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Genetic and molecular characterization of fit95 mutation of Escherichia coli: evidence that fit95 is an allele of pheT 大肠杆菌 fit95 突变的遗传和分子特征:fit95 是 pheT 等位基因的证据。
IF 2.3 3区 生物学 Q3 MICROBIOLOGY Pub Date : 2024-09-24 DOI: 10.1007/s00203-024-04127-9
Praveen Belagal

The originally identified transcription-defective fitA76 temperature-sensitive (Ts) mutation defined an allele of pheS. Both fitA/pheS and fitB/pheT were previously proposed to function as transcription factors. Sequencing pheS region of the fitA76 mutant revealed the same G293→A293 transition found in the translation-defective pheS5 mutant. It was subsequently found that fitA76 harbored a second mutation (fit95) in addition to pheS5 mutation. The fit95 was found to be Ts on –salt media but was found unstable. In this investigation, genetic, physiological and molecular characterization of the fit95 mutation was carried out. The fit95 was genetically re-separated from the pheS5 mutation present in the fitA76 mutant and the same was subsequently mobilized into multiple genetic backgrounds to study its phenotypic modulations by altering the medium and supplements. Based on genetic studies, the unstable –salt Ts phenotype of the fit95 could be stabilized by the presence of rpoB201 mutation. Addition of glucose enhanced Ts phenotype in the presence of rpoB201 mutation, but citrate completely alleviated the Ts phenotype. Further, by series of complementation analyses and molecular cloning, the identity of fit95 was revealed as pheT gene which is part of pheST operon.

最初发现的转录缺陷 fitA76 温度敏感(Ts)突变定义了 pheS 的一个等位基因。此前,fitA/pheS 和 fitB/pheT 都被认为具有转录因子的功能。对 fitA76 突变体的 pheS 区域进行测序,发现与翻译缺陷的 pheS5 突变体相同的 G293→A293 转换。随后发现,除了pheS5突变外,fitA76还存在第二个突变(fit95)。发现 fit95 在盐培养基上是 Ts,但不稳定。本研究对 fit95 突变体进行了遗传学、生理学和分子鉴定。将 fit95 从 fitA76 突变体中的 pheS5 突变基因中重新分离出来,然后将其移入多种遗传背景中,通过改变培养基和补充剂来研究其表型变化。根据遗传学研究,fit95 的不稳定盐 Ts 表型可以通过 rpoB201 突变的存在而得到稳定。在 rpoB201 突变的情况下,添加葡萄糖会增强 Ts 表型,但柠檬酸盐会完全缓解 Ts 表型。此外,通过一系列的互补分析和分子克隆,还揭示了 fit95 的身份是 pheT 基因,它是 pheST 操作子的一部分。
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引用次数: 0
Paracraurococcus lichenis sp. nov., isolated from lichen in Thailand Paracraurococcus lichenis sp.
IF 2.3 3区 生物学 Q3 MICROBIOLOGY Pub Date : 2024-09-24 DOI: 10.1007/s00203-024-04129-7
Engkarat Kingkaew, Shingo Kato, Takao Iino, Takashi Itoh, Moriya Ohkuma, Wongsakorn Phongsopitanun, Somboon Tanasupawat

A novel bacterium, designated as strain LOR1-02T and isolated from a lichen sample collected from Kham Riang Subdistrict, Kantharawichai District, Maha Sarakham Province, Thailand, underwent thorough investigation utilizing a polyphasic taxonomic approach. Strain LOR1-02T demonstrated growth within a temperature range of 20–42 °C (optimal at 30 °C), pH range of 5.0–7.5 (optimal at pH 7.0), and tolerance to 4.0% (w/v) NaCl. Phylogenetic analysis revealed its close relation to Paracraurococcus ruber JCM 9931T, with a 16S rRNA gene sequence similarity of 97.16%, placing it within the genus Paracraurococcus. The approximate genome size of strain LOR1-02T was determined to be 8.6 Mb, with a G + C content of 70.9 mol%. Additionally, ANIb, ANIm, and AAI values between the whole genomes of strain LOR1-02T and type strains were calculated as 82.6–83.4%, 86.1–86.8%, and 81.4–82.2%, respectively, while the dDDH value was determined to be 26.3–28.5% (C.I. 24.0–31.0%). The predominant fatty acids detected were C18:1ω7c and/or C18:1ω6c, C16:0, and C18:12OH. The major ubiquinone identified was Q-10, and the polar lipids included phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, diphosphatidylglycerol, along with unidentified phosphoaminolipid, lipids, and an amino lipid. Based on comprehensive phenotypic, chemotaxonomic, and genotypic characterization, it is concluded that strain LOR1-02T represents a novel species within the genus Paracraurococcus, for which the name Paracraurococcus lichenis sp. nov. is proposed. The type strain designation is LOR1-02T (= JCM 33121T = NBRC 112776T = TISTR 2503T).

我们采用多相分类法对从泰国玛哈沙拉堪府甘塔拉威猜县甘凉分区采集的地衣样本中分离出的一种新型细菌进行了深入研究,并将其命名为菌株 LOR1-02T。菌株 LOR1-02T 的生长温度范围为 20-42°C(最适温度为 30°C),pH 值范围为 5.0-7.5(最适 pH 值为 7.0),耐受 4.0% (w/v) NaCl。系统进化分析表明,该菌株与 Paracraurococcus ruber JCM 9931T 关系密切,16S rRNA 基因序列相似度为 97.16%,属于 Paracraurococcus 属。菌株 LOR1-02T 的基因组大小约为 8.6 Mb,G+C 含量为 70.9 mol%。此外,计算得出菌株 LOR1-02T 和类型菌株全基因组的 ANIb、ANIm 和 AAI 值分别为 82.6-83.4%、86.1-86.8% 和 81.4-82.2%,dDDH 值为 26.3-28.5%(C.I. 24.0-31.0%)。检测到的主要脂肪酸为 C18:1ω7c 和/或 C18:1ω6c、C16:0 和 C18:12OH。鉴定出的主要泛醌是 Q-10,极性脂质包括磷脂酰甘油、磷脂酰乙醇胺、磷脂酰胆碱、二磷脂酰甘油以及不明的磷胺脂、脂质和一种氨基脂质。根据全面的表型、化学分类学和基因型鉴定,认为菌株 LOR1-02T 代表 Paracraurococcus 属中的一个新物种,并将其命名为 Paracraurococcus lichenis sp.模式菌株命名为 LOR1-02T(= JCM 33121T = NBRC 112776T = TISTR 2503T)。
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引用次数: 0
Antimicrobial peptide-based strategies to overcome antimicrobial resistance 基于抗菌肽的克服抗菌药耐药性战略。
IF 2.3 3区 生物学 Q3 MICROBIOLOGY Pub Date : 2024-09-23 DOI: 10.1007/s00203-024-04133-x
Meetali Girdhar, Aparajita Sen, Arti Nigam, Jyoti Oswalia, Sachin Kumar, Rashi Gupta

Antibiotic resistance has emerged as a global threat, rendering the existing conventional treatment strategies ineffective. In view of this, antimicrobial peptides (AMPs) have proven to be potent alternative therapeutic interventions with a wide range of applications in clinical health. AMPs are small peptides produced naturally as a part of the innate immune responses against a broad range of bacterial, fungal and viral pathogens. AMPs present a myriad of advantages over traditional antibiotics, including their ability to target multiple sites, reduced susceptibility to resistance development, and high efficacy at low doses. These peptides have demonstrated notable potential in inhibiting microbes resistant to traditional antibiotics, including the notorious ESKAPE pathogens, recognized as the primary culprits behind nosocomial infections. AMPs, with their multifaceted benefits, emerge as promising candidates in the ongoing efforts to combat the escalating challenges posed by antibiotic resistance. This in-depth review provides a detailed discussion on AMPs, encompassing their classification, mechanism of action, and diverse clinical applications. Focus has been laid on combating newly emerging drug-resistant organisms, emphasizing the significance of AMPs in mitigating this pressing challenge. The review also illuminates potential future strategies that may be implemented to improve AMP efficacy, such as structural modifications and using AMPs in combination with antibiotics and matrix-inhibiting compounds.

Graphical abstract

抗生素耐药性已成为一种全球性威胁,使现有的常规治疗策略无法奏效。有鉴于此,抗菌肽(AMPs)已被证明是一种有效的替代治疗干预措施,在临床健康领域有着广泛的应用。AMPs 是一种天然产生的小肽,是先天性免疫反应的一部分,可对抗多种细菌、真菌和病毒病原体。与传统抗生素相比,AMPs 具有许多优势,包括能够靶向多个部位、降低抗药性产生的敏感性以及低剂量高效等。这些肽在抑制对传统抗生素产生抗药性的微生物方面具有显著的潜力,其中包括臭名昭著的 ESKAPE 病原体,它们被公认为造成医院内感染的罪魁祸首。AMPs 有着多方面的优势,在应对抗生素耐药性不断升级的挑战中成为前景广阔的候选药物。这篇深度综述详细讨论了 AMPs,包括其分类、作用机制和各种临床应用。重点放在对抗新出现的耐药生物上,强调了 AMPs 在缓解这一紧迫挑战方面的重要作用。综述还阐明了未来可能实施的提高 AMP 药效的策略,如结构改造以及将 AMP 与抗生素和基质抑制化合物结合使用。
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引用次数: 0
Population distribution characteristics of mating type genes and genetic stability in Morchella sextelata 交配型基因的种群分布特征和六角森氏杆菌的遗传稳定性。
IF 2.3 3区 生物学 Q3 MICROBIOLOGY Pub Date : 2024-09-23 DOI: 10.1007/s00203-024-04141-x
Chunfeng Mu, Chen Hao, Lunhe You, Yichun Wang, Sheng Qiang, Yu Liu, Jianrui Wang

The reproductive mode of morels (Morchella spp.) is governed by mating type genes, specifically MAT1-1 and MAT1-2. This study investigated the presence of mating type genes at various growth stages and in different parts of cultivated Morchella sextelata. This study revealed significant fluctuations in the detection ratio of the two mating type genes during ascocarps growth. Single ascospore strains with MAT1-1, MAT1-2 and both mating types were selected for experimentations. Stress stimuli including H2O2, Congo red and NaCl were introduced into the medium. Differences in the cultural and physiological characteristics of single spore strains were analyzed, and mating type genes were identified after subculturing to assess their stability. The results indicated that a total of 297 samples with a single mating type gene were detected in 480 samples selected from the five stages of fruiting body growth, accounting for 61.9%. Stress exposure influenced colony morphology, mycelial growth rate, and biomass, leading to significant increases in malondialdehyde content and osmotic adjustment compounds, including soluble protein and proline. Physiological and biochemical parameters varied among the three mating type strains under different stress conditions. Principal component analysis was used to calculate the weight values, which showed that the MAT1-2 strain exhibited the highest tolerance to chemical stresses, particularly oxidative stress. Subculturing under stress revealed that single mating type strains ceased growth by the 8th generation, whereas both mating type strains could continue to the 15th generation without loss of mating type genes, indicating broader environmental adaptability and higher viability. These findings offer novel insights into mating type gene function and serve as a scientific foundation for the development of high-yield, stress-resistant morel varieties.

羊肚菌(Morchella spp.)的繁殖模式受交配型基因(特别是 MAT1-1 和 MAT1-2)控制。本研究调查了交配型基因在栽培羊肚菌不同生长阶段和不同部位的存在情况。研究发现,在腹孢子虫的生长过程中,这两种交配型基因的检测比例有明显的波动。实验选择了具有 MAT1-1、MAT1-2 和两种交配类型的单个 ascospore 菌株。在培养基中引入 H2O2、刚果红和氯化钠等应激刺激。分析了单孢子菌株培养和生理特性的差异,并在亚培养后鉴定了交配型基因,以评估其稳定性。结果表明,从子实体生长的五个阶段选取的 480 个样本中,共检测到 297 个具有单一交配型基因的样本,占 61.9%。压力暴露影响了菌落形态、菌丝生长速度和生物量,导致丙二醛含量和渗透调节化合物(包括可溶性蛋白质和脯氨酸)显著增加。在不同胁迫条件下,三种交配型菌株的生理生化参数各不相同。采用主成分分析法计算重量值,结果表明 MAT1-2 株系对化学胁迫,尤其是氧化胁迫的耐受性最高。在胁迫条件下进行亚培养发现,单一交配型菌株在第8代时停止生长,而两种交配型菌株都能延续到第15代,且交配型基因没有丢失,这表明交配型菌株具有更广泛的环境适应性和更高的存活率。这些发现为了解交配型基因的功能提供了新的视角,为开发高产、抗逆的羊肚菌品种奠定了科学基础。
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引用次数: 0
Phenotypic and genotypic perspectives on detection methods for bacterial antimicrobial resistance in a One Health context: research progress and prospects 从表型和基因型角度看 "一体健康 "背景下细菌抗菌药耐药性的检测方法:研究进展与前景。
IF 2.3 3区 生物学 Q3 MICROBIOLOGY Pub Date : 2024-09-20 DOI: 10.1007/s00203-024-04131-z
Bingbing Yang, Xiaoqi Xin, Xiaoqing Cao, Lubanga Nasifu, Zhenlin Nie, Bangshun He

The widespread spread of bacterial antimicrobial resistance (AMR) and multidrug-resistant bacteria poses a significant threat to global public health. Traditional methods for detecting bacterial AMR are simple, reproducible, and intuitive, requiring long time incubation and high labor intensity. To quickly identify and detect bacterial AMR is urgent for clinical treatment to reduce mortality rate, and many new methods and technologies were required to be developed. This review summarizes the current phenotypic and genotypic detection methods for bacterial AMR. Phenotypic detection methods mainly include antimicrobial susceptibility tests, while genotypic detection methods have higher sensitivity and specificity and can detect known or even unknown drug resistance genes. However, most of the current tests are either genotypic or phenotypic and rarely combined. Combining the advantages of phenotypic and genotypic methods, combined with the joint application of multiple rapid detection methods may be the trend for future AMR testing. Driven by rapid diagnostic technology, big data analysis, and artificial intelligence, detection methods of bacterial AMR are expected to constantly develop and innovate. Adopting rational detection methods and scientific data analysis can better address the challenges of bacterial AMR and ensure human health and social well-being.

细菌抗药性(AMR)和耐多药细菌的广泛传播对全球公共卫生构成了重大威胁。传统的细菌 AMR 检测方法简单、可重复、直观,需要长时间培养,劳动强度大。快速识别和检测细菌 AMR 对临床治疗降低死亡率迫在眉睫,因此需要开发许多新方法和新技术。本综述总结了目前细菌 AMR 的表型和基因型检测方法。表型检测方法主要包括抗菌药物药敏试验,而基因型检测方法具有更高的灵敏度和特异性,可检测已知甚至未知的耐药基因。然而,目前大多数检测方法要么是基因型检测,要么是表型检测,很少将两者结合起来。结合表型和基因型方法的优势,联合应用多种快速检测方法可能是未来 AMR 检测的趋势。在快速诊断技术、大数据分析和人工智能的推动下,细菌 AMR 的检测方法有望不断发展和创新。采用合理的检测方法和科学的数据分析可以更好地应对细菌 AMR 的挑战,保障人类健康和社会福祉。
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引用次数: 0
Effect of Staphylococcus aureus colonization and immune defects on the pathogenesis of atopic dermatitis 金黄色葡萄球菌定植和免疫缺陷对特应性皮炎发病机制的影响。
IF 2.3 3区 生物学 Q3 MICROBIOLOGY Pub Date : 2024-09-20 DOI: 10.1007/s00203-024-04134-w
Evrim Özdemіr, Lütfiye Öksüz

Atopic dermatitis (AD) is a common and recurrent skin disease characterized by skin barrier dysfunction, inflammation and chronic pruritus, with wide heterogeneity in terms of age of onset, clinical course and persistence over the lifespan. Although the pathogenesis of the disease are unclear, epidermal barrier dysfunction, immune and microbial dysregulation, and environmental factors are known to be critical etiologies in AD pathology. The skin microbiota represents an ecosystem consisting of numerous microbial species that interact with each other as well as host epithelial cells and immune cells. Although the skin microbiota benefits the host by supporting the basic functions of the skin and preventing the colonization of pathogens, disruption of the microbial balance (dysbiosis) can cause skin diseases such as AD. Although AD is a dermatological disease, recent evidence has shown that changes in microbiota composition in the skin and intestine contribute to the pathogenesis of AD. Environmental factors that contribute to skin barrier dysfunction and microbial dysbiosis in AD include allergens, diet, irritants, air pollution, epigenetics and microbial exposure. Knowing the microbial combination of intestin, as well as the genetic and epigenetic determinants associated with the development of autoantibodies, may help elucidate the pathophysiology of the disease. The skin of patients with AD is characterized by microbial dysbiosis as a result of reduced microbial diversity and overgrowth of the pathogens such as Staphylococcus aureus. Recent studies have revealed the importance of building a strong immune response against microorganisms during childhood and new mechanisms of microbial community dynamics in modulating the skin microbiome. Numerous microorganisms are reported to modulate host response through communication with keratinocytes, specific immune cells and adipocytes to improve skin health and barrier function. This growing insight into bioactive substances in the skin microbiota has led to novel biotherapeutic approaches targeting the skin surface for the treatment of AD. This review will provide an updated overview of the skin microbiota in AD and its complex interaction with immune response mechanisms, as well as explore possible underlying mechanisms in the pathogenesis of AD and provide insights into new therapeutic developments for the treatment of AD. It also focuses on restoring skin microbial homeostasis, aiming to reduce inflammation by repairing the skin barrier.

特应性皮炎(AD)是一种常见的复发性皮肤病,以皮肤屏障功能障碍、炎症和慢性瘙痒为特征,在发病年龄、临床过程和持续寿命方面具有广泛的异质性。虽然该病的发病机制尚不清楚,但已知表皮屏障功能障碍、免疫和微生物失调以及环境因素是 AD 病理学的关键病因。皮肤微生物群是一个生态系统,由众多微生物物种组成,它们与宿主上皮细胞和免疫细胞相互作用。虽然皮肤微生物群通过支持皮肤的基本功能和防止病原体的定植对宿主有益,但微生物平衡的破坏(菌群失调)可导致 AD 等皮肤疾病。虽然 AD 是一种皮肤病,但最近的证据表明,皮肤和肠道中微生物群组成的变化也是 AD 的发病机制之一。导致 AD 皮肤屏障功能障碍和微生物菌群失调的环境因素包括过敏原、饮食、刺激物、空气污染、表观遗传学和微生物暴露。了解肠道微生物的组合以及与自身抗体发生相关的遗传和表观遗传决定因素,可能有助于阐明该病的病理生理学。由于微生物多样性减少和金黄色葡萄球菌等病原体过度生长,AD 患者皮肤的特点是微生物菌群失调。最近的研究揭示了在儿童时期建立针对微生物的强大免疫反应的重要性,以及微生物群落动态调节皮肤微生物组的新机制。据报道,许多微生物通过与角质细胞、特异性免疫细胞和脂肪细胞的交流来调节宿主反应,从而改善皮肤健康和屏障功能。人们对皮肤微生物群中生物活性物质的了解日益加深,从而产生了针对皮肤表面的新型生物治疗方法,用于治疗急性皮肤炎。本综述将提供有关 AD 中皮肤微生物群及其与免疫反应机制之间复杂相互作用的最新概述,探讨 AD 发病机制的可能潜在机制,并为治疗 AD 的新疗法开发提供见解。它还关注恢复皮肤微生物的平衡,旨在通过修复皮肤屏障来减轻炎症。
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引用次数: 0
Integrated subtractive genomics and structure-based approach to unravel the therapeutic drug target of Leishmania species 综合减法基因组学和基于结构的方法,揭示利什曼原虫的治疗药物靶点。
IF 2.3 3区 生物学 Q3 MICROBIOLOGY Pub Date : 2024-09-19 DOI: 10.1007/s00203-024-04118-w
Debanjan Saha, Anupam Nath Jha

Leishmaniasis is a complex vector-borne disease caused by intracellular protozoan parasites of the Leishmania genus. It presents a significant public health challenge in tropical and subtropical regions globally. As resistance to treatment increases, managing and controlling Leishmaniasis becomes more challenging, necessitating innovative approaches. To address this challenge, our study utilized subtractive genomics and structure-based approaches to identify common drug targets and combat antimicrobial resistance (AMR) across five Leishmania species strains. The subtractive genomics approach unraveled Glutamate Dehydrogenase (GDH) as a promising drug target for treating Leishmania infections. The investigation considered established methodologies observed in analogous studies, orthologous group, and druggability tests. Multiple sequence alignment revealed conserved sequences in GDH, while phylogenetic tree analysis provided insights into the evolutionary origin and close relationships of GDH across Leishmania species. Conserved sequences in GDH along with its function in pathogenicity provided insights into the close relationships of GDH across Leishmania species. Using a structure-based approach, our study showed the molecular interactions between GDH and three ligands—Bithionol, GW5074, and Hexachlorophene—through molecular docking and 100 ns molecular dynamics (MD) simulations. GW5074 exhibited a significant affinity for GDH, as indicated by stable RMSD values, a more compact conformation, and a higher number of hydrogen bonds than Bithionol. MMPBSA analysis confirmed the superior binding energy of the GW5074-GDH complex, emphasizing its potential as a potent ligand for drug development. This comprehensive analysis identified GW5074 as a promising candidate for inhibiting GDH activities in Leishmania species, contributing to the development of effective therapeutics against Leishmania infections.

利什曼病是由利什曼属细胞内原生动物寄生虫引起的一种复杂的病媒传播疾病。它对全球热带和亚热带地区的公共卫生构成重大挑战。随着抗药性的增加,利什曼病的管理和控制变得更具挑战性,需要采取创新方法。为了应对这一挑战,我们的研究采用了减法基因组学和基于结构的方法来确定共同的药物靶点,并在五个利什曼病种菌株中对抗抗菌药耐药性(AMR)。减法基因组学方法揭示了谷氨酸脱氢酶(GDH)是治疗利什曼病感染的一个有希望的药物靶点。这项研究考虑了在类比研究、同源组和可药性测试中观察到的既定方法。多重序列比对揭示了 GDH 中的保守序列,而系统发生树分析则为了解 GDH 在不同利什曼原虫物种中的进化起源和密切关系提供了见解。GDH 中的保守序列及其致病功能有助于深入了解 GDH 在不同利什曼原虫中的密切关系。我们的研究采用基于结构的方法,通过分子对接和 100 ns 分子动力学(MD)模拟,展示了 GDH 与三种配体--硫醇、GW5074 和六氯芬--之间的分子相互作用。与 Bithionol 相比,GW5074 表现出稳定的 RMSD 值、更紧凑的构象和更多的氢键,因此对 GDH 有明显的亲和力。MMPBSA 分析证实了 GW5074-GDH 复合物的超强结合能,强调了其作为药物开发的强效配体的潜力。这项综合分析确定了 GW5074 是抑制利什曼原虫 GDH 活性的有希望的候选药物,有助于开发针对利什曼原虫感染的有效疗法。
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引用次数: 0
Effects of AI-2 quorum sensing related luxS gene on Streptococcus suis formatting monosaccharide metabolism-dependent biofilm 与 AI-2 法定量感应相关的 luxS 基因对猪链球菌格式化单糖代谢依赖性生物膜的影响
IF 2.3 3区 生物学 Q3 MICROBIOLOGY Pub Date : 2024-09-19 DOI: 10.1007/s00203-024-04126-w
Shuji Gao, Shuo Yuan, Yingying Quan, Wenjie Jin, Yamin Shen, Baobao Liu, Yuxin Wang, Yang Wang

Biofilm is the primary cause of persistent infections caused by Streptococcus suis (S. suis). Metabolism and AI-2 quorum sensing are intricately linked to S. suis biofilm formation. Although the role of the AI-2 quorum sensing luxS gene in S. suis biofilm has been reported, its specific regulatory mechanism remains unclear. This study explored the differences in biofilm formation and monosaccharide metabolism among the wild type (WT), luxS mutant (ΔluxS) and complement strain (CΔluxS), and Galleria mellonella larvae were used to access the effect of luxS gene deletion on the virulence of S. suis in different monosaccharide medias. The results indicated that deletion of the luxS gene further compromised the monosaccharide metabolism of S. suis, impacting its growth in media with fructose, galactose, rhamnose, and mannose as the sole carbon sources. However, no significant impact was observed in media with glucose and N-acetylglucosamine. This deletion also weakened EPS synthesis, thereby diminishing the biofilm formation capacity of S. suis. Additionally, the downregulation of adhesion gene expression due to luxS gene deletion was found to be independent of the monosaccharide medias of S. suis.

生物膜是猪链球菌(S. suis)引起持续感染的主要原因。新陈代谢和AI-2法定人数感应与猪链球菌生物膜的形成密切相关。虽然有报道称AI-2法定人数感应luxS基因在猪链球菌生物膜中发挥作用,但其具体的调控机制仍不清楚。本研究探讨了野生型(WT)、luxS突变体(ΔluxS)和互补株(CΔluxS)之间在生物膜形成和单糖代谢方面的差异,并利用Galleria mellonella幼虫研究了luxS基因缺失对鼠伤寒杆菌在不同单糖介质中毒力的影响。结果表明,缺失luxS基因会进一步损害猪链球菌的单糖代谢,影响其在以果糖、半乳糖、鼠李糖和甘露糖为唯一碳源的培养基中的生长。然而,在含有葡萄糖和 N-乙酰葡糖胺的培养基中没有观察到明显的影响。这种缺失也会削弱 EPS 的合成,从而降低猪链球菌的生物膜形成能力。此外,研究还发现,luxS 基因缺失导致的粘附基因表达下调与 S. suis 的单糖介质无关。
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引用次数: 0
β-enaminoester derivatives exhibit promising in vitro and in silico antiviral potential against Mayaro virus β-烯酰胺酯衍生物在体外和硅学中对马雅洛病毒表现出良好的抗病毒潜力
IF 2.3 3区 生物学 Q3 MICROBIOLOGY Pub Date : 2024-09-18 DOI: 10.1007/s00203-024-04135-9
Natasha Cristina da Rocha, Leonardo dos Santos Corrêa Amorim, Vitor Won-Held Rabelo, Carolina Oliveira da Silva, Luciene Soares Silva, Geicy Kelly Pires Barboza, Mariana Falcão Lopes Princisval Carlos, Aurea Echevarria Aznar Neves Lima, Izabel Christina Nunes de Palmer Paixão

Mayaro virus (MAYV) is the causative agent of Mayaro fever, which is characterized mainly by acute fever and long-term severe arthralgia, common manifestations of other arbovirus infections, making the correct diagnosis a challenge. Besides, MAYV infections have been reported in South America, especially in Brazil. However, the lack of vaccines or specific antiviral drugs to control these infections makes the search for new antivirals an urgent need. Herein, we evaluated the antiviral potential of synthetic β-enaminoesters derivatives against MAYV replication and their pharmacokinetic and toxicological (ADMET) properties using in vitro and in silico strategies. For this purpose, Vero cells were infected with MAYV at an MOI of 0.1, treated with compounds (50 µM) for 24 h, and virus titers were quantified by plaque reduction assays. Compounds 2b (83.33%) and 2d (77.53%) exhibited the highest activity with inhibition rates of 83.33% and 77.53%, respectively. The most active compounds 2b (EC50 = 18.92 µM; SI > 52.85), and 2d (EC50 = 14.52 µM; SI > 68.87) exhibited higher potency and selectivity than the control drug suramin (EC50 = 38.97 µM; SI > 25.66). Then, we investigated the mechanism of action of the most active compounds. None of the compounds showed virucidal activity, neither inhibited virus adsorption, but compound 2b inhibited virus entry (62.64%). Also, compounds 2b and 2d inhibited some processes involved with the release of new virus particles. Finally, in silico results indicated good ADMET parameters of the most active compounds and reinforced their promising profile as drug candidates against MAYV.

玛雅罗病毒(MAYV)是玛雅罗热的病原体,其主要特征是急性发热和长期严重关节痛,这是其他虫媒病毒感染的常见表现,因此正确诊断是一项挑战。此外,在南美洲,尤其是巴西,也有马雅洛热病毒感染的报道。然而,由于缺乏疫苗或特异性抗病毒药物来控制这些感染,因此迫切需要寻找新的抗病毒药物。在此,我们采用体外和硅学策略评估了合成β-烯酰胺酯衍生物对 MAYV 复制的抗病毒潜力及其药代动力学和毒理学(ADMET)特性。为此,用 MOI 为 0.1 的 MAYV 感染 Vero 细胞,用化合物(50 µM)处理 24 小时,并通过斑块还原测定法量化病毒滴度。化合物 2b (83.33%) 和 2d (77.53%) 的活性最高,抑制率分别为 83.33% 和 77.53%。活性最高的化合物 2b(EC50 = 18.92 µM;SI >;52.85)和 2d(EC50 = 14.52 µM;SI >;68.87)比对照药物舒拉明(EC50 = 38.97 µM;SI >;25.66)表现出更高的效力和选择性。然后,我们研究了最活跃化合物的作用机制。所有化合物都没有杀病毒活性,也没有抑制病毒的吸附,但化合物 2b 抑制了病毒的进入(62.64%)。此外,化合物 2b 和 2d 还抑制了与新病毒颗粒释放有关的一些过程。最后,硅学研究结果表明,最有活性的化合物具有良好的 ADMET 参数,这增强了它们作为抗 MAYV 候选药物的前景。
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引用次数: 0
Alternative agar substitutes for culturing unculturable microorganisms 培养不可培养微生物的琼脂替代品
IF 2.3 3区 生物学 Q3 MICROBIOLOGY Pub Date : 2024-09-17 DOI: 10.1007/s00203-024-04139-5
K. Demin, E. Prazdnova, M. Kulikov, M. Mazanko, A. Gorovtsov

Gelling agents are necessary for the preparation of solid or semisolid media. For more than a hundred years, agar has been the primary gelling agent. However, a substantial body of evidence has accumulated suggesting that agar-based media inhibit the growth of many microbial species through the generation of reactive oxygen species (ROS), toxic organic contaminants, or competitive exclusion effects. In this review we have compiled the largest amount of data to date on the use of various gelling agents in microbial isolation and cultivation, with the particular emphasis on rare microbe isolation cases. Our analysis suggested that microbial-derived compounds (especially gellan gum), as gelling agents, are superior to agar in their ability to isolate and maintain either new or known microbial species. We analyzed the reasons behind this success and concluded that there are phylum-level differences in microbial responses to the changes in conditions from natural to the laboratory conditions (with respect to gelling agent usage). Consequently, we hypothesize that at least partial success of microbial-derived gelling agents lies in the recreation of the natural microenvironment conditions (which we address as the “familiarity of conditions” hypothesis). Finally, we present a list of recommendations and suggestions for further microbial ecology studies.

胶凝剂是制备固体或半固体培养基所必需的。一百多年来,琼脂一直是主要的胶凝剂。然而,大量证据表明,琼脂基培养基会通过产生活性氧(ROS)、有毒有机污染物或竞争排斥效应来抑制多种微生物的生长。在本综述中,我们汇编了迄今为止有关在微生物分离和培养中使用各种胶凝剂的最大量数据,并特别强调了罕见微生物分离案例。我们的分析表明,微生物衍生化合物(尤其是结冷胶)作为胶凝剂,在分离和维持新的或已知微生物物种的能力方面优于琼脂。我们分析了这一成功背后的原因,并得出结论:从自然条件到实验室条件(关于胶凝剂的使用)的变化,微生物的反应存在门级差异。因此,我们假设,微生物衍生胶凝剂的成功至少部分取决于自然微环境条件的再创造(我们将其称为 "条件熟悉性 "假设)。最后,我们为进一步的微生物生态学研究提出了一系列建议和意见。
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引用次数: 0
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Archives of Microbiology
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