Large-Scale Chemical-Genetic Strategy Enables the Design of Antimicrobial Combination Chemotherapy in Mycobacteria. 切换为中文 Abstract: :The efficacies of all antibiotics against tuberculosis are eventually eroded by resistance. New strategies to discover drugs or drug combinations with higher barriers to resistance are needed. Previously, we reported the application of a large-scale chemical-genetic interaction screening strategy called PROSPECT (PRimary screening Of Strains to Prioritize Expanded Chemistry and Targets) for the discovery of new Mycobacterium tuberculosis inhibitors, which resulted in the identification of the small molecule BRD-8000, an inhibitor of a novel target, EfpA [ Johnson et al. ( 2019 ) Nature 517 , 72 ]. Leveraging the chemical genetic interaction profile of BRD-8000, we identified BRD-9327, another structurally distinct small molecule EfpA inhibitor. We show that the two compounds are synergistic and display collateral sensitivity because of their distinct modes of action and resistance mechanisms. High-level resistance to one increases the sensitivity to and reduces the emergence of resistance to the other. Thus, the combination of BRD-9327 and BRD-8000 represents a proof-of-concept for the novel strategy of leveraging chemical genetics in the design of antimicrobial combination chemotherapy in which mutual collateral sensitivity is exploited. About the Journal ACS Infectious Diseases is the first journal to highlight chemistry and its role in the multidisciplinary and collaborative field of infectious disease research. The scope of the journal encompasses all aspects of chemistry relating to infectious diseases research including research on pathogens, host-pathogen interactions, therapeutics, diagnostics, vaccines, drug-delivery systems, and other biomedical technology development pertaining to infectious diseases. With editors well-versed in both chemistry and the biology of infectious diseases, the journal aims to bridge the gap between these two disciplines. ACS Infectious Diseases welcomes submission of articles with a balance of chemistry and biology, and encourages discussions centered on specific pathogen- and disease-related issues. Journal Scope Topics covered by the journal include but are not limited to the following: Pathogens and Host-Pathogen Interactions Use of structural biology, chemical biology, glycobiology, physical chemistry, nucleic acid chemistry, and biochemistry to elucidate molecular mechanisms of pathogenesis Development of tools to dissect mechanisms of pathogenesis Therapeutics Use of target-, phenotypic-, or computational-based approaches for discovery and development of new agents to treat infectious diseases, with an emphasis on establishing mechanism of action, understanding binding mode and inhibitory mechanism, and/or discussing pathogen-specific challenges to drug development Development of new technologies to facilitate characterization, validation, and prioritization of potential drug targets or to assess the physicochemical bases for cellular penetration of anti-infectives Mechanistic investigations of antimicrobial resistance Vaccines Discovery and development of synthetic vaccines and small molecule vaccine adjuvants Structural, physical, or computational investigations of epitope binding Diagnostics Development of novel and improved diagnostics using physical, surface, analytical, and nano chemistry techniques Use of structural biology, molecular biology, and chemical biology to investigate diagnostics targets Drug Delivery Systems Use of novel materials and technologies, such as nanotechnologies, for delivery of antimicrobial agents 中文简介：（来自Google、百度翻译） 关于杂志 ACS传染病是第一本强调化学及其在传染病研究的多学科和协作领域中的作用的杂志。该杂志的范围包括与传染病研究有关的化学的所有方面，包括对病原体的研究、宿主与病原体的相互作用、治疗学、诊断学、疫苗、药物输送系统以及与传染病有关的其他生物医学技术的发展。 编辑们精通传染病的化学和生物学，该杂志旨在弥合这两门学科之间的鸿沟。ACS传染病欢迎提交化学和生物学平衡的文章，并鼓励围绕特定病原体和疾病相关问题进行讨论。 该期刊涵盖的主题包括但不限于以下内容: 病原体与宿主-病原体相互作用 运用结构生物学、化学生物学、糖生物学、物理化学、核酸化学、生物化学等，阐明发病的分子机制 发展工具解剖发病机制 利用目标、表型或基于计算的方法发现和开发治疗传染病的新制剂，重点是建立作用机制、理解结合模式和抑制机制，以及/或讨论药物开发面临的病原体特异性挑战 开发新技术，以促进对潜在药物靶点的鉴定、验证和优先排序，或评估抗感染药物的细胞渗透的物理化学基础 抗菌素耐药性的机制研究 合成疫苗和小分子疫苗佐剂的发现和开发 表位结合的结构、物理或计算研究 利用物理、表面、分析和纳米化学技术开发新的和改进的诊断方法 利用结构生物学、分子生物学和化学生物学研究诊断目标 药物输送系统 利用新材料和新技术，如纳米技术，来运送抗菌药物 杂志主要接受有关抗感染类研究的生物学与化学生物学的文章，对文章水平要求高。我投稿后已经接受了，两个月不到给了修改意见，就十几条，小修，认真回答，投回两周校稿顺利接收。 2019-08-04 Cancer Immunology Research... 影响因子：11.151 ISSN：2326-6066 研究方向：ONCOLOGY-IMMUNOLOGY Infectious Agents and Cancer... 影响因子：2.965 ISSN：1750-9378 研究方向：ONCOLOGY-IMMUNOLOGY INTEGRATIVE CANCER THERAPIES... 影响因子：3.279 ISSN：1534-7354 研究方向：医学-全科医学与补充医学 Hormones & Cancer... 影响因子：3.869 ISSN：1868-8497 研究方向：ONCOLOGY-ENDOCRINOLOGY & METABOLISM Turk hijiyen ve deneysel biyoloji dergisi. Turkish bulletin of hygiene and experimental biology

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