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SARS-CoV-2 Resistance to Small Molecule Inhibitors. SARS-CoV-2 对小分子抑制剂的抗药性。
IF 3.1 Q2 MICROBIOLOGY Pub Date : 2024-09-01 Epub Date: 2024-06-24 DOI: 10.1007/s40588-024-00229-6
Uxua Modrego Lopez, Md Mehedi Hasan, Brandon Havranek, Shahidul M Islam

Purpose of the review: SARS-CoV-2 undergoes genetic mutations like many other viruses. Some mutations lead to the emergence of new Variants of Concern (VOCs), affecting transmissibility, illness severity, and the effectiveness of antiviral drugs. Continuous monitoring and research are crucial to comprehend variant behavior and develop effective response strategies, including identifying mutations that may affect current drug therapies.

Recent findings: Antiviral therapies such as Nirmatrelvir and Ensitrelvir focus on inhibiting 3CLpro, whereas Remdesivir, Favipiravir, and Molnupiravir target nsp12, thereby reducing the viral load. However, the emergence of resistant mutations in 3CLpro and nsp12 could impact the efficiency of these small molecule drug therapeutics.

Summary: This manuscript summarizes mutations in 3CLpro and nsp12, which could potentially reduce the efficacy of drugs. Additionally, it encapsulates recent advancements in small molecule antivirals targeting SARS-CoV-2 viral proteins, including their potential for developing resistance against emerging variants.

审查的目的:与许多其他病毒一样,SARS-CoV-2 也会发生基因突变。有些变异会导致新的关注变异体(VOC)的出现,影响传播性、疾病严重程度和抗病毒药物的有效性。持续监测和研究对于理解变异行为和制定有效的应对策略至关重要,包括确定可能影响当前药物疗法的变异:最近的研究结果:Nirmatrelvir 和 Ensitrelvir 等抗病毒疗法主要抑制 3CLpro,而 Remdesivir、Favipiravir 和 Molnupiravir 则针对 nsp12,从而降低病毒载量。然而,3CLpro 和 nsp12 耐药突变的出现可能会影响这些小分子药物疗法的疗效。摘要:本手稿总结了 3CLpro 和 nsp12 的突变,这些突变可能会降低药物的疗效。此外,它还概括了针对 SARS-CoV-2 病毒蛋白的小分子抗病毒药物的最新进展,包括它们对新出现的变体产生抗药性的可能性。
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引用次数: 0
Integrating Genomic Data with the Development of CRISPR-Based Point-of-Care-Testing for Bacterial Infections. 将基因组数据与开发基于 CRISPR 的细菌感染护理点检测相结合。
IF 3.1 Q2 MICROBIOLOGY Pub Date : 2024-01-01 Epub Date: 2024-10-15 DOI: 10.1007/s40588-024-00236-7
Thanyapat Wanitchanon, Claire Chewapreecha, Chayasith Uttamapinant

Purpose of review: Bacterial infections and antibiotic resistance contribute to global mortality. Despite many infections being preventable and treatable, the lack of reliable and accessible diagnostic tools exacerbates these issues. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-based diagnostics has emerged as a promising solution. However, the development of CRISPR diagnostics has often occurred in isolation, with limited integration of genomic data to guide target selection. In this review, we explore the synergy between bacterial genomics and CRISPR-based point-of-care tests (POCT), highlighting how genomic insights can inform target selection and enhance diagnostic accuracy.

Recent findings: We review recent advances in CRISPR-based technologies, focusing on the critical role of target sequence selection in improving the sensitivity of CRISPR-based diagnostics. Additionally, we examine the implementation of these technologies in resource-limited settings across Asia and Africa, presenting successful case studies that demonstrate their potential.

Summary: The integration of bacterial genomics with CRISPR technology offers significant promise for the development of effective point-of-care diagnostics.

审查目的:细菌感染和抗生素耐药性导致全球死亡率上升。尽管许多感染是可以预防和治疗的,但由于缺乏可靠和方便的诊断工具,这些问题变得更加严重。基于 CRISPR(Clustered Regularly Interspaced Short Palindromic Repeats)的诊断方法已成为一种前景广阔的解决方案。然而,CRISPR 诊断技术的开发往往是孤立进行的,对基因组数据的整合有限,无法指导目标选择。在这篇综述中,我们探讨了细菌基因组学与基于CRISPR的床旁检测(POCT)之间的协同作用,重点介绍了基因组学见解如何为目标选择提供信息并提高诊断准确性:我们回顾了基于 CRISPR 的技术的最新进展,重点关注目标序列选择在提高基于 CRISPR 的诊断灵敏度方面的关键作用。摘要:细菌基因组学与 CRISPR 技术的整合为开发有效的护理点诊断技术带来了巨大的希望。
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引用次数: 0
Intimate Relationship Between Stress and Human Alpha‑Herpes Virus 1 (HSV‑1) Reactivation from Latency. 应激与人类甲型疱疹病毒1型(HSV-1)潜伏期再激活的密切关系
IF 5.2 Q2 MICROBIOLOGY Pub Date : 2023-12-01 Epub Date: 2023-07-27 DOI: 10.1007/s40588-023-00202-9
Clinton Jones

Purpose of review: Numerous studies concluded stress (acute, episodic acute, or chronic) increases the incidence of human alpha-herpes virus 1 (HSV-1) reactivation from latency in neurons. This review will summarize how stress stimulates viral gene expression, replication, and reactivation from latency.

Recent findings: Stress (capital S) stress-mediated activation of the glucocorticoid receptor (GR) accelerates reactivation from latency, whereas a corticosteroid-specific antagonist impairs viral replication and reactivation from latency. GR and specific stress-induced cellular transcription factors also stimulate viral promoters that drive expression of key viral transcriptional regulators: infected cell protein 0 (ICP0), ICP4, ICP27 and viral tegument protein (VP16). Hence, GR is predicted to initially stimulate viral gene expression. GR-mediated immune-inhibitory functions are also predicted to enhance viral replication and viral spread.

Summary: Identifying cellular factors and viral regulatory proteins that trigger reactivation from latency in neurons may provide new therapeutic strategies designed to reduce the incidence of reactivation from latency.

综述的目的:大量研究认为,压力(急性、偶发性急性或慢性)会增加人类α-疱疹病毒1(HSV-1)从神经元潜伏期重新激活的发生率。本综述将总结压力是如何刺激病毒基因表达、复制和从潜伏期重新激活的:最近的研究发现:应激(大写字母 S)介导的糖皮质激素受体(GR)激活可加速潜伏期病毒的重新激活,而皮质激素特异性拮抗剂则会损害病毒复制和潜伏期病毒的重新激活。GR和特定压力诱导的细胞转录因子也会刺激病毒启动子,从而驱动关键病毒转录调节因子的表达:感染细胞蛋白0(ICP0)、ICP4、ICP27和病毒外壳蛋白(VP16)。因此,预计 GR 最初会刺激病毒基因的表达。小结:确定引发神经元潜伏期再活化的细胞因素和病毒调控蛋白可能会提供新的治疗策略,以降低潜伏期再活化的发生率。
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引用次数: 0
Bacterial and Fungal Keratitis: Current Trends in Its Diagnosis and Management 细菌性和真菌性角膜炎:诊断和管理的当前趋势
IF 5.2 Q2 MICROBIOLOGY Pub Date : 2023-11-15 DOI: 10.1007/s40588-023-00210-9
Surya Prakash Sharma, Sujata Dwivedi, Sunil Kumar, K. Dhama, A. K. Sharma
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引用次数: 0
Engineered Therapeutic Antibody Against SARS-CoV-2 针对SARS-CoV-2的工程化治疗性抗体
Q2 MICROBIOLOGY Pub Date : 2023-11-14 DOI: 10.1007/s40588-023-00212-7
Monrat Chulanetra
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引用次数: 0
Status of Drug Discovery in Wetlands Through a Lens of Bioprospecting for New Antimicrobials Being Produced by Microorganisms 从微生物产生的新型抗菌素的生物勘探角度看湿地药物发现的现状
Q2 MICROBIOLOGY Pub Date : 2023-11-08 DOI: 10.1007/s40588-023-00209-2
Bojana Stekovic, Karl Anderson, Delainey Lancaster, Evelyn Stuck, Tsebaot Getachew, Venugopal Mukku, Brian J. Dingmann
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引用次数: 0
Porin-Mediated Carbapenem Resistance in Klebsiella pneumoniae: an Alarming Threat to Global Health 肺炎克雷伯菌中孔蛋白介导的碳青霉烯耐药:对全球健康的惊人威胁
Q2 MICROBIOLOGY Pub Date : 2023-11-04 DOI: 10.1007/s40588-023-00211-8
Indrani Gogoi, Minakshi Puzari, Pankaj Chetia
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引用次数: 0
Molecular Mechanisms of HIV-1 Latency from a Chromatin and Epigenetic Perspective 从染色质和表观遗传学的角度看HIV-1潜伏期的分子机制
Q2 MICROBIOLOGY Pub Date : 2023-10-20 DOI: 10.1007/s40588-023-00208-3
Bianca B. Jütte, Luca Love, J. Peter Svensson
Abstract Purpose of Review The main obstacle to an HIV-1 cure is the reservoir of HIV-1 infected cells. While antiretroviral therapy (ART) eliminates the HIV-1 virus effectively, it does not target the reservoir. To eliminate infected cells, we need an improved understanding of the reservoir maintenance and reactivation mechanisms, including the influence of chromatin. Recent Findings The last years’ technological advances enable an in-depth study of the reservoir, uncovering subsets of infected cells, proviral integration sites, and single-cell nucleosome histone modifications. These revelations illustrate how the immune system and cell proliferation shape reservoirs under long-term ART. These forces create highly individual reservoirs that will require personalized treatment for their eradication. Summary A greater understanding of HIV-1 latency mechanisms, focusing on chromatin features, proviral reservoir dynamics, and inter-individual differences, can drive the development of more precise HIV-1 treatment strategies, ultimately achieving a globally available HIV-1 cure.
HIV-1治疗的主要障碍是HIV-1感染细胞的储存库。虽然抗逆转录病毒疗法(ART)可以有效地消除HIV-1病毒,但它并不针对病毒库。为了消除受感染的细胞,我们需要更好地了解储存库的维持和再激活机制,包括染色质的影响。近年来的技术进步使对病毒库的深入研究成为可能,揭示了感染细胞的亚群、原病毒整合位点和单细胞核小体组蛋白修饰。这些揭示说明了免疫系统和细胞增殖如何在长期抗逆转录病毒治疗下形成储库。这些力量产生了高度个性化的水库,需要个性化的治疗来消灭它们。更深入地了解HIV-1潜伏机制,重点关注染色质特征、前病毒库动力学和个体间差异,可以推动更精确的HIV-1治疗策略的发展,最终实现全球可用的HIV-1治愈。
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引用次数: 0
Gut Microbiota Resilience Mechanisms Against Pathogen Infection and its Role in Inflammatory Bowel Disease 肠道微生物群抗病原体感染的恢复机制及其在炎症性肠病中的作用
Q2 MICROBIOLOGY Pub Date : 2023-10-07 DOI: 10.1007/s40588-023-00207-4
Marcella Cipelli, Eloísa Martins da Silva, Niels Olsen Saraiva Câmara
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引用次数: 0
Symbiotic Interactions of Archaea in Animal and Human Microbiomes 古生菌在动物和人类微生物群中的共生相互作用
Q2 MICROBIOLOGY Pub Date : 2023-09-29 DOI: 10.1007/s40588-023-00204-7
Nancy Weiland-Bräuer
Abstract Purpose of Review Since the introduction of Archaea as a new domain of life more than 45 years ago, progress in their phylogenetic classification and knowledge of their exclusive biological characteristics has identified archaea as unique microorganisms which are widespread in extreme but also in various moderate ecosystems, including eukaryotic hosts. However, archaea are still neglected players within microbiomes, and research on archaea-bacteria interactions is still in its infancy due to methodological challenges. Recent Findings This review summarizes the current knowledge of archaea as components within microbiomes and focuses on their interactions with their bacterial neighbors and the principles of archaeal interactions. Summary Archaea are common constituents of animal and human microbiomes, which are dominated by Euryarchaeota. The gastrointestinal tract is the most studied body site, where archaea account for up to 4% of all microorganisms, primarily represented by methanogens. No archaeal pathogen has yet been identified, although methanogens are hypothesized to be indirectly involved in pathogenicity. Archaeal interactions comprise symbiotic relationships, and the cell membrane and wall might be as crucial as quorum sensing/quenching for these interactions. Particularly, syntrophic interactions under energy-deficiency stress seem to be an essential strategy for archaea. However, more research is urgently needed to discover how archaea sense their environment, compete with bacteria, and interact within complex microbiomes associated with multicellular organisms.
自古生菌作为一种新的生命领域被引入以来,随着其系统发育分类和对其特有生物学特性的了解的进展,古生菌作为一种独特的微生物广泛存在于极端生态系统中,但也存在于包括真核宿主在内的各种中等生态系统中。然而,古生菌仍然是微生物组中被忽视的参与者,由于方法上的挑战,古生菌与细菌相互作用的研究仍处于起步阶段。本文综述了古细菌作为微生物组的组成部分的现有知识,重点介绍了它们与邻近细菌的相互作用以及古细菌相互作用的原理。古生菌是动物和人类微生物群的共同组成部分,以Euryarchaeota为主。胃肠道是研究最多的身体部位,其中古生菌占所有微生物的4%,主要以产甲烷菌为代表。虽然假设产甲烷菌间接参与致病性,但尚未发现古细菌病原体。古菌相互作用包括共生关系,细胞膜和细胞壁可能对这些相互作用至关重要,就像群体感应/淬灭一样。特别是,能量缺乏胁迫下的共生相互作用似乎是古菌的基本策略。然而,迫切需要更多的研究来发现古细菌如何感知环境,与细菌竞争,以及在与多细胞生物相关的复杂微生物群中相互作用。
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Current Clinical Microbiology Reports
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