. We mapped more than 6,000 mouse self-peptides presented on MHC Class I molecules, including 12 high confident Listeria peptides from 12 different bacterial proteins. Bacterial immunopeptides with confirmed fragmentation spectra were further tested for their potential to activate CD8+ T cells, revealing VTYNYINI from the putative cell wall surface anchor family protein LMON_0576 as a novel bona fide peptide epitope. The epitope showed high biological potency in a prime boost model and can be used as a research tool to probe CD8+ T cell responses in mouse models of Listeria infection. Together, our results demonstrate the power of immunopeptidomics for bacterial antigen identification.
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  • 文章类型: Journal Article
    背景:棕色脂肪组织(BAT)燃烧脂质和葡萄糖以产生热量。通过这个非颤抖的产热过程,BAT在寒冷环境中的体温调节中起着关键作用,但其对免疫引起的发热的作用尚不清楚。
    方法:男性APOE*3-莱顿。CETP小鼠,一个完善的人样脂蛋白代谢模型,和野生型小鼠腹膜内注射肠沙门氏菌(S.tm)。能量消耗和衬底利用率,血浆脂质水平,脂肪组织摄取脂肪酸,并检查了脂肪组织中的脂质含量和产热标志物。
    结果:S.tm感染导致一系列特征性症状,包括体温升高和体重下降。感染后72小时,全身能量消耗显着降低,但是脂肪氧化增加,并伴有血浆甘油三酯(TG)水平的大幅降低,如APOE*3-Leiden所示。CETP小鼠。S.tm感染强烈增加了BAT对富含TG的脂蛋白(TRLs)中脂肪酸的摄取,与感染小鼠的体温呈正相关。对野生型或APOE*3-莱顿的BAT进行组织学检查。CETP小鼠,观察到酪氨酸羟化酶水平升高,指示受刺激的交感神经活动。此外,基因表达谱与更多的肾上腺素能刺激一致,而脂质含量降低。此外,观察到白色脂肪组织褐变,由TG衍生的脂肪酸摄取适度增加证明,多房细胞的存在,和诱导UCP-1表达。
    结论:我们建议BAT,或一般的产热脂肪组织,涉及在侵入性细菌感染后维持升高的体温。
    BACKGROUND: Brown adipose tissue (BAT) combusts lipids and glucose to generate heat. Via this process of non-shivering thermogenesis, BAT plays a pivotal role in thermoregulation in cold environments, but its contribution to immune-induced fever is less clear.
    METHODS: Male APOE*3-Leiden.CETP mice, a well-established model for human-like lipoprotein metabolism, and wildtype mice were given an intraperitoneal injection of Salmonella enterica serovar Typhimurium (S.tm). Energy expenditure and substrate utilization, plasma lipid levels, fatty acid uptake by adipose tissues, and lipid content and thermogenic markers in adipose tissues were examined.
    RESULTS: S.tm infection led to a set of characteristic symptoms, including elevated body temperature and decreased body weight. Whole-body energy expenditure was significantly decreased 72 hours post-infection, but fat oxidation was increased and accompanied by a substantial reduction in plasma triglyceride (TG) levels as demonstrated in APOE*3-Leiden.CETP mice. S.tm infection strongly increased uptake of fatty acids from TG-rich lipoproteins (TRLs) by BAT, which showed a positive correlation with body temperature in infected mice. Upon histological examination of BAT from wildtype or APOE*3-Leiden.CETP mice, elevated levels of tyrosine hydroxylase were observed, indicative of stimulated sympathetic activity. In addition, the gene expression profile was consistent with more adrenergic stimulation, while lipid content was reduced. Furthermore, browning of white adipose tissue was observed, evidenced by a modest increase in TG-derived fatty acid uptake, the presence of multilocular cells, and induction of UCP-1 expression.
    CONCLUSIONS: We proposed that BAT, or thermogenic adipose tissue in general, is involved in the maintenance of elevated body temperature upon invasive bacterial infection.
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  • 文章类型: Journal Article
    伤口易于感染,这可能对患者的生命是致命的。抗生素的使用对于控制伤口中的细菌感染至关重要,但是长期使用高剂量的抗生素可能会导致细菌耐药性,甚至产生超级细菌。因此,制定针对性的抗菌治疗策略和减少抗生素的使用是当务之急.在这项研究中,通过Zn2+的自组装合成了一种用于治疗抑菌感染的多功能纳米药物递送系统(Cef-rhEGF@ZIF-8@ConA),头孢拉定(Cef)和重组人表皮生长因子(rhEGF),然后与伴刀豆球蛋白(ConA)缀合,其经历pH响应性降解以释放药物。首先,ConA能与细菌特异性结合,抑制Zn2+离子的快速释放,从而达到长效抗菌效果。Cef通过抑制细菌膜蛋白的合成发挥其抗菌作用。最后,从Zn-金属-有机骨架(MOF)释放的Zn2离子通过增强细菌细胞膜的渗透性而表现出抑菌特性。此外,rhEGF上调血管生成相关基因,从而促进血管生成,上皮再生和伤口愈合过程。结果表明,Cef-rhEGF@ZIF-8@ConA具有良好的生物相容性,对金黄色葡萄球菌和大肠杆菌的抗菌效果分别为99.61%和99.75%,分别。这些纳米材料可以抑制炎症细胞因子的释放,促进抗炎细胞因子的释放,同时还刺激成纤维细胞的增殖以促进伤口愈合。一起来看,Cef-rhEGF@ZIF-8@ConA纳米系统是抑菌感染和伤口愈合的临床治疗的优秀候选者。
    Wounds are prone to infection which may be fatal to the life of the patient. The use of antibiotics is essential for managing bacterial infections in wounds, but the long-term use of high doses of antibiotics may lead to bacterial drug resistance and even to creation of superbacteria. Therefore, the development of targeted antimicrobial treatment strategies and the reduction in antibiotic usage are of utmost urgency. In this study, a multifunctional nanodrug delivery system (Cef-rhEGF@ZIF-8@ConA) for the treatment of bacteriostatic infection was synthesized through self-assembly of Zn2+, cefradine (Cef) and recombinant human epidermal growth factor (rhEGF), then conjugated with concanavalin (ConA), which undergoes pH-responsive degradation to release the drugs. First, ConA can specifically combine with bacteria and inhibit the rapid release of Zn2+ ions, thus achieving a long-acting antibacterial effect. Cef exerts its antibacterial effect by inhibiting the synthesis of bacterial membrane proteins. Finally, Zn2+ ions released from the Zn-metal-organic framework (MOF) demonstrate bacteriostatic properties by enhancing the permeability of the bacterial cell membrane. Furthermore, rhEGF upregulates angiogenesis-associated genes, thereby promoting angiogenesis, re-epithelialization and wound healing processes. The results showed that Cef-rhEGF@ZIF-8@ConA has good biocompatibility, with antibacterial efficacy against Staphylococcus aureus and Escherichia coli of 99.61 % and 99.75 %, respectively. These nanomaterials can inhibit the release of inflammatory cytokines and promote the release of anti-inflammatory cytokines, while also stimulating the proliferation of fibroblasts to facilitate wound healing. Taken together, the Cef-rhEGF@ZIF-8@ConA nanosystem is an excellent candidate in clinical therapeutics for bacteriostatic infection and wound healing.
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  • 文章类型: Journal Article
    囊性纤维化(CF)患者容易发生威胁生命的肺部感染,并伴有多种难以根除的病原体,如洋葱伯克霍尔德菌(Bcc),流感嗜血杆菌,脓肿分枝杆菌(Mab),铜绿假单胞菌,和金黄色葡萄球菌。这些感染仍然是一个重要的问题,尽管近年来CF的治疗有了很大改善。此外,长期接触抗生素有利于多重耐药细菌的发展和传播;因此,替代策略的制定对于对抗抗菌素耐药性至关重要.在这种情况下,噬菌体疗法,即,噬菌体的使用,特别感染细菌的病毒,已经成为一种有前途的战略。在这次审查中,我们的目标是解决噬菌体疗法在多重耐药感染管理中的现状,从富有同情心的用例到正在进行的临床试验,以及这种方法在CF患者的特殊情况下所面临的挑战。
    Patients with cystic fibrosis (CF) are prone to developing life-threatening lung infections with a variety of pathogens that are difficult to eradicate, such as Burkholderia cepacia complex (Bcc), Hemophilus influenzae, Mycobacterium abscessus (Mab), Pseudomonas aeruginosa, and Staphylococcus aureus. These infections still remain an important issue, despite the therapy for CF having considerably improved in recent years. Moreover, prolonged exposure to antibiotics in combination favors the development and spread of multi-resistant bacteria; thus, the development of alternative strategies is crucial to counter antimicrobial resistance. In this context, phage therapy, i.e., the use of phages, viruses that specifically infect bacteria, has become a promising strategy. In this review, we aim to address the current status of phage therapy in the management of multidrug-resistant infections, from compassionate use cases to ongoing clinical trials, as well as the challenges this approach presents in the particular context of CF patients.
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  • 文章类型: Journal Article
    细菌的快速增殖和感染,尤其是多重耐药细菌,已经成为全球公共卫生的巨大威胁。重点关注抗生素滥用引起的"超级耐药菌"的出现,细菌性疾病的早期诊断不足和延误,开发新的技术和方法对细菌感染的早期针对性检测和治疗具有重要的研究意义。金属纳米颗粒基于其独特的物理和化学性质的特殊效果使得这种系统非常适合在体外和体内检测和治疗细菌感染。金属纳米粒子由于其抗菌谱广,也具有令人钦佩的临床应用前景,各种抗菌机制和优异的生物相容性。在这里,综述了金属纳米粒子在抗菌活性和细菌检测方面的作用机制的研究进展。选择代表性的成就来说明体外和体内应用的概念验证。基于这些观察,我们还简要讨论了金属纳米颗粒在细菌感染诊断和治疗中存在的问题和前景。
    The rapid proliferation and infection of bacteria, especially multidrug-resistant bacteria, have become a great threat to global public health. Focusing on the emergence of \"super drug-resistant bacteria\" caused by the abuse of antibiotics and the insufficient and delayed early diagnosis of bacterial diseases, it is of great research significance to develop new technologies and methods for early targeted detection and treatment of bacterial infection. The exceptional effects of metal nanoparticles based on their unique physical and chemical properties make such systems ideal for the detection and treatment of bacterial infection both in vitro and in vivo. Metal nanoparticles also have admirable clinical application prospects due to their broad antibacterial spectrum, various antibacterial mechanisms and excellent biocompatibility. Herein, we summarized the research progress concerning the mechanism of metal nanoparticles in terms of antibacterial activity together with the detection of bacterial. Representative achievements are selected to illustrate the proof-of-concept in vitro and in vivo applications. Based on these observations, we also give a brief discussion on the current problems and perspective outlook of metal nanoparticles in the diagnosis and treatment of bacterial infection.
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  • 文章类型: Journal Article
    鱼的皮肤粘液装有免疫和抗微生物肽,可提供针对入侵病原体的保护。已经在鱼类中研究了皮肤粘液,但是有关其在细菌感染中的免疫作用的信息很少。这项研究强调了默默无闻的河豚Takifuguobscurus的皮肤粘液中的蛋白质和肽,这些蛋白质和肽对嗜水气单胞菌的感染产生了定量变化。我们通过浸泡浴缸感染了鱼,内心,然后使用液相色谱-串联质谱(LC-MS/MS)分析比较各组中皮肤粘液中的蛋白质水平。基于串联质量标签(TMT)的定量显示,4896种蛋白质是优选定量的蛋白质(DQP),基于19,751种独特的肽。其中170个被耗尽(丰度降低),69个在浴处理(BT)与对照(C)组的比较中是丰富的。同样,与治疗组(T)和BT组相比,76个DQP被耗尽,70个丰富。Further,126DQP耗尽,与T组和C组相比,有34个是丰富的。我们报告的DQP主要是免疫学的,并且涉及独特的生物学功能和途径。我们报道的有趣的蛋白质,其中一些蛋白质首次出现在鱼类中,显示了鱼粘液的富含蛋白质的结构,它可以作为生物标志物,用于鱼类的细菌性疾病治疗,并最终暗示了鱼类对细菌性病原体产生抗性的方法。
    The skin mucus of fish is equipped with immunological and antimicrobial peptides that confer protection against invading pathogens. The skin mucus has been studied in fish however information regarding its immunological roles in bacterial infection is rare. This study highlighted the proteins and peptides in the skin mucus of Obscure puffer Takifugu obscurus that quantitatively altered against Aeromonas hydrophila infection. We infected the fish through bath immersion, intraperitonially, and treated with PBS (control) then compared the level of proteins in the skin mucus among the groups using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The Tandem Mass Tag (TMT) based quantification showed that 4896 proteins were Deferentially Quantified Proteins (DQPs), based on 19,751 unique peptides. Of which 170 were depleted (decreased in abundance) and 69 were abundant in comparison of Bath Treated (BT) vs Control (C) groups. Similarly, 76 DQPs were depleted and 70 were abundant in comparison of Treated (T) vs BT groups. Further, 126 DQPs were depleted, and 34 were abundant in comparison to T vs C groups. The DQPs we report were mostly immunological and were involved in unique biological functions and pathways. The interesting protein we report, where some of the proteins are for the first time in fish, shows the protein-rich structure of the mucus of fish, which may act as a biomarker to be targeted for bacterial disease therapy in fish and ultimately hint to the way of making resistance in fish against bacterial pathogens.
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  • 文章类型: Case Reports
    肾静脉血栓形成(RVT)在肾病综合征患者中并不少见。细菌感染引起的肾囊肿也很少见。在英语文献中,仅报道了一例RVT并发感染的肾囊肿。一名78岁的女性因发烧和昏昏欲睡的心态入院4天。腹部对比增强计算机断层扫描(CECT)显示3.7cm大小的不规则形状的外生性囊肿在左肾上极和左RVT中得到充分增强。囊液培养显示肺炎克雷伯菌。我们的患者接受了8周的抗生素和12周的抗凝剂的有效治疗。在12周的随访中,肾脏CECT显示囊肿减少,RVT几乎消失。值得考虑的是,细菌感染肾囊肿患者发生RVT的可能性。
    Renal vein thrombosis (RVT) is not an uncommon condition in patients occurring nephrotic syndrome. Renal cyst by bacterial infection is also rare. Only one case for RVT complicated with infected renal cyst is reported in the English literature. A 78-year-old female was admitted for fever and drowsy mentality for 4 days. Contrast-enhanced computed tomography (CECT) of the abdomen showed 3.7 cm sized irregular shaped exophytic cyst well enhanced in left kidney upper pole and the left RVT. The culture of cystic fluid revealed Klebsiella pneumoniae. Our patient was effectively treated with antibiotics for 8 weeks and anticoagulant for 12 weeks. At 12-week follow-up, CECT of the kidney showed decreased cyst and nearly disappeared RVT. The possibility of RVT in patients with renal cyst infection by bacteria warrants consideration.
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  • 文章类型: Journal Article
    生物体对病原体和其他外部威胁使用组成型或诱导型防御。宪法性防御一直在进行,而诱导防御在需要时被激活。这些策略都有成本和收益,这可能会影响响应病原体而进化的防御类型。此外,诱导防御通常由多个负反馈机制调节,防止过度激活的免疫反应。然而,目前还不清楚负反馈如何影响成本,好处,和诱导反应的进化。为了解决这个差距,我们建立了一个具有良好特征的果蝇免疫信号网络的机制模型,该模型包括三个独立的负反馈机制,代表了诱导反应的多级调节的普遍现象.我们证明,在随机的细菌接触下,当细菌接触很少或不确定时,诱导防御是有利的,而是取决于细菌的增殖率。我们的模型还预测,优化诱导反应的特定负调节因子取决于细菌增殖率,将负反馈机制与有利于诱导的因素联系起来。
    Organisms use constitutive or induced defenses against pathogens and other external threats. Constitutive defenses are constantly on, whereas induced defenses are activated when needed. Each of these strategies has costs and benefits, which can affect the type of defense that evolves in response to pathogens. In addition, induced defenses are usually regulated by multiple negative feedback mechanisms that prevent overactivation of the immune response. However, it is unclear how negative feedback affects the costs, benefits, and evolution of induced responses. To address this gap, we developed a mechanistic model of the well-characterized Drosophila melanogaster immune signaling network that includes three separate mechanisms of negative feedback as a representative of the widespread phenomenon of muti-level regulation of induced responses. We show that, under stochastic fly-bacteria encounters, an induced defense is favored when bacterial encounters are rare or uncertain, but in ways that depend on the bacterial proliferation rate. Our model also predicts that the specific negative regulators that optimize the induced response depend on the bacterial proliferation rate, linking negative feedback mechanisms to the factors that favor induction.
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  • 文章类型: Case Reports
    尽管在过去十年中,癌症治疗策略的疗效一直在稳步提高,此类治疗后的不良事件概况也变得越来越复杂.本报告描述了一名67岁的男性残胃癌伴肝浸润的病例。患者接受奥沙利铂和卡培他滨(CAPEOX方案)化疗,联合程序性细胞死亡蛋白-1(PD-1)抑制剂tislelizumab。治疗后,病人发冷,高烧面部潮红,接着是震惊。相关检查结果显示严重的多器官损伤,以及IL-6和降钙素原(PCT)水平显着升高。最初,患者被诊断为与tislelizumab引起的细胞因子释放综合征相关的免疫相关不良事件(irAEs)或严重的细菌感染.然而,当停止tislelizumab治疗并重新应用CAPEOX化疗方案时,类似症状复发。筛选后,最终确定奥沙利铂引起的严重超敏反应(HSR)是这些症状的根本原因.然后进行了文献综述,发现严重的奥沙利铂相关的HSR很少见,使目前的情况变得非典型。本案没有常见的HSR症状,如皮肤和呼吸道症状。然而,病人患有严重的多器官损伤,奥沙利铂化疗联合PD-1抑制剂时误诊为irAE。此外,这种明显严重的奥沙利铂相关HSR导致PCT水平显着增加,被误诊为严重的细菌感染,并阻止了糖皮质激素的使用。这个,反过来,加重了这个病人的伤害.
    Although the efficacy of treatment strategies for cancer have been improving steadily over the past decade, the adverse event profile following such treatments has also become increasingly complex. The present report described the case of a 67-year-old male patient with gastric stump carcinoma with liver invasion. The patient was treated with oxaliplatin and capecitabine (CAPEOX regimen) chemotherapy, combined with the programmed cell death protein-1 (PD-1) inhibitor tislelizumab. Following treatment, the patient suffered from chills, high fever and facial flushing, followed by shock. Relevant examination results revealed severe multiple organ damage, as well as a significant elevation in IL-6 and procalcitonin (PCT) levels. Initially, the patient was diagnosed with either immune-related adverse events (irAEs) associated with cytokine release syndrome caused by tislelizumab or severe bacterial infection. However, when tislelizumab treatment was stopped and the CAPEOX chemotherapy regimen was reapplied, similar symptoms recurred. Following screening, it was finally determined that severe hypersensitivity reaction (HSR) caused by oxaliplatin was the cause underlying these symptoms. A literature review was then performed, which found that severe oxaliplatin-related HSR is rare, rendering the present case atypical. The present case exhibited no common HSR symptoms, such as cutaneous and respiratory symptoms. However, the patient suffered from serious multiple organ damage, which was misdiagnosed as irAE when oxaliplatin chemotherapy combined with the PD-1 inhibitor was administered. In addition, this apparent severe oxaliplatin-related HSR caused a significant increase in PCT levels, which was misdiagnosed as severe bacterial infection and prevented the use of glucocorticoids. This, in turn, aggravated the damage in this patient.
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