PDF(Pubmed)
Abstract：
UNASSIGNED: Multidrug resistance in bacteria is a pressing concern, particularly among clinical isolates. Gram-negative bacteria like Salmonella employ various strategies, such as altering membrane properties, to resist treatment. Their two-membrane structure affects susceptibility to antibiotics, whereas specific proteins and the peptidoglycan layer maintain envelope integrity. Disruptions can compromise stability and resistance profile toward xenobiotics. In this study, we investigated the unexplored protein SanA\'s role in modifying bacterial membranes, impacting antibiotic resistance, and intracellular replication within host cells.
UNASSIGNED: We generated a sanA deletion mutant and complemented it in trans to assess its biological function. High-throughput phenotypic profiling with Biolog Phenotype microarrays was conducted using 240 xenobiotics. Membrane properties and permeability were analyzed via cytochrome c binding, hexadecane adhesion, nile red, and ethidium bromide uptake assays, respectively. For intracellular replication analysis, primary bone marrow macrophages served as a host cells model.
UNASSIGNED: Our findings demonstrated that the absence of sanA increased membrane permeability, hydrophilicity, and positive charge, resulting in enhanced resistance to certain antibiotics that target peptidoglycan synthesis. Furthermore, the sanA deletion mutant demonstrated enhanced replication rates within primary macrophages, highlighting its ability to evade the bactericidal effects of the immune system. Taking together, we provide valuable insights into a poorly known SanA protein, highlighting the complex interplay among bacterial genetics, membrane physiology, and antibiotic resistance, underscoring its significance in understanding Salmonella pathogenicity.
UNASSIGNED: We generated a sanA deletion mutant and complemented it in trans to assess its biological function. High-throughput phenotypic profiling with Biolog Phenotype microarrays was conducted using 240 xenobiotics. Membrane properties and permeability were analyzed via cytochrome c binding, hexadecane adhesion, nile red, and ethidium bromide uptake assays, respectively. For intracellular replication analysis, primary bone marrow macrophages served as a host cells model.
UNASSIGNED: Our findings demonstrated that the absence of sanA increased membrane permeability, hydrophilicity, and positive charge, resulting in enhanced resistance to certain antibiotics that target peptidoglycan synthesis. Furthermore, the sanA deletion mutant demonstrated enhanced replication rates within primary macrophages, highlighting its ability to evade the bactericidal effects of the immune system. Taking together, we provide valuable insights into a poorly known SanA protein, highlighting the complex interplay among bacterial genetics, membrane physiology, and antibiotic resistance, underscoring its significance in understanding Salmonella pathogenicity.
摘要：
■细菌中的多药耐药性是一个紧迫的问题，特别是在临床分离物中。革兰氏阴性细菌如沙门氏菌采用各种策略，例如改变膜的性质，抵制治疗。它们的双膜结构影响对抗生素的敏感性，而特定的蛋白质和肽聚糖层保持包膜完整性。破坏会损害稳定性和对外源性物质的抗性。在这项研究中,我们调查了未开发的蛋白质SanA在修饰细菌膜中的作用，影响抗生素耐药性，和宿主细胞内的细胞内复制。
■我们生成了一个sanA缺失突变体，并对其进行反式互补，以评估其生物学功能。使用Biolog表型微阵列的高通量表型分析使用240种异生物剂进行。通过细胞色素C结合分析膜特性和通透性，十六烷附着力，尼罗河红,和溴化乙锭摄取测定，分别。对于细胞内复制分析，原代骨髓巨噬细胞作为宿主细胞模型。
■我们的研究结果表明，没有sanA会增加膜的通透性，亲水性,和正电荷，导致对某些靶向肽聚糖合成的抗生素的抗性增强。此外，sanA缺失突变体在原代巨噬细胞内表现出增强的复制率，强调其逃避免疫系统杀菌作用的能力。一起,我们提供了一种鲜为人知的SanA蛋白的宝贵见解，强调细菌遗传学之间复杂的相互作用，膜生理学，和抗生素耐药性，强调其在了解沙门氏菌致病性方面的重要性。
■我们生成了一个sanA缺失突变体，并对其进行反式互补，以评估其生物学功能。使用Biolog表型微阵列的高通量表型分析使用240种异生物剂进行。通过细胞色素C结合分析膜特性和通透性，十六烷附着力，尼罗河红,和溴化乙锭摄取测定，分别。对于细胞内复制分析，原代骨髓巨噬细胞作为宿主细胞模型。
■我们的研究结果表明，没有sanA会增加膜的通透性，亲水性,和正电荷，导致对某些靶向肽聚糖合成的抗生素的抗性增强。此外，sanA缺失突变体在原代巨噬细胞内表现出增强的复制率，强调其逃避免疫系统杀菌作用的能力。一起,我们提供了一种鲜为人知的SanA蛋白的宝贵见解，强调细菌遗传学之间复杂的相互作用，膜生理学，和抗生素耐药性，强调其在了解沙门氏菌致病性方面的重要性。
