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Comparative analysis of antibiotic resistance and biofilm formation in Enterococcus spp. across One Health domains. 同一健康领域肠球菌抗生素耐药性和生物膜形成的比较分析。
Pub Date : 2025-04-25 eCollection Date: 2025-01-01 DOI: 10.1093/femsmc/xtaf005
Vanessa Silva, Catarina Freitas, Jessica Ribeiro, Gilberto Igrejas, Patricia Poeta

The rise of antibiotic-resistant bacteria is a critical issue across various ecological interfaces, highlighting the need for a One Health approach. Enterococcus spp., known for their ability to acquire and disseminate resistance, serve as an excellent model due to their presence in diverse hosts and environments. This study investigates antimicrobial resistance, biofilm formation capacity, and the efficacy of antibiotics on biofilm biomass reduction in isolates from multiple sources. A total of 197 Enterococcus isolates were used. Antimicrobial resistance was determined using the Kirby-Bauer disc diffusion method, and minimum inhibitory concentrations were tested against vancomycin, tetracycline, and ampicillin. Biofilm formation capacity was assessed, and 10 biofilm-formers were subjected to minimum biofilm inhibitory concentration (MBIC) tests to evaluate biofilm biomass reduction. The results showed high resistance rates to erythromycin (84.5%), ciprofloxacin (59.4%), and tetracycline (44.4%), with moderate resistance to ampicillin (36.2%), chloramphenicol (28%), and vancomycin (24.7%). Biofilm formation was observed in 65% of the isolates, with Enterococcus hirae producing the most biofilm biomass. Vancomycin and ampicillin were more effective in reducing biofilm biomass than tetracycline. Ampicillin-resistant isolates produced more biofilm, suggesting a link between resistance and biofilm formation. This study highlights the complexity of antibiotic-resistant Enterococcus spp. and their biofilms, emphasizing the need for research on One Health.

耐抗生素细菌的增加是跨各种生态界面的一个关键问题,突出了一个健康方法的必要性。肠球菌以其获得和传播耐药性的能力而闻名,由于它们存在于不同的宿主和环境中,因此可以作为一个很好的模型。本研究研究了来自多个来源的菌株的抗微生物药物耐药性、生物膜形成能力以及抗生素对生物膜生物量减少的影响。共分离肠球菌197株。采用Kirby-Bauer圆盘扩散法测定其耐药性,并测定其对万古霉素、四环素和氨苄西林的最低抑菌浓度。对生物膜形成能力进行了评估,并对10个生物成膜体进行了最低生物膜抑制浓度(MBIC)测试,以评估生物膜生物量的减少。结果显示,对红霉素(84.5%)、环丙沙星(59.4%)、四环素(44.4%)的耐药率较高,对氨苄西林(36.2%)、氯霉素(28%)、万古霉素(24.7%)的耐药率中等。在65%的分离株中观察到生物膜的形成,其中以产肠球菌的生物膜生物量最多。万古霉素和氨苄西林在减少生物膜生物量方面比四环素更有效。耐氨苄青霉素的分离株产生更多的生物膜,表明耐药性与生物膜形成之间存在联系。本研究突出了耐抗生素肠球菌及其生物膜的复杂性,强调了对“同一个健康”进行研究的必要性。
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引用次数: 0
Psychrotrophic Antarctic marine bacteria as potential reservoirs for novel antimicrobial genes. 南极海洋嗜冷细菌作为新型抗菌基因的潜在宿主。
Pub Date : 2025-04-15 eCollection Date: 2025-01-01 DOI: 10.1093/femsmc/xtaf004
Kudzai Hwengwere, Grant G January, Kerry L Howell, Lloyd S Peck, Mathew Upton, Melody S Clark

Antarctica is a very cold, isolated continent surrounded by frozen seas, yet these extreme environmental conditions have not restricted life and diversity in the sea. The marine environment is seasonally highly productive and harbours diverse and abundant communities of organisms, with many endemic species occurring nowhere else in the world. Such communities and their associated microbiomes are increasingly recognized as an unexplored source of novel antimicrobial products. Hence, the major aim of this study was to examine the antimicrobial potential of bacteria cultured from eight Antarctic marine invertebrate species, while gathering data on Antarctic microbial thermal and salinity tolerances. All cultured bacterial species (n = 34) were related to known psychrotrophs, with thermal tolerances that far exceeded those of their invertebrate hosts. Of note, two strains of Psychrobacter and Pseudomonas produced antagonistic activity towards epidemic methicillin-resistant Staphylococcus aureus, Micrococcus luteus, and Candida albicans in preliminary simultaneous antagonism screens. Draft whole genome sequence analysis revealed the presence of 13 biosynthetic gene clusters; including those with potential to produce betalactones, post-translationally modified peptide products, and arylpropynes. These results emphasize the need for more extensive and systematic surveys to identify novel biomolecules from Antarctic marine bacteria that may be exploited for societal gain.

南极洲是一个被冰冻的海洋包围的非常寒冷、孤立的大陆,然而这些极端的环境条件并没有限制海洋中的生命和多样性。海洋环境是季节性的高产环境,拥有多样化和丰富的生物群落,其中许多特有物种是世界上其他地方所没有的。这些微生物群落及其相关微生物组越来越被认为是一种尚未开发的新型抗菌产品来源。因此,本研究的主要目的是研究从8种南极海洋无脊椎动物中培养的细菌的抗菌潜力,同时收集南极微生物耐高温和耐盐性的数据。所有培养的细菌种类(n = 34)都与已知的嗜冷菌有关,它们的耐热性远远超过它们的无脊椎宿主。值得注意的是,在初步的同时拮抗筛选中,两株冷杆菌和假单胞菌对流行的耐甲氧西林金黄色葡萄球菌、黄体微球菌和白色念珠菌产生了拮抗活性。草图全基因组序列分析显示存在13个生物合成基因簇;包括具有生产β内酯、翻译后修饰肽产品和芳基丙炔的潜力的那些。这些结果强调需要进行更广泛和系统的调查,以从南极海洋细菌中识别可能用于社会利益的新型生物分子。
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引用次数: 0
The importance of translational research in the study of ocular toxoplasmosis: insights from the 17th International Congress on Toxoplasmosis 2024. 翻译研究在眼弓形虫病研究中的重要性:来自第17届2024年国际弓形虫病大会的见解。
Pub Date : 2025-03-03 eCollection Date: 2025-01-01 DOI: 10.1093/femsmc/xtaf003
Alejandra de-la-Torre, Germán Mejía-Salgado, Gereon Schares

Toxoplasmosis is a parasitic infection with significant implications for human health, particularly in its ocular form, which can lead to severe visual impairment. While both basic and clinical research have made considerable strides in understanding the biology and treatment of this parasite, challenges remain. Recent advancements in diagnostics, mainly through multimodal imaging, have improved the identification of active disease and predicting outcomes. Experimental therapies are also emerging, offering new hope for more effective treatments. However, the most critical insight from recent research, particularly emphasized at the 17th International Congress on Toxoplasmosis, is the necessity of a collaborative approach. Integrating basic and clinical research is essential for translating molecular and pathophysiological findings into effective clinical practices. This synergy is crucial for advancing treatment strategies and improving patient outcomes in ocular toxoplasmosis.

弓形虫病是一种寄生虫感染,对人类健康具有重大影响,特别是其眼部形式,可导致严重的视力损害。虽然基础和临床研究在了解这种寄生虫的生物学和治疗方面取得了相当大的进展,但挑战仍然存在。最近在诊断方面的进展,主要是通过多模态成像,改进了活动性疾病的识别和预测结果。实验性疗法也在不断涌现,为更有效的治疗提供了新的希望。然而,从最近的研究中,特别是在第17届国际弓形虫病大会上强调的最关键的见解是合作方法的必要性。整合基础和临床研究对于将分子和病理生理发现转化为有效的临床实践至关重要。这种协同作用对于推进治疗策略和改善眼弓形虫病患者的预后至关重要。
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引用次数: 0
Age and ocular toxoplasmosis: a narrative review. 年龄与眼弓形虫病:叙述性综述。
Pub Date : 2025-02-26 eCollection Date: 2025-01-01 DOI: 10.1093/femsmc/xtaf002
Alejandra de-la-Torre, Germán Mejía-Salgado, Armin Taghavi Eraghi, Uwe Pleyer

Toxoplasma gondii is an extremely "successful" opportunistic parasite that infects most warm-blooded animals, including humans. While the infection is generally largely asymptomatic, the infection of the eye presenting as ocular toxoplasmosis (OT) is a potentially blinding consequence. OT remains the most common cause of infectious retinochoroiditis and places a considerable socio-economic burden on societies, particularly in developing countries. Age is one of several factors influencing the clinical presentation and outcomes of OT. Older patients often exhibit more severe disease manifestations, larger retinal lesions, and poorer visual outcomes compared to younger individuals. This disparity is attributed to immunosenescence, the age-related decline in immune function, which impairs the body's ability to control the infection effectively. Consequently, older individuals are at a higher risk of severe complications and recurrent episodes of inflammation. Understanding the interplay between age and immune response is essential for developing targeted treatment strategies and improving patient outcomes in OT.

刚地弓形虫是一种极其“成功”的机会性寄生虫,可以感染大多数温血动物,包括人类。虽然感染通常在很大程度上是无症状的,但眼睛感染表现为眼弓形虫病(OT)是一种潜在的致盲后果。OT仍然是感染性视网膜脉络膜炎的最常见原因,并给社会,特别是发展中国家造成相当大的社会经济负担。年龄是影响OT临床表现和预后的几个因素之一。与年轻人相比,老年患者往往表现出更严重的疾病表现,更大的视网膜病变和更差的视力结果。这种差异归因于免疫衰老,即与年龄相关的免疫功能下降,损害了身体有效控制感染的能力。因此,老年人患严重并发症和反复发作炎症的风险更高。了解年龄和免疫反应之间的相互作用对于制定有针对性的治疗策略和改善OT患者的预后至关重要。
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引用次数: 0
Influenza a virus subtype H9N2 infection induces respiratory microbiota dysbiosis in chickens via type-I interferon-mediated mechanisms. 甲型流感病毒亚型H9N2感染通过i型干扰素介导的机制诱导鸡呼吸道微生物群失调。
Pub Date : 2025-02-03 eCollection Date: 2025-01-01 DOI: 10.1093/femsmc/xtaf001
Samson Oladokun, Mohammadali Alizadeh, Amirul I Mallick, Fatemeh Fazel, Janan Shoja Doost, Katherine Blake, Myles St Denis, Sugandha Raj, Shayan Sharif

Avian influenza virus (AIV) poses significant threats to poultry and human health. This study investigates the impact of H9N2 AIV infection on the respiratory microbiota of chickens using 16S rRNA gene sequencing. Total 48 one-day-old specific pathogen-free chickens were assigned to six groups: a control and five post-infection groups (days 1, 3, 5, 7, and 9). After a 15-day microbiota stabilization period, the infected chickens received a viral inoculum (107 TCID50/ml) via ocular, intra-nasal, and intra-tracheal routes. Tracheal and broncho-alveolar lavage samples were analyzed. Significant reductions in microbiota diversity were observed on days 5, 7, and 9 post-infection, compared to d0 controls. Permutational Multivariate Analysis of Variance confirmed significant beta diversity differences (P = 0.001) between infected and uninfected groups. The microbial shifts from d5 to d9 were marked by increased Proteobacteria, decreased Actinobacteria and Firmicutes, and a rise in Dickeya. Elevated type-I interferon (IFN-β) and viperin gene expression at d5 coincided with reduced microbiota diversity, highlighting the respiratory microbiota's role in modulating host responses to AIV H9N2 infection and suggesting potential biomarkers for respiratory dysbiosis.

禽流感病毒(AIV)对家禽和人类健康构成重大威胁。本研究采用 16S rRNA 基因测序法研究 H9N2 AIV 感染对鸡呼吸道微生物群的影响。总共 48 只一天龄无特定病原体的鸡被分配到六个组:对照组和五个感染后组(第 1、3、5、7 和 9 天)。经过 15 天的微生物群稳定期后,感染鸡通过眼部、鼻内和气管内途径接受病毒接种体(107 TCID50/ml)。对气管和支气管肺泡灌洗液样本进行了分析。与 d0 对照组相比,在感染后第 5、7 和 9 天观察到微生物群多样性显著减少。永久多变量方差分析证实,感染组和未感染组之间存在显著的贝塔多样性差异(P = 0.001)。从第 5 天到第 9 天,微生物的变化主要表现为变形菌增加、放线菌和固缩菌减少,以及菊形菌增加。d5时Ⅰ型干扰素(IFN-β)和蝰蛇素基因表达的升高与微生物群多样性的降低相吻合,突出了呼吸道微生物群在调节宿主对AIV H9N2感染的反应中的作用,并提出了呼吸道菌群失调的潜在生物标记物。
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引用次数: 0
Silica hydrogels as a carbon-free solid media for the culture of diverse organisms. 二氧化硅水凝胶作为一种无碳固体培养基,用于多种生物的培养。
Pub Date : 2024-12-28 eCollection Date: 2025-01-01 DOI: 10.1093/femsmc/xtae035
Druhi Vaid, Alisa Zubir, Alistair Hanak, Tanda Qi, Daniela Delneri, Lu Shin Wong

Bacteriological agar plates are commonly used to carry out experiments for the selective growth of microorganisms and the isolation of single-strain colonies. However, the presence of agar itself may be a confounding factor since it may serve as a source of carbon and energy. Moreover, there have been ongoing constraints on the production and sourcing of agar. These concerns have led to an interest in the development of agar substitutes. Silica hydrogels are entirely inorganic carbon-free polymeric materials that lack any source of micronutrients. Herein, a revised method for the preparation of silica hydrogels as a solid culture medium is reported. These gels can be formulated with a range of nutrient-rich or minimal media supplemented with various carbon sources, and can be manipulated in the same manner as agar gels. Their use for the culture and isolation of diverse microorganisms, including both Gram-positive and Gram-negative bacteria, yeast, and filamentous fungi is demonstrated. These silica hydrogels supplemented with either antibiotics or other molecules of interest can also be used for microbial selection experiments.

细菌学琼脂平板通常用于进行微生物选择性生长和单株菌落分离的实验。然而,琼脂本身的存在可能是一个混淆因素,因为它可以作为碳和能量的来源。此外,琼脂的生产和采购一直受到限制。这些问题引起了人们对琼脂替代品发展的兴趣。二氧化硅水凝胶是完全无机的无碳聚合物材料,缺乏任何微量营养素来源。本文报道了一种用于制备二氧化硅水凝胶作为固体培养基的改进方法。这些凝胶可以用一系列富含营养或添加各种碳源的最小培养基配制,并且可以像琼脂凝胶一样以相同的方式进行操作。它们用于培养和分离各种微生物,包括革兰氏阳性和革兰氏阴性细菌、酵母和丝状真菌。这些二氧化硅水凝胶补充抗生素或其他感兴趣的分子也可用于微生物选择实验。
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引用次数: 0
Proteomic identification of a Toxoplasma gondii sporozoite-specific antigen using HDAC3 inhibitor-treated tachyzoites as surrogate. 以 HDAC3 抑制剂处理过的幼虫为替代物,从蛋白质组学角度鉴定弓形虫孢子虫特异性抗原。
Pub Date : 2024-12-23 eCollection Date: 2025-01-01 DOI: 10.1093/femsmc/xtae034
David Warschkau, Sandra Klein, Ella Schadt, Joerg Doellinger, Gereon Schares, Frank Seeber

The apicomplexan parasite Toxoplasma gondii has a complex life cycle. Access to sexual stages and sporozoite-containing oocysts, essential for studying the parasite's environmental transmission, is limited and requires animal experiments with cats. Thus, alternatives and resource-efficient methods are needed. Several molecular factors and transcriptional switches responsible for differentiation have been identified in recent years. In tachyzoites, drug-induced inhibition of the histone deacetylase HDAC3, or genetic depletion of transcription factors regulating HDAC3, leads to the expression of genes that are specific to sexual stages and oocysts. Here, we applied this concept and showed that the commercially available HDAC3 inhibitor apicidin could be used to identify the hitherto unknown antigen of the sporozoite-specific monoclonal antibody G1/19 in tachyzoites. Using mass spectrometry of immunoprecipitated G1/19 target protein from apicidin-treated cultures, we identified it as SporoSAG. In addition, for the much less abundant sporozoite-specific protein LEA860, apicidin treatment was still sufficient to induce a detectable protein level in immunofluorescence microscopy. We also discuss further applications and the limitations of this approach. This allows to overcome issues with the paucity of material of sexual stages and oocysts from T. gondii to some extent without the need for cat-derived material.

刚地弓形虫是一种顶复体寄生虫,具有复杂的生命周期。进入有性阶段和含有孢子子的卵囊对研究寄生虫的环境传播至关重要,但接触这些卵囊的机会有限,而且需要在猫身上进行动物实验。因此,需要替代方法和资源效率高的方法。近年来,一些分子因子和转录开关负责分化已被确定。在速虫中,药物诱导的组蛋白去乙酰化酶HDAC3的抑制,或调节HDAC3的转录因子的基因缺失,会导致性阶段和卵囊特异性基因的表达。在这里,我们应用了这一概念,并证明了市上可用的HDAC3抑制剂apicidin可用于鉴定速殖子中孢子体特异性单克隆抗体G1/19的迄今未知抗原。通过对apicidin处理培养物免疫沉淀G1/19靶蛋白的质谱分析,我们鉴定其为SporoSAG。此外,对于少得多的孢子体特异性蛋白LEA860, apicidin处理仍然足以在免疫荧光显微镜下诱导可检测到的蛋白水平。我们还讨论了这种方法的进一步应用和局限性。这可以在一定程度上克服弓形虫性阶段和卵囊材料缺乏的问题,而不需要猫源材料。
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引用次数: 0
Evaluating the impact of redox potential on the growth capacity of anaerobic gut fungi. 评估氧化还原电位对厌氧肠道真菌生长能力的影响。
Pub Date : 2024-11-05 eCollection Date: 2024-01-01 DOI: 10.1093/femsmc/xtae033
Emma E England, Carrie J Pratt, Mostafa S Elshahed, Noha H Youssef

Anaerobic gut fungi (AGF, Neocallimastigomycota) inhabit the alimentary tract of herbivores. Although strict anaerobes, studies have suggested their capacity to retain viability after various durations of air exposure. It is currently unclear whether AGF can actively grow, and not merely survive, in redox potentials (Eh) higher than those encountered in the herbivorous gut. We evaluated the growth of two AGF strains (Orpinomyces joyonii and Testudinimyces gracilis) at various Eh levels, achieved by manipulating the concentrations of reductant (cysteine hydrochloride) in culture media. Both strains exhibited robust and sustainable growth at negative Eh (-50 mV or below). However, growth in the absence of cysteine hydrochloride (Eh value around +50 mV) was possible only for O. joyonii and only for one subcultivation. The capacity to grow at +50 mV was further confirmed in four additional taxa (Pecoramyces ruminatium, Anaeromyces mucronatus, Aklioshbmyces papillarum, and Piromyces communis), while two (Aestipascuomyces dupliciliberans and Capellomyces foraminis) failed to grow under these conditions. Our results establish the ability of AGF to grow at redox potential values higher than those encountered in their natural habitats. Such capability could contribute to efficient AGF dispersal and horizontal transmission between hosts, and could have important implications for industrial applications of AGF.

厌氧肠道真菌(AGF,Neocallimastigomycota)栖息在食草动物的消化道中。虽然是严格的厌氧菌,但研究表明它们在暴露于不同时间的空气后仍能保持活力。目前还不清楚 AGF 在氧化还原电位(Eh)高于食草动物肠道中的氧化还原电位时是否能积极生长,而不仅仅是存活。我们通过调节培养基中还原剂(半胱氨酸盐酸盐)的浓度,评估了两种 AGF 菌株(Orpinomyces joyonii 和 Testudinimyces gracilis)在不同 Eh 水平下的生长情况。这两种菌株在负 Eh(-50 mV 或更低)条件下均表现出强劲和可持续的生长。然而,只有 O. joyonii 能在没有盐酸半胱氨酸的情况下(Eh 值约为 +50 mV)生长,而且只进行了一次亚培养。另外四个类群(Pecoramyces ruminatium、Anaeromyces mucronatus、Aklioshbmyces papillarum 和 Piromyces communis)在 +50 mV 下的生长能力也得到了进一步证实,而两个类群(Aestipascuomyces dupliciliberans 和 Capellomyces foraminis)则未能在这些条件下生长。我们的研究结果证明,AGF 有能力在高于其自然栖息地氧化还原电位值的条件下生长。这种能力可能有助于 AGF 在宿主间的高效传播和水平传播,并对 AGF 的工业应用具有重要意义。
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引用次数: 0
Contact with young children is a major risk factor for pneumococcal colonization in older adults. 与幼儿接触是老年人肺炎球菌定植的主要风险因素。
Pub Date : 2024-10-14 eCollection Date: 2024-01-01 DOI: 10.1093/femsmc/xtae032
Anne L Wyllie, Devyn Yolda-Carr, Maikel S Hislop, Sidiya Mbodj, Loren Wurst, Pari Waghela, Ronika Alexander-Parrish, Lindsay R Grant, Adriano Arguedas, Bradford D Gessner, Daniel M Weinberger

Important questions remain about the sources of transmission of pneumococcus to older adults in the community. This is critical for understanding the potential effects of using pneumococcal conjugate vaccines (PCVs) in children and older adults. For non-institutionalized individuals, we hypothesized that the most likely source of adult-to-adult transmission is within the household. We designed a longitudinal study to sample adults ≥60 years of age living in the same household (New Haven, CT, USA), without younger residents in the household. Saliva samples and social and health questionnaires were obtained every 2 weeks for a period of 10 weeks. DNA extracted from culture-enriched saliva was tested using qPCR for pneumococcus genes piaB, lytA, and serotype. Across two study seasons (November 2020-August 2021, November 2021-September 2022), 121 individuals from 61 households completed all six visits; 62 individuals were enrolled in both seasons. Overall, 52/1088 (4.8%) samples tested positive for pneumococcus, with 27/121 (22.3%) individuals colonized at least once. Several individuals were colonized at multiple time points; two individuals were colonized at 5/6 time points and two at all six. In 5 instances, both household members were carriers in the same season, though not necessarily at the same time. Pneumococcal carriage was substantially higher among individuals who had contact with children (10.0% vs. 1.6%). Contact with young children was the most important factor that influenced pneumococcal acquisition rates. While there were several instances where both adult household members were colonized at the same time or at sequential visits, these individuals typically had contact with children. As such, PCV immunization can directly protect older adults who have contact with children.

关于肺炎球菌在社区中传播给老年人的来源,仍然存在一些重要的问题。这对于了解在儿童和老年人中使用肺炎球菌结合疫苗 (PCV) 的潜在效果至关重要。对于非住院个人,我们假设最有可能的成人间传播源是家庭内部。我们设计了一项纵向研究,对生活在同一家庭(美国康涅狄格州纽黑文)中年龄≥60 岁的成年人进行抽样调查,该家庭中没有年轻居民。在为期 10 周的时间里,每两周采集一次唾液样本并进行社会和健康问卷调查。从培养富集的唾液中提取的 DNA 采用 qPCR 方法检测肺炎球菌基因 piaB、lytA 和血清型。在两个研究季节(2020 年 11 月至 2021 年 8 月,2021 年 11 月至 2022 年 9 月)中,来自 61 个家庭的 121 人完成了全部六次访问;两个季节中均有 62 人注册。总体而言,52/1088(4.8%)份样本的肺炎球菌检测结果呈阳性,其中 27/121(22.3%)人至少定植过一次。有几个人在多个时间点都有定植;两个人在 5/6 个时间点都有定植,两个人在全部 6 个时间点都有定植。在 5 个案例中,两个家庭成员在同一季节都是携带者,但不一定在同一时间。在与儿童接触的人群中,肺炎球菌携带率要高得多(10.0% 对 1.6%)。与幼儿接触是影响肺炎球菌感染率的最重要因素。虽然有几例成年家庭成员同时或相继感染的情况,但这些人通常都与儿童有接触。因此,接种 PCV 可以直接保护与儿童有接触的老年人。
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引用次数: 0
Trivalent immunization with metal-binding proteins confers protection against enterococci in a mouse infection model. 在小鼠感染模型中,金属结合蛋白的三价免疫可提供对肠球菌的保护。
Pub Date : 2024-10-03 eCollection Date: 2024-01-01 DOI: 10.1093/femsmc/xtae031
Ling Ning Lam, Angie Sedra, Jessica Kajfasz, Aym Berges, Irene S Saengpet, Grace Adams, Jeffery Fairman, José A Lemos

Enterococcus faecalis is ranked among the top five bacterial pathogens responsible for catheter-associated urinary tract infections, wound infections, secondary root canal infections, and infective endocarditis. Previously, we showed that inactivation of either the manganese- and iron-binding (EfaA) or zinc-binding (AdcA and AdcAII) lipoproteins significantly reduced E. faecalis virulence. Here, we explored whether immunization using a multi-valent approach induces protective immunity against systemic enterococcal infections. We found that multi-antigen antisera raised against EfaA, AdcA, and AdcAII displayed similar capacities to initiate neutrophil-mediated opsonization, like their single-antigen counterparts. Further, these antigen-specific antibodies worked synergistically with calprotectin, a divalent host metal chelator, to inhibit the growth of E. faecalis in laboratory media as well as in human sera. Using the Galleria mellonella invertebrate model and mouse peritonitis model, we showed that passive immunization with multi-antigen antisera conferred robust protection against E. faecalis infection, while the protective effects of single antigen antisera were negligible in G. mellonella, and negligible-to-moderate in the mouse model. Lastly, active immunization with the 3-antigen (trivalent) cocktail significantly protected mice against either lethal or non-lethal E. faecalis infections, with this protection appearing to be far-reaching based on immunization results obtained with contemporary strains of E. faecalis and closely related Enterococcus faecium.

粪肠球菌是导致导管相关性尿路感染、伤口感染、继发性根管感染和感染性心内膜炎的五大细菌病原体之一。此前,我们曾发现,灭活锰和铁结合脂蛋白(EfaA)或锌结合脂蛋白(AdcA 和 AdcAII)可显著降低粪肠球菌的毒力。在此,我们探讨了使用多价方法进行免疫是否能诱导针对全身性肠球菌感染的保护性免疫。我们发现,针对 EfaA、AdcA 和 AdcAII 的多抗原抗血清与单抗原抗血清具有相似的启动中性粒细胞介导的吸附能力。此外,这些抗原特异性抗体与二价宿主金属螯合剂 calprotectin 协同作用,抑制粪肠球菌在实验室培养基和人类血清中的生长。我们利用无脊椎鼠模型和小鼠腹膜炎模型研究发现,多抗原抗血清被动免疫能有效防止粪肠球菌感染,而单一抗原抗血清对无脊椎鼠的保护作用微乎其微,对小鼠模型的保护作用也微乎其微。最后,使用三抗原(三价)鸡尾酒进行主动免疫可显著保护小鼠免受致死性或非致死性粪肠球菌感染,根据对当代粪肠球菌菌株和密切相关的粪肠球菌进行免疫的结果,这种保护似乎影响深远。
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FEMS microbes
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