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Multidrug-Resistant Tuberculosis in Côte d'Ivoire from 1995 to 2016: Results of National Surveys. 1995年至2016年Côte科特迪瓦耐多药结核病:国家调查结果
Pub Date : 2018-08-16 eCollection Date: 2018-09-28 DOI: 10.1556/1886.2018.00001
Kouassi N'Guessan, Timothée Ouassa, Anna S Dean, Riccardo Alagna, Guy Damien Adagra, Valeri Ibode, Daniela M Cirillo, Jacquemin Kouakou

Setting: Tuberculosis (TB) drug resistance survey was conducted in 2016-2017 to estimate the burden of drug-resistant TB in Côte d'Ivoire.

Design: A cross-sectional cluster-based survey was conducted. All eligible smear positive patients were interviewed using a structured questionnaire to collect clinical and sociodemographic information and tested by the Xpert Mycobacterium tuberculosis/rifampicin (MTB/RIF) assay. If resistant to rifampicin, solid and liquid cultures were performed. Phenotypic drug susceptibility testing (DST) was conducted in liquid medium for rifampicin, isoniazid, ethambutol, streptomycin, ofloxacin, and amikacin.

Results: Of the 1105 sputum smear positive patients enrolled, 995 new and 100 previously treated patients were positive for Mycobacterium tuberculosis complex by Xpert. Proportion of patients with rifampicin resistance was 4.6% (95% CI: 2.4-6.7) and 22% (95% CI: 13.7-30.3), respectively, for new and previously treated patients. Second-line DST results were available for most rifampicin-resistant patients. None were resistant to amikacin, only two were ofloxacin-resistant. Apart from the antecedent of previously treatment for TB, no other risk factors for rifampicin resistance were detected.

Conclusion: Prevalence of rifampicin resistance among TB patients in Côte d'Ivoire is higher than that in other countries in the region. Surveillance of drug resistance, through an expanded GeneXpert network, and programmatic management of drug-resistant TB (PMDT) must be strengthened in Côte d'Ivoire.

背景:2016-2017年开展了结核病耐药性调查,以估计Côte科特迪瓦耐药结核病的负担。设计:采用横断面聚类调查。采用结构化问卷对所有符合条件的涂片阳性患者进行访谈,以收集临床和社会人口学信息,并通过Xpert结核分枝杆菌/利福平(MTB/RIF)试验进行检测。如果对利福平耐药,进行固体和液体培养。在液体培养基中对利福平、异烟肼、乙胺丁醇、链霉素、氧氟沙星、阿米卡星进行表型药敏试验(DST)。结果:纳入的1105例痰涂片阳性患者中,新患者995例,既往患者100例,Xpert检测结核分枝杆菌复体阳性。新治疗和既往治疗的患者中,利福平耐药患者比例分别为4.6% (95% CI: 2.4-6.7)和22% (95% CI: 13.7-30.3)。二线DST结果可用于大多数利福平耐药患者。没有人对阿米卡星耐药,只有两人对氧氟沙星耐药。除了以前接受过结核病治疗外,未发现利福平耐药的其他危险因素。结论:Côte科特迪瓦结核病患者对利福平的耐药性高于该地区其他国家。必须在Côte科特迪瓦加强通过扩大的GeneXpert网络监测耐药性以及对耐药结核病的规划管理。
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引用次数: 7
Determination of Antimicrobial Activity of Some Commercial Fruit (Apple, Papaya, Lemon and Strawberry) Against Bacteria Causing Urinary Tract Infection. 测定一些商业水果(苹果、木瓜、柠檬和草莓)对引起尿路感染的细菌的抗菌活性
Pub Date : 2018-08-16 eCollection Date: 2018-09-28 DOI: 10.1556/1886.2018.00014
Sabiha Jahan Liya, Romana Siddique

Urinary Tract Infection (UTI) is a worldwide phenomenon in modern times, in which the dependency on antibiotics for its treatment is increasing. The current study was conducted in order to find alternatives to antibiotics by investigating some commercial fruits for their antimicrobial activity. The fruits in this study included green apple (Malus domestica), papaya (Carica papaya), lemon (Citrus limon), and strawberry (Fragaria ananassa), which were used to prepare methanolic and ethanolic extracts through Soxhlet extraction technique. The extracts were used against bacteria that cause UTI, and five different strains were selected: E. coli (ATCC: 15922), E. coli (ATCC: 25922), Pseudomonas aeruginosa (ATCC: 27853), Enterococcus faecalis (ATCC: 29212), and Klebsiella pneumoniae. Antimicrobial tests of the extracts were conducted by following the agar well diffusion method, where ciprofloxacin was used as a positive control, and autoclaved distilled water was used as a negative control. Among the fruits, apple and papaya extracts did not show any zone of inhibition against any of the tested bacteria. However, both lemon and strawberry extracts showed inhibition zone against all of the mentioned bacteria. The ethanolic extracts of lemon and strawberry were more potent than their methanolic extracts. Lemon ethanolic extract showed the highest zone of inhibition against Pseudomonas aeruginosa (ATCC: 27853) (18.34 ± 0.58) and lowest one against Klebsiella pneumoniae (16.00 ± 1.00). Strawberry ethanolic extracts showed the highest zone of inhibition against Pseudomonas aeruginosa (ATCC: 27853) (16.33 ± 0.58) and the lowest one against Klebsiella pneumoniae (13.33 ± 0.58). As antibiotic resistance is paving the way for multi-drug resistant bacteria, the results of lemon and strawberry can be considered to be used as an antimicrobial agent in treating urinary tract infections.

尿路感染(UTI)是当今世界的一个普遍现象,其治疗对抗生素的依赖性与日俱增。本研究通过调查一些商业水果的抗菌活性,寻找抗生素的替代品。本研究中的水果包括青苹果(Malus domestica)、木瓜(Carica papaya)、柠檬(Citrus limon)和草莓(Fragaria ananassa),通过索氏提取技术制备甲醇和乙醇提取物。萃取物用于对抗导致UTI的细菌,并选择了五种不同的菌株:大肠杆菌(ATCC:15922)、大肠杆菌(ATCC:25922)、铜绿假单胞菌(ATCC:27853)、粪肠球菌(ATCC:29212)和肺炎克雷伯菌。提取物的抗菌试验采用琼脂井扩散法,以环丙沙星为阳性对照,高压蒸馏水为阴性对照。在水果中,苹果和木瓜提取物对任何一种受测细菌都没有抑制作用。然而,柠檬和草莓萃取物对上述所有细菌都有抑制作用。柠檬和草莓的乙醇提取物比它们的甲醇提取物更有效。柠檬乙醇提取物对铜绿假单胞菌(ATCC:27853)的抑制面积最大(18.34 ± 0.58),对肺炎克雷伯菌的抑制面积最小(16.00 ± 1.00)。草莓乙醇提取物对铜绿假单胞菌(ATCC: 27853)的抑制面积最大(16.33 ± 0.58),对肺炎克雷伯菌的抑制面积最小(13.33 ± 0.58)。由于抗生素耐药性正在为多重耐药菌铺平道路,柠檬和草莓的结果可被视为治疗尿路感染的抗菌剂。
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引用次数: 0
Function of Serine Protease HtrA in the Lifecycle of the Foodborne Pathogen Campylobacter jejuni. 丝氨酸蛋白酶HtrA在食源性致病菌空肠弯曲杆菌生命周期中的作用。
Pub Date : 2018-07-17 eCollection Date: 2018-09-28 DOI: 10.1556/1886.2018.00011
Manja Boehm, Daniel Simson, Ulrike Escher, Anna-Maria Schmidt, Stefan Bereswill, Nicole Tegtmeyer, Steffen Backert, Markus M Heimesaat

Campylobacter jejuni is a major food-borne zoonotic pathogen, responsible for a large proportion of bacterial gastroenteritis cases, as well as Guillian-Barré and Miller-Fisher syndromes. During infection, tissue damage is mainly caused by bacteria invading epithelial cells and traversing the intestinal barrier. C. jejuni is able to enter the lamina propria and the bloodstream and may move into other organs, such as spleen, liver, or mesenteric lymph nodes. However, the involved molecular mechanisms are not fully understood. C. jejuni can transmigrate effectively across polarized intestinal epithelial cells mainly by the paracellular route using the serine protease high-temperature requirement A (HtrA). However, it appears that HtrA has a dual function, as it also acts as a chaperone, interacting with denatured or misfolded periplasmic proteins under stress conditions. Here, we review recent progress on the role of HtrA in C. jejuni pathogenesis. HtrA can be transported into the extracellular space and cleaves cell-to-cell junction factors, such as E-cadherin and probably others, disrupting the epithelial barrier and enabling paracellular transmigration of the bacteria. The secretion of HtrA is a newly discovered strategy also utilized by other pathogens. Thus, secreted HtrA proteases represent highly attractive targets for anti-bacterial treatment and may provide a suitable candidate for vaccine development.

空肠弯曲杆菌是一种主要的食源性人畜共患病原体,造成很大比例的细菌性肠胃炎病例,以及吉利安-巴罗尔斯综合征和米勒-费舍尔综合征。在感染过程中,组织损伤主要是由细菌侵入上皮细胞并穿过肠道屏障引起的。空肠梭菌能够进入固有层和血液,并可能进入其他器官,如脾脏、肝脏或肠系膜淋巴结。然而,所涉及的分子机制尚不完全清楚。空肠梭菌主要通过丝氨酸蛋白酶高温需要A (HtrA)的胞旁途径在极化肠上皮细胞间进行有效的迁移。然而,HtrA似乎具有双重功能,因为它也作为伴侣,在应激条件下与变性或错误折叠的质周蛋白相互作用。本文就HtrA在空肠梭菌发病机制中的作用作一综述。HtrA可以被运输到细胞外空间,分裂细胞间连接因子,如E-cadherin等,破坏上皮屏障,使细菌能够胞外转运。HtrA的分泌是一种新发现的策略,也被其他病原体利用。因此,分泌的HtrA蛋白酶代表了抗菌治疗的高度有吸引力的靶点,并可能为疫苗开发提供合适的候选物。
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引用次数: 29
Humanization of the Blood-Brain Barrier Transporter ABCB1 in Mice Disrupts Genomic Locus - Lessons from Three Unsuccessful Approaches. 血脑屏障转运体 ABCB1 在小鼠中的人源化破坏了基因组位点--从三种不成功的方法中汲取的教训。
Pub Date : 2018-07-06 eCollection Date: 2018-09-28 DOI: 10.1556/1886.2018.00008
Markus Krohn, Thomas Wanek, Marie-Claude Menet, Andreas Noack, Xavier Declèves, Oliver Langer, Wolfgang Löscher, Jens Pahnke

ATP-binding cassette (ABC) transporters are of major importance for the restricted access of toxins and drugs to the human body. At the body's barrier tissues like the blood-brain barrier, these transporters are highly represented. Especially, ABCB1 (P-glycoprotein) has been a priority target of pharmaceutical research, for instance, to aid chemotherapy of cancers, therapy resistant epilepsy, and lately even neurodegenerative diseases. To improve translational research, the humanization of mouse genes has become a popular tool although, like recently seen for Abcb1, not all approaches were successful. Here, we report the characterization of another unsuccessful commercially available ABCB1 humanized mouse strain. In vivo assessment of transporter activity using positron emission tomography imaging revealed a severe reduction of ABCB1 function in the brain of these mice. Analyses of brain mRNA and protein expression showed that the murine Abcb1a gene is still expressed in homozygous humanized animals while expression of the human gene is minimal. Promoter region analyses underpinned that the introduced human gene might dysregulate normal expression and provided insights into the regulation of both transcription and translation of Abcb1a. We conclude that insertion of the human coding DNA sequence (CDS) into exon 3 instead of exon 2 most probably represents a more promising strategy for Abcb1a humanization.

ATP 结合盒(ABC)转运体对于限制毒素和药物进入人体至关重要。在血脑屏障等人体屏障组织中,这些转运体具有很高的代表性。特别是 ABCB1(P-糖蛋白),它一直是药物研究的优先目标,例如,用于辅助癌症化疗、抗药性癫痫以及最近的神经退行性疾病。为了改进转化研究,小鼠基因的人源化已成为一种流行的工具,不过,就像最近在 Abcb1 上看到的那样,并非所有的方法都是成功的。在此,我们报告了另一个不成功的商业化 ABCB1 人源化小鼠品系的特征。利用正电子发射断层扫描成像对转运体活性进行的体内评估显示,这些小鼠大脑中的 ABCB1 功能严重减弱。对大脑 mRNA 和蛋白质表达的分析表明,在同卵人源化动物中,小鼠的 Abcb1a 基因仍在表达,而人类基因的表达则微乎其微。启动子区域分析证实了引入的人类基因可能会导致正常表达失调,并为了解 Abcb1a 的转录和翻译调控提供了线索。我们的结论是,将人类编码 DNA 序列(CDS)插入第 3 号外显子而不是第 2 号外显子很可能是一种更有前途的 Abcb1a 人源化策略。
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引用次数: 0
Seroepidemiology of Leptospira Infection in Backyard Pigs in Durango State, Mexico. 墨西哥杜兰戈州家养猪钩端螺旋体感染的血清流行病学研究。
Pub Date : 2018-07-06 eCollection Date: 2018-09-28 DOI: 10.1556/1886.2018.00009
Anabel Cruz-Romero, Cosme Alvarado-Esquivel, Dora Romero-Salas, Ángel Osvaldo Alvarado-Félix, Sokani Sánchez-Montes, Jesús Hernández-Tinoco, Luis Francisco Sánchez-Anguiano

Purpose: This study aimed to determine the seroprevalence and correlates of Leptospira IgG antibodies in backyard pigs in the northern Mexican state of Durango. We performed a cross-sectional study of 305 backyard pigs. Anti-Leptospira IgG antibodies were detected using microscopic agglutination assay (MAT) with a panel of 12 Leptospira antigens.

Results: Overall, antibodies against Leptospira (any of the 12 Leptospira serovars examined) were found in 186 (61.0%) of the 305 pigs studied. Seropositive pigs were found on 80 (70.2%) of the 114 properties surveyed. The predominant serovar was Leptospira interrogans Pomona (n = 55); followed by Leptospira noguchii Lousiana and Leptospira santarosai Tarassovi (n = 53 each); L. interrogans Bataviae (n = 47); Leptospira biflexa Semaranga and L. interrogans Hebdomadis (n = 36 each); L. interrogans Pyrogenes (n = 30); L. interrogans Djasiman (n = 20); Leptospira borgpetersenii Ballum (n = 11); L. noguchii Panama and L. interrogans Canicola (n = 5 each); and L. borgpetersenii Mini (n = 2). Logistic regression showed that seropositivity was associated with low (<1000 m above sea level) altitude (odds ratio [OR] = 3.24; 95% confidence interval [CI]: 2.01-5.20; P < 0.001).

Conclusions: This is the first report of Leptospira exposure in backyard pigs in Mexico and of an association between Leptospira exposure in pigs and altitude. Backyard pigs represent a high-risk group for Leptospira exposure.

目的:本研究旨在测定墨西哥北部杜兰戈州后院猪钩端螺旋体IgG抗体的血清阳性率及其相关因素。我们对305头后院猪进行了横断面研究。用显微镜凝集法(MAT)检测12种钩端螺旋体抗原的抗钩端螺旋体IgG抗体。结果:总体而言,305头猪中有186头(61.0%)检测到钩端螺旋体抗体(检测的12种血清型中的任何一种)。114种猪种中有80头(70.2%)呈血清阳性。主要血清型为可疑钩端螺旋体(55例);其次是路易斯安那野口钩端螺旋体和塔拉索维钩端螺旋体(各53例);Bataviae (n = 47);双歧钩端螺旋体和疑问钩端螺旋体(各36例);热生菌(n = 30);L.询问者Djasiman (n = 20);伯格彼得钩端螺旋体(n = 11);L. noguchi巴拿马和L.审讯犬(各n = 5);borgpetersenii Mini (n = 2)。Logistic回归分析显示血清阳性与低浓度相关(P < 0.001)。结论:这是墨西哥后院猪钩端螺旋体暴露的第一份报告,以及猪钩端螺旋体暴露与海拔之间的关系。后院猪是钩端螺旋体接触的高危群体。
{"title":"Seroepidemiology of <i>Leptospira</i> Infection in Backyard Pigs in Durango State, Mexico.","authors":"Anabel Cruz-Romero,&nbsp;Cosme Alvarado-Esquivel,&nbsp;Dora Romero-Salas,&nbsp;Ángel Osvaldo Alvarado-Félix,&nbsp;Sokani Sánchez-Montes,&nbsp;Jesús Hernández-Tinoco,&nbsp;Luis Francisco Sánchez-Anguiano","doi":"10.1556/1886.2018.00009","DOIUrl":"https://doi.org/10.1556/1886.2018.00009","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to determine the seroprevalence and correlates of <i>Leptospira</i> IgG antibodies in backyard pigs in the northern Mexican state of Durango. We performed a cross-sectional study of 305 backyard pigs. Anti-<i>Leptospira</i> IgG antibodies were detected using microscopic agglutination assay (MAT) with a panel of 12 <i>Leptospira</i> antigens.</p><p><strong>Results: </strong>Overall, antibodies against <i>Leptospira</i> (any of the 12 <i>Leptospira</i> serovars examined) were found in 186 (61.0%) of the 305 pigs studied. Seropositive pigs were found on 80 (70.2%) of the 114 properties surveyed. The predominant serovar was <i>Leptospira interrogans</i> Pomona (<i>n</i> = 55); followed by <i>Leptospira noguchii</i> Lousiana and <i>Leptospira santarosai</i> Tarassovi (<i>n</i> = 53 each); <i>L. interrogans</i> Bataviae (<i>n</i> = 47); Leptospira <i>biflexa</i> Semaranga and <i>L. interrogans</i> Hebdomadis (<i>n</i> = 36 each); <i>L. interrogans</i> Pyrogenes (<i>n</i> = 30); <i>L. interrogans</i> Djasiman (<i>n</i> = 20); <i>Leptospira borgpetersenii</i> Ballum (<i>n</i> = 11); <i>L. noguchii</i> Panama and <i>L. interrogans</i> Canicola (<i>n</i> = 5 each); and <i>L. borgpetersenii</i> Mini (<i>n</i> = 2). Logistic regression showed that seropositivity was associated with low (<1000 m above sea level) altitude (odds ratio [OR] = 3.24; 95% confidence interval [CI]: 2.01-5.20; <i>P</i> < 0.001).</p><p><strong>Conclusions: </strong>This is the first report of <i>Leptospira</i> exposure in backyard pigs in Mexico and of an association between <i>Leptospira</i> exposure in pigs and altitude. Backyard pigs represent a high-risk group for <i>Leptospira exposure</i>.</p>","PeriodicalId":11929,"journal":{"name":"European Journal of Microbiology & Immunology","volume":"8 3","pages":"87-90"},"PeriodicalIF":0.0,"publicationDate":"2018-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1556/1886.2018.00009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36649223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 5
Impact of MRSA on the Military Medical Service and Diagnostic Point-of-Care Options for the Field Setting. MRSA对军队医疗服务和战地诊断点选择的影响。
Pub Date : 2018-06-20 eCollection Date: 2018-06-25 DOI: 10.1556/1886.2018.00012
Hagen Frickmann

Methicillin-resistant Staphylococcus aureus (MRSA) poses an infection risk for international military deployments. In the presented mini-review, the history of MRSA in the medical service and modern warfare is highlighted. To allow rapid diagnosis, various molecular diagnostic point-of-care solutions are available. Most evaluation studies, however, are focused on screening swabs rather than clinical materials and evaluation data from harsh environments are widely lacking. Accordingly, studies with complex sample materials under difficult environmental conditions, e.g., in the desert or in the tropics, are desirable to close this gap of knowledge regarding the diagnostic reliability of such modern molecular point-of-care devices.

耐甲氧西林金黄色葡萄球菌(MRSA)对国际军事部署构成感染风险。在目前的小型回顾,MRSA在医疗服务和现代战争的历史是突出的。为了允许快速诊断,各种分子诊断护理点解决方案是可用的。然而,大多数评估研究都侧重于筛选拭子,而不是临床材料,并且普遍缺乏来自恶劣环境的评估数据。因此,需要在困难的环境条件下,例如在沙漠或热带地区,对复杂的样品材料进行研究,以缩小这种现代分子护理点设备的诊断可靠性方面的知识差距。
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引用次数: 5
Anti-inflammatory Effects of the Octapeptide NAP in Human Microbiota-Associated Mice Suffering from Subacute Ileitis. 八肽NAP对患有亚急性Ileitis的人类微生物群相关小鼠的抗炎作用。
Pub Date : 2018-05-23 DOI: 10.1556/1886.2018.00006
Ulrike Escher, Eliezer Giladi, Ildikò R Dunay, Stefan Bereswill, Illana Gozes, Markus M Heimesaat

The octapeptide NAP is well known for its neuroprotective properties. We here investigated whether NAP treatment could alleviate pro-inflammatory immune responses during experimental subacute ileitis. To address this, mice with a human gut microbiota were perorally infected with one cyst of Toxoplasma gondii (day 0) and subjected to intraperitoneal synthetic NAP treatment from day 1 until day 8 postinfection (p.i.). Whereas placebo (PLC) control animals displayed subacute ileitis at day 9 p.i., NAP-treated mice exhibited less pronounced pro-inflammatory immune responses as indicated by lower numbers of intestinal mucosal T and B lymphocytes and lower interferon (IFN)-γ concentrations in mesenteric lymph nodes. The NAP-induced anti-inflammatory effects were not restricted to the intestinal tract but could also be observed in extra-intestinal including systemic compartments, given that pro-inflammatory cytokines were lower in liver, kidney, and lung following NAP as compared to PLC application, whereas at day 9 p.i., colonic and serum interleukin (IL)-10 concentrations were higher in the former as compared to the latter. Remarkably, probiotic commensal bifidobacterial loads were higher in the ileal lumen of NAP as compared to PLC-treated mice with ileitis. Our findings thus further support that NAP might be regarded as future treatment option directed against intestinal inflammation.

八肽NAP以其神经保护特性而闻名。我们在这里研究了NAP治疗是否可以减轻实验性亚急性回肠炎期间的促炎免疫反应。为了解决这一问题,将具有人类肠道微生物群的小鼠全程感染一个弓形虫囊肿(第0天),并从感染后第1天到第8天(p.i.)接受腹膜内合成NAP治疗。而安慰剂(PLC)对照动物在p.i.第9天表现出亚急性回肠炎。,NAP处理的小鼠表现出不太明显的促炎免疫反应,表现为肠粘膜T和B淋巴细胞数量减少以及肠系膜淋巴结中干扰素(IFN)-γ浓度降低。NAP诱导的抗炎作用不仅限于肠道,还可以在肠外(包括全身)区室中观察到,因为与PLC应用相比,NAP后肝、肾和肺中的促炎细胞因子较低,而在第9天。,结肠和血清白细胞介素(IL)-10浓度前者高于后者。值得注意的是,与PLC治疗的患有回肠炎的小鼠相比,NAP回肠腔内的益生菌共生双歧杆菌负荷更高。因此,我们的研究结果进一步支持NAP可能被视为未来针对肠道炎症的治疗选择。
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引用次数: 16
Effects of Live and Heat-Inactivated E. coli Strains and Their Supernatants on Immune Regulation in HT-29 Cells. 活的和热灭活的大肠杆菌菌株及其上清液对HT-29细胞免疫调节的影响。
Pub Date : 2018-05-05 DOI: 10.1556/1886.2018.00004
Christian Zimmermann, Marius Schild, Clemens Kunz, Kurt Zimmermann, Sabine Kuntz

Probiotics are considered to have a beneficial impact on humans, but in some cases, administration of live microorganisms might be risky. In the present study, immunomodulatory effects of different Escherichia coli strains and their super-natants were examined under different inflammatory conditions with living and heat-inactivated strains. HT-29 cells were incubated with E. coli strains (S2-G1, S2-G3, S2-G4 and S2-G8) and their supernatants with or without stimulation with tumor necrosis factor alpha (TNF-α) or interleukin (IL)-1β. Quantification of IL-8 secretion and gene expression was performed by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR). IL-8 secretion by TNF-α- and IL-1β-stimulated cells was attenuated by all four live strains. In contrast, heat inactivation resulted in an elevated IL-8 expression and secretion in unstimulated cells and did not maintain the anti-inflammatory effect of live bacteria in cytokine-stimulated cells. The supernatant of the live S2-G3 led to an elevated IL-8 secretion in unstimulated and IL-1β-stimulated cells but not in TNF-α-stimulated cells. Live bacteria of all strains might induce an immunosuppressive effect after stimulation of HT-29 cells, whereas heat inactivation and the supernatant seem to induce an elevated immune response. These findings might have an impact depending on the indication and purpose of administration.

益生菌被认为对人类有有益的影响,但在某些情况下,使用活微生物可能有风险。在本研究中,用活菌株和热灭活菌株在不同炎症条件下检测了不同大肠杆菌菌株及其上清液的免疫调节作用。HT-29细胞与大肠杆菌菌株(S2-G1、S2-G3、S2-G4和S2-G8)及其上清液在肿瘤坏死因子-α(TNF-α)或白细胞介素-1β刺激或不刺激下孵育。通过酶联免疫吸附试验(ELISA)和实时聚合酶链式反应(PCR)对IL-8分泌和基因表达进行定量。TNF-α和IL-1β刺激的细胞分泌的IL-8被所有四种活菌株减弱。相反,热失活导致未刺激细胞中IL-8的表达和分泌升高,并且在细胞因子刺激的细胞中没有维持活细菌的抗炎作用。活S2-G3的上清液导致未刺激和IL-1β刺激的细胞中IL-8分泌增加,但TNF-α刺激的细胞不分泌。所有菌株的活细菌在刺激HT-29细胞后可能诱导免疫抑制作用,而热灭活和上清液似乎诱导免疫反应升高。这些发现可能会产生影响,这取决于给药的适应症和目的。
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引用次数: 8
Diagnostics as Prevention - A Rapid Testing-Based Strategy of Sex Workers against Sexual HIV Exposure. 诊断即预防——性工作者对抗性艾滋病毒暴露的快速检测策略。
Pub Date : 2018-05-05 eCollection Date: 2018-06-25 DOI: 10.1556/1886.2018.00007
Andreas Hahn, Rebecca Hinz, Thomas Meyer, Ulrike Loderstädt, Ottmar Herchenröder, Christian G Meyer, Norbert Georg Schwarz, Hagen Frickmann

Introduction: German sex workers have illegally established a prevention strategy, which consists of testing potential sexual partners with human immunodeficiency virus (HIV)-specific rapid diagnostic tests (RDTs) prior to engaging in unprotected sexual intercourse eventually performed in case of a negative test result. Based on a recently established modeling approach, the effectiveness of this strategy regarding the risk of HIV exposure was compared with protection provided by condom use.

Methods: Based on a literature search, the following assumptions were used for the calculations: an averaged 80% exposure risk reduction with a condom used during sexual intercourse, usage of a well-characterized 4th-generation HIV RDT, and a 10 day post-infection period without any measurable viral load in peripheral blood followed by a sero-conversion period of about 3 weeks with 12.3% test sensitivity (antigen-specific) and only afterwards 97.3% (antibody-specific) test sensitivity.

Results: In most constellations, the HIV exposure risk in case of RDT-based prevention was lower than with condom use. Conclusions: The RDT-based HIV exposure prevention as established by sex workers is effective in most situations. A notable weakness of the strategy is the RDTs' poor sensitivity in spite of a high transmission risk during the seroconversion stage.

导言:德国性工作者非法制定了一项预防战略,其中包括在进行无保护的性交之前对潜在的性伴侣进行人类免疫缺陷病毒(艾滋病毒)特异性快速诊断测试(RDTs),最终在测试结果为阴性的情况下进行。基于最近建立的建模方法,将这一策略在艾滋病毒暴露风险方面的有效性与使用避孕套提供的保护进行了比较。方法:基于文献检索,使用以下假设进行计算:性交时使用安全套平均降低80%的暴露风险,使用特征明确的第四代HIV RDT,感染后10天,外周血中没有任何可测量的病毒载量,随后的血清转换期约为3周,测试敏感性为12.3%(抗原特异性),仅在97.3%(抗体特异性)测试敏感性之后。结果:在大多数星座中,基于rdt预防的HIV暴露风险低于使用避孕套。结论:性工作者建立的基于rdt的HIV暴露预防在大多数情况下是有效的。该策略的一个显著弱点是,尽管在血清转化阶段传播风险很高,但rdt的敏感性较差。
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引用次数: 5
Peroral Low-Dose Toxoplasma gondii Infection of Human Microbiota-Associated Mice - A Subacute Ileitis Model to Unravel Pathogen-Host Interactions. 人类微生物群相关小鼠经口低剂量刚地弓形虫感染-亚急性回肠炎模型揭示病原体-宿主相互作用。
Pub Date : 2018-04-16 eCollection Date: 2018-06-25 DOI: 10.1556/1886.2018.00005
Markus M Heimesaat, Ulrike Escher, Anne Grunau, Ulrike Fiebiger, Stefan Bereswill

Within 1 week following high-dose Toxoplasma gondii infection, mice develop lethal necrotizing ileitis. However, data from a subacute T. gondii-induced ileitis model are scarce. Therefore, mice harboring a human gut microbiota were perorally infected with one cyst of T. gondii. Within 9 days post-infection, the intestinal microbiota composition shifted towards higher loads of commensal enterobacteria and enterococci. Following T. gondii infection, mice were clinically only mildly affected, whereas ≈60% of mice displayed fecal blood and mild-to-moderate ileal histopathological changes. Intestinal inflammation was further characterized by increased apoptotic intestinal epithelial cells, which were accompanied by elevated proliferating gut epithelial cell numbers. As compared to naive controls, infected mice displayed elevated numbers of intestinal T lymphocytes and regulatory T-cells and increased pro-inflammatory mediator secretion. Remarkably, T. gondii-induced apoptotic and pro-inflammatory immune responses were not restricted to the gut, but could also be observed in extra-intestinal compartments including kidney, liver, and lung. Strikingly, low-dose T. gondii infection resulted in increased serum levels of pro- and anti-inflammatory cytokines. In conclusion, the here presented subacute ileitis model following peroral low-dose T. gondii infection of humanized mice allows for detailed investigations of the molecular mechanism underlying the "ménage à trois" of pathogens, human gut microbiota, and immunity.

高剂量刚地弓形虫感染后1周内,小鼠出现致死性坏死性回肠炎。然而,亚急性弓形虫诱导的回肠炎模型的数据很少。因此,携带人类肠道菌群的小鼠经口感染了一个弓形虫囊肿。感染后9天内,肠道菌群组成向共生肠杆菌和肠球菌的高负荷转变。弓形虫感染后,小鼠临床仅轻度感染,而约60%的小鼠出现粪血和轻至中度回肠组织病理学改变。肠道炎症的进一步特征是肠上皮细胞凋亡增加,并伴有增生性肠上皮细胞数量增加。与未感染的对照组相比,感染小鼠的肠道T淋巴细胞和调节性T细胞数量增加,促炎介质分泌增加。值得注意的是,弓形虫诱导的凋亡和促炎免疫反应不仅局限于肠道,还可以在肠外隔间(包括肾、肝和肺)中观察到。引人注目的是,低剂量的弓形虫感染导致血清中促炎和抗炎细胞因子水平升高。总之,本文提出的经口低剂量弓形虫感染人源化小鼠的亚急性回肠炎模型,可以详细研究病原体、人类肠道微生物群和免疫的“交叉交叉”的分子机制。
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引用次数: 10
期刊
European Journal of Microbiology & Immunology
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