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Microbiota composition and inflammatory immune responses upon peroral application of the commercial competitive exclusion product Aviguard® to microbiota-depleted wildtype mice. 商业竞争排斥产品Aviguard®经口服应用于微生物群耗尽的野生型小鼠后,微生物群组成和炎症免疫反应。
Pub Date : 2020-07-27 DOI: 10.1556/1886.2020.00012
Markus M Heimesaat, Dennis Weschka, Sigri Kløve, Claudia Genger, Nina Biesemeier, Soraya Mousavi, Stefan Bereswill

Non-antibiotic feed additives including competitive exclusion products have been shown effective in reducing pathogen loads including multi-drug resistant strains from the vertebrate gut. In the present study we surveyed the intestinal bacterial colonization properties, potential macroscopic and microscopic inflammatory sequelae and immune responses upon peroral application of the commercial competitive exclusion product Aviguard® to wildtype mice in which the gut microbiota had been depleted by antibiotic pre-treatment. Until four weeks following Aviguard® challenge, bacterial strains abundant in the probiotic suspension stably established within the murine intestines. Aviguard® application did neither induce any clinical signs nor gross macroscopic intestinal inflammatory sequelae, which also held true when assessing apoptotic and proliferative cell responses in colonic epithelia until day 28 post-challenge. Whereas numbers of colonic innate immune cell subsets such as macrophages and monocytes remained unaffected, peroral Aviguard® application to microbiota depleted mice was accompanied by decreases in colonic mucosal counts of adaptive immune cells such as T and B lymphocytes. In conclusion, peroral Aviguard® application results i.) in effective intestinal colonization within microbiota depleted mice, ii.) neither in macroscopic nor in microscopic inflammatory sequelae and iii.) in lower colonic mucosal T and B cell responses.

包括竞争性排除产品在内的非抗生素饲料添加剂已被证明可有效减少脊椎动物肠道中的病原体负荷,包括多重耐药菌株。在本研究中,我们调查了肠道细菌定植特性、潜在的宏观和微观炎症后遗症以及对经抗生素预处理后肠道微生物群耗尽的野生型小鼠口服竞争排斥产品Aviguard®后的免疫反应。直到Aviguard®激发后四周,益生菌悬浮液中丰富的细菌菌株在小鼠肠道内稳定建立。Aviguard®应用既没有引起任何临床症状,也没有引起肉眼可见的肠道炎症后遗症,这在评估结肠上皮细胞凋亡和增殖反应时也是如此,直到28天后。尽管结肠先天免疫细胞亚群(如巨噬细胞和单核细胞)的数量不受影响,但经口应用Aviguard®对微生物群减少的小鼠,结肠粘膜适应性免疫细胞(如T淋巴细胞和B淋巴细胞)计数减少。综上所述,经口应用Aviguard®的结果是:(1)在微生物群枯竭的小鼠中有效的肠道定植,(2)既不影响宏观也不影响微观的炎症后遗症,(3)下结肠粘膜T细胞和B细胞反应。
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引用次数: 1
Toxoplasma gondii infection and multiple sclerosis: An age- and a gender-matched case-control seroprevalence study. 刚地弓形虫感染与多发性硬化症:年龄和性别匹配的病例对照血清阳性率研究。
Pub Date : 2020-07-02 DOI: 10.1556/1886.2019.00020
Edna Madai Méndez-Hernández, Jesús Hernández-Tinoco, José Manuel Salas-Pacheco, Luis Francisco Sánchez-Anguiano, Oscar Arias-Carrión, Ada Agustina Sandoval-Carrillo, Francisco Xavier Castellanos-Juárez, Luis Ángel Ruano-Calderón, Cosme Alvarado-Esquivel

The link between Toxoplasma gondii infection and multiple sclerosis remains controversial. In the present study, we aimed to determine the association between T. gondii seropositivity and multiple sclerosis. Using an age- and gender-matched case-control study, we studied 45 patients who had multiple sclerosis attended in two public hospitals and 225 control subjects without this disease and other neurological disorders in Durango City, Mexico. Serum samples of cases and controls were analyzed for detection of anti-Toxoplasma IgG using a commercially available enzyme-linked immunoassay. One (2.22%) of the 45 patients with multiple sclerosis, and 15 (6.67%) of the 225 control subjects without this disease were seropositive for anti-T. gondii IgG antibodies. No statistically significant difference (OR = 0.31; 95% CI: 0.04-2.47; P = 0.48) in seroprevalence of anti-T. gondii IgG antibodies between cases and controls was found. The frequency of T. gondii seropositivity did not vary among cases and controls about sex or age groups. Results of this study do not support an association between seropositivity to T. gondii and multiple sclerosis. However, additional research with larger sample sizes to confirm this lack of association should be conducted.

弓形虫感染与多发性硬化症之间的联系仍然存在争议。在本研究中,我们旨在确定弓形虫血清阳性与多发性硬化症之间的关系。采用年龄和性别匹配的病例对照研究,我们研究了45名在墨西哥杜兰戈市两家公立医院就诊的多发性硬化症患者和225名没有这种疾病和其他神经系统疾病的对照受试者。对病例和对照组的血清样本进行分析,使用市售的酶联免疫分析法检测抗弓形虫IgG。45例多发性硬化症患者血清t抗体阳性1例(2.22%),225例非多发性硬化症对照患者血清t抗体阳性15例(6.67%)。刚地IgG抗体。差异无统计学意义(OR = 0.31;95% ci: 0.04-2.47;P = 0.48)。病例与对照组间均检测到弓形虫IgG抗体。弓形虫血清阳性的频率在病例和对照组之间没有性别或年龄组的差异。本研究结果不支持弓形虫血清阳性与多发性硬化症之间的联系。然而,应该进行更多的研究,样本量更大,以证实这种缺乏联系。
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引用次数: 6
Acute neonatal Listeria monocytogenes infection causes long-term, organ-specific changes in immune cell subset composition. 急性新生儿单核细胞增生李斯特菌感染引起免疫细胞亚群组成的长期器官特异性变化。
Pub Date : 2020-06-19 DOI: 10.1556/1886.2020.00007
Mangge Zou, Juhao Yang, Carolin Wiechers, Jochen Huehn

Listeria monocytogenes (Lm) is a food-borne pathogen with a high chance of infecting neonates, pregnant women, elderly and immunocompromised individuals. Lm infection in neonates can cause neonatal meningitis and sepsis with a high risk of severe neurological and developmental sequelae and high mortality rates. However, whether an acute neonatal Lm infection causes long-term effects on the immune system persisting until adulthood has not been fully elucidated. Here, we established a neonatal Lm infection model and monitored the composition of major immune cell subsets at defined time points post infection (p.i.) in secondary lymphoid organs and the intestine. Twelve weeks p.i., the CD8+ T cell population was decreased in colon and mesenteric lymph nodes (mLNs) with an opposing increase in the spleen. In the colon, we observed an accumulation of CD4+ and CD8+ effector/memory T cells with an increase of T-bet+ T helper 1 (Th1) cells. In addition, 12 weeks p.i. an altered composition of innate lymphoid cell (ILC) and dendritic cell (DC) subsets was still observed in colon and mLNs, respectively. Together, these findings highlight organ-specific long-term consequences of an acute neonatal Lm infection on both the adaptive and innate immune system.

单核细胞增生李斯特菌是一种食源性病原体,极易感染新生儿、孕妇、老年人和免疫功能低下的个体。新生儿感染Lm可导致新生儿脑膜炎和败血症,具有严重神经和发育后遗症的高风险和高死亡率。然而,急性新生儿Lm感染是否会对免疫系统产生持续到成年的长期影响还没有完全阐明。在这里,我们建立了一个新生儿Lm感染模型,并在继代淋巴器官和肠道感染后的特定时间点监测主要免疫细胞亚群的组成。12周后,结肠和肠系膜淋巴结(mLNs)的CD8+ T细胞数量减少,脾脏的CD8+ T细胞数量相反增加。在结肠中,我们观察到CD4+和CD8+效应/记忆T细胞的积累,T-bet+ T辅助1 (Th1)细胞的增加。此外,12周后,结肠和mln中仍分别观察到先天淋巴样细胞(ILC)和树突状细胞(DC)亚群组成的改变。总之,这些发现强调了急性新生儿Lm感染对适应性和先天免疫系统的器官特异性长期后果。
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引用次数: 5
Relevance of anaerobic bacteremia in adult patients: A never-ending story? 成人患者厌氧菌血症的相关性:一个永无止境的故事?
Pub Date : 2020-06-05 DOI: 10.1556/1886.2020.00009
Márió Gajdács, Edit Urbán

Obligate anaerobic bacteria are considered important constituents of the microbiota of humans; in addition, they are also important etiological agents in some focal or invasive infections and bacteremia with a high level of mortality. Conflicting data have accumulated over the last decades regarding the extent in which these pathogens play an intrinsic role in bloodstream infections. Clinical characteristics of anaerobic bloodstream infections do not differ from bacteremia caused by other pathogens, but due to their longer generation time and rigorous growth requirements, it usually takes longer to establish the etiological diagnosis. The introduction of matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS) has represented a technological revolution in microbiological diagnostics, which has allowed for the fast, accurate and reliable identification of anaerobic bacteria at a low sample cost. The purpose of this review article is to summarize the currently available literature data on the prevalence of anaerobic bacteremia in adults for physicians and clinical microbiologists and to shed some light on the complexity of this topic nowadays.

专性厌氧细菌被认为是人类微生物群的重要组成部分;此外,它们也是一些具有高死亡率的局灶性或侵袭性感染和菌血症的重要病原体。在过去的几十年里,关于这些病原体在血液感染中发挥内在作用的程度,积累了相互矛盾的数据。无氧血流感染的临床特征与其他病原体引起的菌血症没有区别,但由于其产生时间较长,生长要求严格,通常需要较长的时间才能建立病因诊断。基质辅助激光解吸-电离飞行时间质谱(MALDI-TOF MS)的引入代表了微生物诊断的技术革命,它可以以低样品成本快速,准确和可靠地鉴定厌氧细菌。这篇综述文章的目的是为医生和临床微生物学家总结目前可获得的关于成人厌氧菌血症患病率的文献数据,并阐明当今这一主题的复杂性。
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引用次数: 39
The incidence of anaerobic bacteria in adult patients with chronic sinusitis: A prospective, single-centre microbiological study. 成人慢性鼻窦炎患者厌氧菌的发病率:一项前瞻性、单中心微生物学研究。
Pub Date : 2020-06-05 DOI: 10.1556/1886.2020.00010
Edit Urbán, Márió Gajdács, Attila Torkos

Introduction: Chronic sinusitis caused by anaerobes is a particular concern clinically, because many of the complications are associated with infections caused by these organisms. The aim of this study was to evaluate the incidence of anaerobic bacteria in chronic sinusitis in adults as a part of a prospective microbiological study.

Materials and methods: Over a one-year period, aspirations of maxillary sinus secretions and/or ethmoid cavities were derived in n = 79 adult patients with chronic sinusitis by endoscopy in a tertiary-care teaching hospital in Hungary. The qualitative and quantitative compositions of the total cultivable aerobic and anaerobic bacterial and fungal flora cultured on the samples were compared. Correct anaerobic species level identifications were carried out according to standard methods.

Results: Bacteria were recovered for all of the 79 aspirates and the numbers of the significant cultured isolates (with colony forming units ≥103) were between 1 and 10. A total of 206 isolates, 106 anaerobic and 100 aerobic or facultative-anaerobic strains were isolated. The most common aerobic bacteria were Streptococcus pneumoniae (n = 40), Haemophilus influenzae (n = 29), Moraxella catarrhalis (n = 6), Staphylococcus aureus (n = 7) and Streptococcus pyogenes (n = 6). The anaerobic bacteria included black-pigmented Prevotella spp. and Porphyromonas spp. (n = 27), Actinomyces spp. (n = 13), Gram-positive anaerobic cocci (n = 16), Fusobacterium spp. (n = 19) and Cutibacterium acnes (n = 8).

Conclusions: This study illustrates the microbial dynamics in which anaerobic and aerobic bacteria prevail and highlights the importance of obtaining cultures from patients with chronic sinusitis for guidance in selection of proper antimicrobial therapy.

由厌氧菌引起的慢性鼻窦炎是临床上特别关注的问题,因为许多并发症与这些微生物引起的感染有关。本研究的目的是评估成人慢性鼻窦炎中厌氧菌的发生率,作为前瞻性微生物学研究的一部分。材料和方法:在一年的时间里,在匈牙利的一家三级护理教学医院,通过内窥镜检查,对n = 79名慢性鼻窦炎成年患者进行了上颌窦分泌物和/或筛腔的检查。比较了样品上培养的总可培养的好氧和厌氧细菌和真菌菌群的定性和定量组成。按照标准方法进行正确的厌氧菌种水平鉴定。结果:79次抽吸均检出细菌,培养的显著菌株(菌落形成单位≥103)数量在1 ~ 10个之间。共分离到206株,厌氧106株,好氧或兼性厌氧100株。最常见的需氧细菌为肺炎链球菌(40株)、流感嗜血杆菌(29株)、卡他莫拉菌(6株)、金黄色葡萄球菌(7株)和化脓性链球菌(6株),厌氧菌包括黑色普雷沃氏菌和卟啉单胞菌(27株)、放线菌(13株)、革兰氏阳性厌氧球菌(16株)、梭杆菌(19株)和痤疮表皮杆菌(8株)。本研究阐明了微生物动力学,其中厌氧和好氧细菌占主导地位,并强调了从慢性鼻窦炎患者获得培养的重要性,以指导选择适当的抗菌治疗。
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引用次数: 8
Review: The risk of contracting anthrax from spore-contaminated soil - A military medical perspective. 综述:从孢子污染土壤感染炭疽的风险——军事医学视角。
Pub Date : 2020-06-05 DOI: 10.1556/1886.2020.00008
Ernst-Jürgen Finke, Wolfgang Beyer, Ulrike Loderstädt, Hagen Frickmann

Anthrax is an infectious disease of relevance for military forces. Although spores of Bacillus anthracis obiquitously occur in soil, reports on soil-borne transmission to humans are scarce. In this narrative review, the potential of soil-borne transmission of anthrax to humans is discussed based on pathogen-specific characteristics and reports on anthrax in the course of several centuries of warfare. In theory, anthrax foci can pose a potential risk of infection to animals and humans if sufficient amounts of virulent spores are present in the soil even after an extended period of time. In praxis, however, transmissions are usually due to contacts with animal products and reported events of soil-based transmissions are scarce. In the history of warfare, even in the trenches of World War I, reported anthrax cases due to soil-contaminated wounds are virtually absent. Both the perspectives and the experience of the Western hemisphere and of former Soviet Republics are presented. Based on the accessible data as provided in the review, the transmission risk of anthrax by infections of wounds due to spore-contaminated soil is considered as very low under the most circumstance. Active historic anthrax foci may, however, still pose a risk to the health of deployed soldiers.

炭疽是一种与军队有关的传染病。虽然炭疽芽孢杆菌孢子在土壤中明显存在,但关于通过土壤传播给人类的报道很少。在这篇叙述性综述中,基于病原体特异性特征和几个世纪战争过程中关于炭疽的报道,讨论了炭疽土媒传播给人类的可能性。理论上,如果土壤中存在足够数量的毒孢子,即使在很长一段时间后,炭疽疫源地也可能对动物和人类造成感染的潜在风险。然而,在实践中,传播通常是由于与动物产品接触,报告的基于土壤的传播事件很少。在战战史上,甚至在第一次世界大战的战壕中,几乎没有因土壤污染伤口而报告的炭疽病例。本书介绍了西半球和前苏联加盟共和国的观点和经验。根据审查中提供的可获得的数据,在大多数情况下,孢子污染土壤导致伤口感染的炭疽传播风险很低。然而,活跃的历史炭疽疫源地仍可能对部署的士兵的健康构成威胁。
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引用次数: 0
The conundrum of colonization resistance against Campylobacter reloaded: The gut microbota composition in conventional mice does not prevent from Campylobacter coli infection. 对弯曲杆菌的定植抗性难题:常规小鼠的肠道微生物组成不能阻止大肠弯曲杆菌的感染。
Pub Date : 2020-05-01 DOI: 10.1556/1886.2020.00004
Claudia Genger, Sigri Kløve, Soraya Mousavi, Stefan Bereswill, Markus M Heimesaat

The physiological colonization resistance exerted by the murine gut microbiota prevents conventional mice from Campylobacter jejuni infection. In the present study we addressed whether this also held true for Campylobacter coli. Following peroral application, C. coli as opposed to C. jejuni could stably establish within the gastrointestinal tract of conventionally colonized mice until 3 weeks post-challenge. Neither before nor after either Campylobacter application any changes in the gut microbiota composition could be observed. C. coli, but not C. jejuni challenge was associated with pronounced regenerative, but not apoptotic responses in colonic epithelia. At day 21 following C. coli versus C. jejuni application mice exhibited higher numbers of adaptive immune cells including T-lymphocytes and regulatory T-cells in the colonic mucosa and lamina propria that were accompanied by higher large intestinal interferon-γ (IFN-γ) concentrations in the former versus the latter but comparable to naive levels. Campylobacter application resulted in decreased splenic IFN-γ, tumor necrosis factor-α (TNF-α), and IL-6 concentrations, whereas IL-12p70 secretion was increased in the spleens at day 21 following C. coli application only. In either Campylobacter cohort decreased IL-10 concentrations could be measured in splenic and serum samples. In conclusion, the commensal gut microbiota prevents mice from C. jejuni, but not C. coli infection.

小鼠肠道菌群的生理定植抗性使常规小鼠免受空肠弯曲杆菌感染。在目前的研究中,我们探讨了这是否也适用于大肠弯曲杆菌。经口施用后,大肠杆菌可在常规定植的小鼠胃肠道内稳定建立,直至攻毒后3周。在使用弯曲杆菌之前和之后,肠道菌群组成都没有任何变化。大肠杆菌,而非空肠梭菌的攻击与结肠上皮细胞明显的再生反应有关,而与凋亡反应无关。在大肠杆菌与空肠杆菌应用后的第21天,小鼠在结肠黏膜和固有层中表现出更高数量的适应性免疫细胞,包括t淋巴细胞和调节性t细胞,并伴随着大肠干扰素-γ (IFN-γ)浓度高于后者,但与幼稚水平相当。弯曲杆菌导致脾脏IFN-γ、肿瘤坏死因子-α (TNF-α)和IL-6浓度降低,而大肠杆菌仅在第21天导致脾脏IL-12p70分泌增加。在任何弯曲杆菌组中,脾脏和血清样本中IL-10浓度均下降。综上所述,肠道共生菌群可预防小鼠空肠梭菌感染,但不能预防大肠杆菌感染。
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引用次数: 7
A 10-year single-center experience on Stenotrophomonas maltophilia resistotyping in Szeged, Hungary. 匈牙利塞格德嗜麦芽寡养单胞菌耐药性分型的10年单中心经验。
Pub Date : 2020-04-23 DOI: 10.1556/1886.2020.00006
Márió Gajdács, Edit Urbán

Stenotrophomonas maltophilia is an aerobic, oxidase-negative and catalase-positive bacillus. S. maltophilia is a recognized opportunistic pathogen. Due to the advancements in invasive medical procedures, organ transplantation and chemotherapy of malignant illnesses, the relevance of this pathogen increased significantly. The therapy of S. maltophilia infections is challenging, as these bacteria show intrinsic resistance to multiple classes of antibiotics, the first-choice drug is sulfamethoxazole/trimethoprim. Our aim was to assess the epidemiology of S. maltophilia from various clinical samples and the characterization of resistance-levels and resistotyping of these samples over a long surveillance period. The study included S. maltophilia bacterial isolates from blood culture samples, respiratory samples and urine samples and the data for the samples, received between January 2008 until December 2017, a total of 817 S. maltophilia isolates were identified (respiratory samples n = 579, 70.9%, blood culture samples n = 175, 21.4% and urine samples n = 63, 7.7%). Levofloxacin and colistin-susceptibility rates were the highest (92.2%; n = 753), followed by tigecycline (90.5%, n = 739), the first-line agent sulfamethoxazole/trimethoprim (87.4%, n = 714), while phenotypic resistance rate was highest for amikacin (72.5% of isolates were resistant, n = 592). The clinical problem of sulfamethoxazole/trimethoprim-resistance is a complex issue, because there is no guideline available for the therapy of these infections.

嗜麦芽窄养单胞菌是一种需氧、氧化酶阴性和过氧化氢酶阳性的芽孢杆菌。嗜麦芽葡萄球菌是公认的条件致病菌。由于侵入性医疗程序、器官移植和恶性疾病化疗的进步,这种病原体的相关性显著增加。嗜麦芽葡萄球菌感染的治疗具有挑战性,因为这些细菌对多种抗生素表现出内在耐药性,首选药物是磺胺甲恶唑/甲氧苄啶。我们的目的是评估来自不同临床样本的嗜麦芽链球菌的流行病学,以及这些样本在长期监测期间的耐药水平和耐药分型特征。本研究收集了2008年1月至2017年12月期间从血培养样本、呼吸样本和尿液样本中分离出的嗜麦芽葡萄球菌,共鉴定出嗜麦芽葡萄球菌817株(呼吸样本n = 579,占70.9%,血培养样本n = 175,占21.4%,尿液样本n = 63,占7.7%)。左氧氟沙星和粘菌素敏感性最高(92.2%;N = 753),其次是替加环素(90.5%,N = 739),一线药物磺胺甲恶唑/甲氧苄啶(87.4%,N = 714),而阿米卡星的表型耐药率最高(72.5%,N = 592)。磺胺甲恶唑/甲氧苄啶耐药的临床问题是一个复杂的问题,因为目前尚无治疗这些感染的指导方针。
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引用次数: 11
Influence of Immune Status on the Airborne Colonization of Piglets with Methicillin-Resistant Staphylococcus aureus (MRSA) Clonal Complex (CC) 398. 免疫状态对耐甲氧西林金黄色葡萄球菌(MRSA)克隆复合体(CC) 398在仔猪空气定植的影响
Pub Date : 2020-04-07 DOI: 10.1556/1886.2019.00024
Kerstin Rosen, Friederike Ebner, Stefanie Schmidt, Susanne Hartmann, Roswitha Merle, Anika Friese, Uwe Roesler

Colonized vertebrates including humans and pigs are to date the main reservoirs of livestock-associated Methicillin-resistant Staphylococcus aureus (LA-MRSA). Currently, the mechanisms underlying colonization of pigs are not fully understood. We investigated the influence of piglet pre-immune status on airborne MRSA colonization. Three groups of MRSA-negative piglets were primed and exposed to airborne LA-MRSA (104 colony forming units (cfu)/m3) in an aerosol chamber for 24 h. One group was treated intramuscularly with dexamethasone (1 mg/kg body weight) to imitate weaning stress. The second group was exposed to bacterial endotoxin containing MRSA aerosol. Both conditions play a role in the development of multifactorial diseases and may promote MRSA colonization success. The third group served as control. The piglets' MRSA status was monitored for 21 days via swab samples. At necropsy, specific tissues and organs were analyzed. Blood was collected to examine specific immunological parameters. The duration of MRSA colonization was not extended in both treated groups compared to the control group, indicating the two immune-status influencing factors do not promote MRSA colonization. Blood sample analysis confirmed a mild dexamethasone-induced immune suppression and typical endotoxin-related changes in peripheral blood. Of note, the low-dose dexamethasone treatment showed a trend of increased MRSA clearance.

迄今为止,包括人类和猪在内的定殖脊椎动物是家畜相关的耐甲氧西林金黄色葡萄球菌(LA-MRSA)的主要宿主。目前,猪的定植机制尚不完全清楚。我们研究了仔猪免疫前状态对空气中MRSA定植的影响。将3组mrsa阴性仔猪置于气溶胶室中暴露于空气传播的LA-MRSA(104菌落形成单位(cfu)/m3)中24 h。其中一组采用地塞米松(1 mg/kg体重)肌肉注射模拟断奶应激。第二组暴露于含有细菌内毒素的MRSA气雾剂中。这两种情况都在多因子疾病的发展中发挥作用,并可能促进MRSA定植的成功。第三组作为对照组。通过拭子样本监测仔猪的MRSA状态21天。尸检时,对特定组织和器官进行分析。采集血液检查特定的免疫参数。与对照组相比,两个治疗组的MRSA定殖时间均未延长,表明两种免疫状态影响因素并未促进MRSA定殖。血液样本分析证实轻度地塞米松诱导的免疫抑制和典型的外周血内毒素相关变化。值得注意的是,低剂量地塞米松治疗有增加MRSA清除率的趋势。
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引用次数: 4
No Genotoxicity Is Detectable for Escherichia coli Strain Nissle 1917 by Standard In Vitro and In Vivo Tests. 通过标准体外和体内试验,大肠杆菌尼索尔1917株未检测到遗传毒性。
Pub Date : 2020-03-17 eCollection Date: 2020-04-07 DOI: 10.1556/1886.2019.00025
Silke Dubbert, Birgit Klinkert, Michael Schimiczek, Trudy M Wassenaar, Rudolf von Bünau

Probiotic Escherichia coli strain Nissle 1917 (EcN) has a long history of safe use. However, the recently discovered presence of a pks locus in its genome presumably producing colibactin has questioned its safety, as colibactin has been implicated in genotoxicity. Here, we assess the genotoxic potential of EcN. Metabolic products were tested in vitro by the Ames test, a mutagenicity assay developed to detect point mutation-inducing activity. Live EcN were tested by an adapted Ames test. Neither the standard nor the adapted Ames test resulted in increased numbers of revertant colonies, indicating that EcN metabolites or viable cells lacked mutagenic activity. The in vivo Mammalian Alkaline Comet Assay (the gold standard for detecting DNA-strand breaks) was used to determine potentially induced DNA-strand breaks in cells of the gastro-intestinal tract of rats orally administered with viable EcN. Bacteria were given at 109-1011 colony forming units (CFU) per animal by oral gavage on 2 consecutive days and daily for a period of 28 days to 5 rats per group. No significant differences compared to negative controls were found. These results demonstrate that EcN does not induce DNA-strand breaks and does not have any detectable genotoxic potential in the test animals.

益生菌大肠杆菌Nissle 1917 (EcN)具有悠久的安全使用历史。然而,最近在其基因组中发现了可能产生大肠杆菌蛋白的pks位点,这对其安全性提出了质疑,因为大肠杆菌蛋白与遗传毒性有关。在这里,我们评估EcN的遗传毒性潜力。代谢产物在体外通过Ames试验进行测试,这是一种用于检测点诱变诱导活性的诱变性试验。采用改良的Ames试验对活体EcN进行检测。标准试验和改良的Ames试验均未导致逆转菌落数量增加,这表明EcN代谢物或活细胞缺乏致突变活性。采用哺乳动物碱性彗星法(检测dna链断裂的金标准)测定口服活EcN的大鼠胃肠道细胞中可能诱导的dna链断裂。以每只动物109 ~ 1011菌落形成单位(CFU)的剂量连续灌胃2天,每组5只,连续28 d。与阴性对照相比,无显著差异。这些结果表明,EcN不会诱导dna链断裂,并且在试验动物中没有任何可检测到的基因毒性潜力。
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引用次数: 13
期刊
European Journal of Microbiology & Immunology
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