氨基甘油酸抗生素诱导细菌生物膜的形成
Lucas R Hoffman1, David A D'Argenio, Michael J MacCoss
1Department of Pediatrics, University of Washington, Seattle, Washington 98195, USA.
Nature
|August 27, 2005
概括
亚致命的氨基甘油酸抗生素会在Pseudomonas aeruginosa等细菌中触发生物膜的形成. 一个新发现的基因,氨基糖化物反应调节器 (arr),对于这一过程至关重要,并增强了抗生素耐药性.
科学领域:
- 微生物学 微生物学
- 细菌病原体的产生
- 药物耐药性 药物耐药性 药物耐药性
背景情况:
- 细菌生物膜是耐抗生素治疗的持续性社区,有助于慢性感染.
- 了解生物膜形成机制对于治疗持续性细菌感染至关重要,例如囊性纤维化患者的Pseudomonas aeruginosa.
研究的目的:
- 调查氨基糖化抗生素的亚抑制度如何影响细菌中的生物膜形成.
- 确定参与抗生素诱导生物膜形成的遗传因素和分子途径.
主要方法:
- 对 Pseudomonas aeruginosa 和 Escherichia coli 暴露于亚抑制性氨基糖化物度.
- 在P. aeruginosa.中发现的"氨基糖化物反应调节器" (arr) 基因的遗传分析.
- 在细菌膜中测量循环二氨酸单酸盐 (c-di-GMP) 固酶活性.
- 评估生物膜形成对托布拉米辛的反应和GTP的抑制.
主要成果:
- 抑制性氨基甘油酸抗生素诱导P. aeruginosa和E. coli中的生物膜形成.
- "氨基糖体反应调节器" (arr) 基因对于这种诱导至关重要,并赋予生物膜特异性耐药性.
- Arr编码了一个c-di-GMP化酶,arr突变体显示化酶活性降低.
- 托布拉米辛诱导的生物膜形成是由c-di-GMP水平的变化介导的.
结论:
- 细菌生物膜的形成可能是对抗生素存在的防御反应.
- 在这种抗生素诱导的生物膜形成中,arr基因和循环二氨单酸盐 (c-di-GMP) 水平的调节是关键.
- 这一发现为对抗慢性细菌感染提供了潜在的新目标.
相关概念视频
01:18Surface Membrane Barriers
The skin and mucous membranes serve as the primary line of defense against pathogens by providing both physical and chemical protection. These barriers are essential in preventing the entry and establishment of microbes, thereby maintaining the integrity of the host.
The outer layer of the skin, the epidermis, is a robust barrier comprising layers of closely packed keratinized cells. This dense arrangement prevents microbes from penetrating the body. The periodic shedding of epidermal cells...
The outer layer of the skin, the epidermis, is a robust barrier comprising layers of closely packed keratinized cells. This dense arrangement prevents microbes from penetrating the body. The periodic shedding of epidermal cells...
01:23Antimicrobial Proteins
Antimicrobial proteins are important components of the immune system. They aid the body in combating pathogens by either killing them directly or hindering their replication processes. Four main types of antimicrobial substances are interferons, the complement system, iron-binding proteins, and antimicrobial proteins.
Interferons
Interferons (IFNs) are proteins produced by lymphocytes, macrophages, and fibroblasts infected with viruses. While IFNs cannot prevent viruses from entering and...
Interferons
Interferons (IFNs) are proteins produced by lymphocytes, macrophages, and fibroblasts infected with viruses. While IFNs cannot prevent viruses from entering and...
01:29Biosynthesis of Lipids
Microbial membranes exhibit remarkable diversity in lipid composition, reflecting evolutionary adaptations to various environmental conditions. The three domains of life—Bacteria, Archaea, and Eukarya—synthesize membrane lipids through distinct biosynthetic pathways, leading to fundamental structural differences that impact membrane stability, function, and adaptability.Fatty Acid-Based Lipids in Bacteria and EukaryaBacteria and eukaryotes share a common fatty acid biosynthesis pathway, which...
01:19Formation of Lipopolysaccharides
Lipopolysaccharides (LPS) are crucial components of the outer membrane of Gram-negative bacteria, serving both structural and functional roles. It contributes to membrane stability and protects bacteria from host immune responses. LPS is composed of three major regions—lipid A, a core oligosaccharide, and an O antigen. The biosynthesis and assembly of LPS involve a highly coordinated set of enzymatic reactions and transport mechanisms. Additionally, LPS is recognized as an endotoxin, triggering...
01:29Staphylococcal Skin Infections
Staphylococcus aureus is a Gram-positive coccus that resides harmlessly on the skin and mucous membranes of healthy individuals. When the skin barrier is breached, it can shift from a commensal to an opportunistic pathogen. This transition is facilitated by surface adhesins, such as clumping factor B and S. aureus surface protein G (SasG), which bind to structural proteins, including loricrin and cytokeratin, in the damaged epidermis. Protein A, another key factor, binds the Fc region of...
01:23Inhibitors of Gram-positive Cell Wall Synthesis
Bacterial cell walls are typically rigid structures composed mainly of peptidoglycan, a mesh-like polymer that provides mechanical strength and maintains cell shape. The synthesis of peptidoglycan is a crucial process in bacterial growth and serves as a primary target for many antibiotics.Mechanism of Action of Beta-Lactam AntibioticsBeta-lactam antibiotics, such as penicillin, inhibit peptidoglycan synthesis in actively growing cells. These antibiotics share a characteristic four-membered...