Initial host-pathogen interactions explained by the Organism Prearranged Recognition Theory: fundamental role of saccharides

Herein based on literature available a hypothesis is provided about molecular basis for initial events in establishment interactions.This hypothesis asserts that:"recognition and interaction that occur between organisms is prearranged.There are membrane receptors with or without soluble components derived from the respective organisms that bridge specific interactions".Organisms'prearranged recognition theory(OPRT)can be specifically applied to host-microbe interactions where most microbes are coated(opsonised)by soluble components(opsonins)from the host,but there are also some microbes that can bypass host opsonization expressing receptors for the host cells or secreting host’s opsonin-like molecules.The receptors involved in organism's interactions,their specificity and repertoire depend on saccharides from glycoproteins,glycolipids,and polysaccharides(glycans)which are abundant extracellular components.Based in OPRT is possible to explain species-specific interactions and several other phenomena,such as hyper-infectivity,tissue tropism,differential sensitivity to disease depending on type O-blood,and tumoral cell promiscuity.The lipid raft domain in cellular membrane is proposed as the main location where interactions will trigger cellular responses.Possible scientific and biotechnology applications and alternative routes to modify organism's interactions and consequences are discussed.It is a novel hypothesis regarding the degree to which an organism's interactions are prearranged and the role of saccharides epitopes.

Novel insights into host-pathogen interactions of large yellow croakers(Larimichthys crocea)and pathogenic bacterium Pseudomonas plecoglossicida using time-resolved dual RNA-seq of infected spleens

Host-pathogen interactions are highly complex,involving large dynamic changes in gene expression during infection. These interactions are fundamental to understanding anti-infection immunity of hosts, as well as the pathogenesis of pathogens. For bacterial pathogens interacting with animal hosts, timeresolved dual RNA-seq of infected tissue is difficult to perform due to low pathogen load in infected tissue. In this study, an acute infection model of Larimichthys crocea infected by Pseudomonas plecoglossicida was established. The spleens of infected fish exhibited typical symptoms, with a maximum bacterial load at two days post-injection(dpi). Time-resolved dual RNA-seq of infected spleens was successfully applied to study hostpathogen interactions between L. crocea and P.plecoglossicida. The spleens of infected L. crocea were subjected to dual RNA-seq, and transcriptome data were compared with those of noninfected spleens or in vitro cultured bacteria. Results showed that pathogen-host interactions were highly dynamically regulated, with corresponding fluctuations in host and pathogen transcriptomes during infection. The expression levels of many immunogenes involved in cytokine-cytokine receptor,Toll-like receptor signaling, and other immunerelated pathways were significantly up-regulated during the infection period. Furthermore, metabolic processes and the use of oxygen in L. crocea were strongly affected by P. plecoglossicida infection. The WGCNA results showed that the metabolic process was strongly related to the entire immune process.For P. plecoglossicida, the expression levels of motility-related genes and flagellum assemblyrelated genes were significantly up-regulated. The results of this study may help to elucidate the interactions between L. crocea and P.plecoglossicida.

Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions

Active host-pathogen interactions take place during infection of human immunodeficiency virus type 1 (HIV-1). Outcomes of these interactions determine the efficiency of viral infection and subsequent disease progression. HIV- infected cells respond to viral invasion with various defensive strategies such as innate, cellular and humoral immune antiviral mechanisms. On the other hand, the virus has also developed various offensive tactics to suppress these host cellular responses. Among many of the viral offensive strategies, HIV-1 viral auxiliary proteins (Tat, Rev, Nef, Vif, Vpr and Vpu) play important roles in the host-pathogen interaction and thus have significant impacts on the outcome of HIV infection. One of the best examples is the interaction of Vif with a host cytidine deaminase APOBEC3G. Although specific roles of other auxiliary proteins are not as well described as Vif-APOBEC3G interaction, it is the goal of this brief review to summarize some of the preliminary findings with the hope to stimulate further discussion and investiga- tion in this exhilarating area of research.

New insights of Helicobacter pylori host-pathogen interactions: The triangle of virulence factors, epigenetic modifications and non-coding RNAs

Helicobacter pylori(H. pylori) is a model organism for understanding host-pathogen interactions and infection-mediated carcinogenesis. Gastric cancer and H. pylori colonization indicates the strong correlation. The progression and exacerbation of H. pylori infection are influenced by some factors of pathogen and host. Several virulence factors involved in the proper adherence and attenuation of immune defense to contribute the risk of emerging gastric cancer, therefore analysis of them is very important. H. pylori also modulates inflammatory and autophagy process to intensify its pathogenicity. From the host regard, different genetic factors particularly affect the development of gastric cancer. Indeed, epigenetic modifications, Micro RNA and long non-coding RNA received more attention. Generally, various factors related to pathogen and host that modulate gastric cancer development in response to H. pylori need more attention due to develop an efficacious therapeutic intervention. Therefore, this paper will present a brief overview of host-pathogen interaction especially emphases on bacterial virulence factors, interruption of host cellular signaling, the role of epigenetic modifications and non-coding RNAs.

A mathematic equation derived from host-pathogen interactions elucidates the significance of integrating modern medicine with traditional Chinese medicine to treat infectious diseases

The prognosis of infectious diseases is determined by host-pathogen interactions.Control of pathogens has been the central dogma of treating infectious diseases in modern medicine,but the pathogen-directed medicine is facing significant challenges,including a lack of effective antimicrobials for newly emerging pathogens,pathogen drug resistance,and drug side effects.Here,a mathematic equation(ter-med equation of host-pathogen interactions,HPI-Equation)is developed to dissect the key variables of hostpathogen interactions.It shows that control of pathogens does not necessarily lead to host recov-ery.Instead,a combination of promoting a host’s power of self-healing and balancing immune responses provides the best benefit for host.Moreover,the HPI-Equation elucidates the scientific basis of traditional Chinese medicine(TCM),a host-based medicine that treats infectious diseases by promot-ing self-healing power and balancing immune responses.The importance of self-healing power eluci-dated in the HPIEquation is confirmed by recent studies that the tolerance mechanism,which is discovered in plants and animals and conceptually similar to self-healing power,improves host survival without directly attacking pathogens.In summary,the HPI-Equation describes host-pathogen interac-tions with mathematical logic and precision;it translates the ancient wisdoms of TCM into apprehen-sible modern sciences and opens a new venue for integrating TCM and modern medicine for a future medicine.

酪氨酸激酶抑制剂调控宿主抗结核作用的研究进展

尽管现有的抗结核治疗方案在药物敏感结核病患者的治疗中取得了显著成效,但是药物毒性及耐药菌株的问题日益突出。因此,研究者们开始寻找新的药物和治疗策略,以期更好地治疗结核病。宿主导向治疗(host-directed therapy,HDT)可利用小分子化合物调节宿主的免疫反应,进而保护组织并清除病原体。HDT的主要目的是增强宿主的抗结核免疫功能,同时缩短传统抗生素治疗的时间,提高治疗效果,被视为治疗结核病的一种有前景的方法。酪氨酸激酶(protein tyrosine kinase,PTK)主要参与激活细胞信号转导,从而调节细胞生长、增殖、死亡等一系列生理生化过程。酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)是一种新型抗癌药物,在多种恶性肿瘤中可靶向过表达细胞通路,也可通过诱导自噬并激活其他信号通路发挥抗肿瘤活性。研究发现,TKI也可以在巨噬细胞中调节信号转导过程,降低胞内结核分枝杆菌的载量,具有巨大的治疗潜力。因此,TKI可作为HDT的潜在候选药物,应用于临床辅助治疗结核病。笔者将从PTK及信号转导入手,针对潜在的HDT治疗结核病的靶向药物研究进行综述,旨在为HDT疗法更好地应用于现有药物及研发新药,从而辅助治疗结核病提供参考。

Host-pathogen interaction after infection of Galleria mellonella with the filamentous fungus Beauveria bassiana

The filamentous fungus Beauveria bassiana is a natural pathogen of the greater wax moth Galleria mellonella.Infection with this fungus triggered systemic immune response in G.mellonella;nevertheless,the infection was lethal if spores entered the insect hemocel.We observed melanin deposition in the insect cuticle and walls of air bags,while the invading fungus interrupted tssue continuity.We have shown colonization of muscles,air bags,and finally colonization and complete destruction of the fat body-the main organ responsible for the synthesis of defense molecules in response to infection.This destruction was probably not caused by simple fungal growth,because the fat body was not destroyed during colonization with a human opportunistic pathogen Candida albicans.This may mean that the infecting fungus is able to destroy actively the insect's fat body as part of its virulence mechanism.Finally,we were unable to reduce the extremely high virulence of B.bassiana against G.mellonella by priming of larvae with thermally inactivated fungal spores.

互作转录组测序技术在感染性疾病研究中的应用现状

伴随着第二代、第三代测序技术的发展,转录组测序技术的测序深度不断增加,并且在现今的临床医学诊断和治疗中的应用越来越广。互作转录组测序技术(dual host-pathogen ribonucleic acid sequencing,Dual RNA-seq),可以同时提取2个(或多个)物种的RNA进行基因表达的互作分析,得到它们相互作用的机制。在医学上可用于分析感染患者或实验样本与病原体之间转录组水平的互作情况,从而评估患者或实验样本基因表达状态并可用于药物预测。本文主要综述了Dual RNA-seq的工作原理及其在传染病领域的应用,并介绍了其与单细胞测序和非编码RNA分析结合的进展,以期对感染相关的临床和研究工作提供参考。

肺炎克雷伯菌外膜囊泡的研究进展

肺炎克雷伯菌是一种典型的肠杆菌科条件致病菌,也是六大超级细菌“ESKAPE”中的一员,通常定植在人类呼吸道和肠道,可引起肺炎、脑膜炎和血流感染等多种感染。外膜囊泡(OMV)是由革兰阴性菌自发分泌的具有生物学活性的囊泡状结构,含有多糖、外膜蛋白和核酸等成分。现有研究证实肺炎克雷伯菌OMV在病原菌致病机制、传递效应因子以及与宿主相互作用等方面发挥重要作用。文章主要围绕肺炎克雷伯菌OMV的基本信息、生物学功能以及生物医学应用等方面进行讨论,对肺炎克雷伯菌OMV的最新研究进展进行综述。

不同症状类型苜蓿病毒病AMV病原检测及其寄主范围测定

为明确采自田间不同症状类型苜蓿病毒病病样中苜蓿花叶病毒(alfalfa mosaic virus,AMV)的带毒情况、症状表现与叶绿素含量的相关性及AMV的寄主范围,本试验通过田间调查采样、症状归类、丙酮乙醇混合液法和双抗体夹心酶联免疫吸附测定(DAS-ELISA)法对不同病样的叶绿素和AMV含量进行测定和检测,并对提纯至不同症状类型病样中AMV对9科32种植物的致病性进行测定。结果表明田间苜蓿病毒病病样有轻花叶、重花叶、叶片边缘褪绿黄化型和叶片畸形皱缩花叶矮化型4种症状类型,均带有AMV,且叶绿素含量、AMV含量与症状表现之间具有正相关性,症状表现最严重的叶片畸形皱缩花叶矮化型病样的叶绿素a、b、总叶绿素含量均比对照低58.00%以上,类胡萝卜素含量比对照高134.06%,AMV含量最高,为252.96 pg·mL^(-1);寄主范围测定表明AMV可侵染7科27种植物,对西葫芦致病性最强,症状表现为局部枯斑,30 d时AMV浓度为316.19 pg·mL^(-1)。

冯晓纯教授用主客交病理论治疗小儿腺样体肥大经验

儿童腺样体肥大是儿科常见病、多发病,目前西医多采取有创治疗,但术后易复发、感染,不易被接受。中医药保守治疗可缩小腺样体体积,减轻鼻塞、打鼾、开口呼吸等临证症状,可使部分患儿避免手术、复发患儿避免二次手术,因此被广大患儿及家长接受。冯晓纯教授根据中医经典“主客交病”理论,采用“疏瘀和营,入阴搜邪”法,应用加减三甲散治疗本病,临床取得了显著效果。

肿瘤内细菌调控肿瘤细胞可塑性研究进展与展望

病原微生物与宿主细胞的交流与互作机制是生物医学领域的重要科学问题。随着单细胞分析和多组学研究模式的拓展,该领域迎来了新的科研突破。最新研究表明,肿瘤内细菌通过与肿瘤细胞及肿瘤免疫细胞互作改变肿瘤的演进和可塑性。为此,进一步解析肿瘤内细菌与宿主细胞之间的相互作用机制有望为靶向干预肿瘤发展与演进提供新的思路。本文综述了肿瘤内细菌与肿瘤细胞可塑性的研究进展,并展望了未来在制定肿瘤的精准治疗和新的靶向策略方面的潜在启示。

病原体感染对物种间资源竞争的影响——基于资源竞争理论

病原体感染对种间竞争的影响可能是因为改变了宿主的资源利用过程,然而竞争模型(Lotka-Volterra)由于参数化竞争系数而忽略了资源的动态变化过程,因此基于此类模型的研究无法揭示病原体对宿主资源利用的影响。基于Tilman的资源竞争理论构建了病原体感染一个物种的资源竞争模型,通过分析宿主物种资源利用效率的变化探讨了病原体对种间竞争的影响。结果表明:(1)病原体降低了宿主对资源的消耗率(消费矢量变短),抬高了对资源的最低需求(零等倾线上移),这意味着宿主的竞争力减弱;(2)虽然感染影响了竞争物种的密度,但不会改变共存物种的共存状态;(3)病原体可以使宿主物种的竞争对手更容易入侵,形成共存局面,极大地扩大了竞争物种共存的参数范围,本质上促进了物种多样性维持;(4)病原体的传播率和毒性也复杂地影响了竞争物种共存,传播率越大越能促进物种共存,而中等强度毒性最能促进物种共存。研究结果明确了病原体对物种资源利用模式的潜在改变,强调了病原体在物种共存和生物多样性维持中的重要性。

链格孢毒素化学结构、毒性效应和检测方法研究进展

链格孢(Alternaria sp.)是自然界常见的真菌微生物,也是造成许多农作物、蔬菜和水果病害的病原微生物。链格孢毒素是链格孢产生的多种次级代谢物的总称,其作用机制是当前研究中的热点问题。链格孢毒素影响植物宿主亚细胞结构,包括叶绿体、线粒体、质膜、细胞核等。根据链格孢与宿主的作用特性,可将链格孢毒素分为宿主特异性毒素(Host⁃specific toxin,HST)和宿主非特异性毒素(Non⁃host⁃specific toxin,nHST)两类。综述了多种重要的HST和nHST的化学结构、毒性效应和检测技术,比较了不同种类链格孢毒素化学结构特征异同、毒性效应靶向位点差异、不同检测方法的优劣,为控制链格孢病害和开发毒素检测方法提供参考。

细菌及病毒感染的宿主导向治疗

病原菌对抗菌药物耐药性的逐年增加及新型未知致病微生物的频繁出现与流行严重威胁着人类健康,因此迫切需要开发各种新型抗感染药物。宿主导向的抗细菌和病毒感染治疗(HDT)可作用于宿主-病原体相互作用中各个阶段的宿主组分或因素,相比于直接靶向病原微生物本身的药物,HDT具有研发周期较短、研发成本较低、治疗范围广以及能有效防止或减缓抗菌药物耐药性发展的优势。鉴于大部分HDT方法基于宿主-病原体相互作用和失衡理论,该文从阻止病原微生物对细胞的入侵、干扰病原微生物在宿主细胞内的持续存在、提升宿主的抗感染反应及调节过度炎症反应等几个方面对HDT药物进行介绍。

后疫情时代病原学与宿主防御学“双线混融模式”实验教学探索

后疫情时代,线上线下深度融合的混合式教学模式将成为信息化发展的必然趋势。本文以病原学与宿主防御学实验教学为例,提出以“双线混融模式”为基础,探索利用虚拟仿真和互联网平台,结合临床案例与综合性实验,合理融入课程思政元素的新途径,有效发挥整合医学实验课程的作用,加强学生对医学专业知识的掌握,提升整合医学实验教学在数字化进程中的步伐,为整合医学教育同行开辟新思路,对推动高素质的应用型医学人才培养具有积极作用。

宏基因组测序技术检测血流感染样本去宿主干扰效应四种预处理方法的比较

目的探讨不同去宿主方法对血流感染样本中病原微生物检测的影响。方法以浓度分别为10^(5),10^(3),10^(2)和10CFU/ml的模拟金黄色葡萄球菌血流感染样本为研究对象,将检测分为全血组和血浆组,使用宏基因组测序(metagenomic next generation sequencing,mNGS)比较Saponin法、Wash法、CD45法和MolYsis法四种预处理方法的病原微生物reads检出数和占比,以评估不同方法的去宿主效率。结果血流感染病原微生物初始浓度在10^(3)CFU/ml以下的微生物检出占比小于0.15%。四种去宿主方法中,Saponin法reads检出数最多,病原微生物检出占比最高,血浆组检测结果占比可提升至18%以上;Wash法及CD45法相比直接提取法病原微生物reads检出数均未显著增加,MolYsis法的reads检出数水平有明显增高。血浆组病原微生物reads检出数多于全血组,去宿主方法可明显提高病原微生物的丰度。结论对比四种去宿主方法的mNGS检测结果,Saponin法可明显去除宿主核酸,提高病原微生物的reads检出数,尤其血浆组去宿主效果最好。

大脑的多任务:对病毒感染的神经胶质反应和相应的感染后神经后遗症

许多病毒感染会导致急性和慢性神经系统疾病,从而导致大脑皮质功能退化。虽然进入中枢神经系统(CNS)的嗜神经病毒可能通过感染神经元或其支持细胞直接诱导脑损伤,但它们也会通过间接神经免疫机制改变大脑功能,这种机制可能会破坏血脑屏障(BBB)、损伤突触,并产生神经毒性星形胶质细胞和小胶质细胞,阻止神经环路的恢复。非神经侵袭性、神经毒性病毒也可能在神经胶质细胞中引发异常反应,包括那些干扰运动和感觉行为、记忆编码、执行功能的反应。来自人类和动物研究的越来越多的证据表明,即使在没有神经侵袭的情况下,提高先天免疫分子水平的神经保护性抗病毒反应也会导致正常的神经免疫过程失调,这种情况可能在病毒清除后持续存在。在本综述中,我们讨论了选择性新出现和再次出现的RNA病毒如何诱导神经免疫反应,从而导致包括视觉空间识别、学习和记忆以及运动控制在内的高级过程功能障碍。识别使神经免疫系统恢复稳态的治疗靶点对于预防病毒诱导的神经退行性疾病至关重要。

猴痘病毒的分类、演化和宿主范围:痘病毒的系统综述和分析

近20年来,偶发的感染人类的猴痘疾病严重影响了公共卫生和经济。啮齿类动物是猴痘病毒(MPXV)在自然界的主要宿主。MPXV可以通过直接接触传播至人并引起自限性感染,出现皮疹和淋巴结症状。本世纪初,美国报道了第一例在非洲以外地区人感染MPXV的病例,此后,猴痘逐步在全世界流行,并成为严重的公共威胁。随着病毒检测和测序技术的发展,许多新的痘病毒被发现,从而丰富了痘病毒科的多样性。本综述对MPXV以及痘病毒科中的其他病毒的最新分类、宿主范围、基因组结构特点、致病性以及遗传进化关系进行了全面概述。这些信息将促进我们对痘病毒的遗传进化关系和传播的了解,并且对未来病毒的研究和疾病的控制提供帮助。

解脲支原体的致病性研究进展

解脲支原体(Ureaplasma urealyticum,UU)是一类与非淋球菌性尿道炎、不孕不育和胎膜早破及新生儿支气管肺泡发育不良等多种疾病相关的病原体。UU的致病性成为近年来的研究热点,主要包括两个方面:其一可能存在的多种潜在的致病因子或致病岛,其二与致病性强弱密切相关的UU的生物群、血清型和浓度及宿主自身的免疫力。文中就UU的致病性进行了详细综述。