效流基因放大绕过了对抗双向抗生素耐药性的多个标突变的必要性
Kalinga Pavan T Silva1, Ganesh Sundar1, Anupama Khare2
1Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Nature communications
|June 9, 2023
概括
耐甲基西林黄金葡萄球菌 (MRSA) 可以通过排泄SdrM快速发展对多向抗生素delafloxacin (DLX) 的高耐药性. 这绕过了目标突变,增加了耐药性演变的频率.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 预计具有多个细胞点的抗生素可以减少耐药性演变.
- 然而,对这种药物的适应性轨迹和抵抗机制仍未得到充分研究.
- 甲素耐药黄金葡萄球菌 (MRSA) 是一个重要的公共卫生问题.
研究的目的:
- 调查MRSA.中对delafloxacin (DLX) 的耐药性演变和机制.
- 了解排泄在抗生素耐药性中的作用.
- 评估在临床隔离物中发现的耐药性机制的普遍性.
主要方法:
- 暴露于DLX的MRSA的实验演变.
- 基因组分析以确定突变和放大.
- 评估排泄基因表达和功能.
主要成果:
- 高DLX耐药性是通过SdrM排泄的突变或过度表达而演变的.
- 由基因组放大驱动的SdrM过度表达绕过了对酶突变的需要.
- 由于联合放大的排泄,出现了链杆菌素交叉耐药性.
- SdrM促进了较高频率的DLX抗性演变.
- 在不同的临床MRSA单独体中观察到相同的SdrM介导的耐药性机制.
结论:
- 对DLX等多向抗生素的耐药性可以通过高频替代途径演变.
- 排泄SdrM在MRSA中迅速发展DLX耐药性方面发挥着至关重要的作用.
- 鉴定出的抗药性机制是一般性的,与临床环境相关,突出显示了抗生素治疗中的潜在挑战.
相关概念视频
Development of Antibiotic Resistance
50
Antibiotic resistance is a major public health concern that arises when bacteria evolve mechanisms to withstand the effects of antibiotic treatments. This resistance can be intrinsic, acquired through genetic mutations, or transferred between bacteria via horizontal gene transfer. The development of antibiotic resistance poses significant challenges in treating bacterial infections and necessitates ongoing research to develop new therapeutic strategies.Intrinsic resistance occurs when bacterial...
50
Antibiotic Selection
54.8K
Overview
54.8K
Gene Regulation in Microbial Communities: Quorum Sensing
51
Quorum sensing is a mechanism of bacterial communication that enables coordinated gene expression in response to changes in population density. This facilitates collective behaviors that enhance survival, resource acquisition, and ecological adaptation. This process relies on small signaling molecules called autoinducers that accumulate as bacterial populations grow. When a critical threshold concentration of autoinducers is reached, bacterial cells collectively modify gene expression,...
51
Treatment Resistant Cancers
3.4K
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.4K
Carrier-Mediated Transport
474
Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
474
Transduction
49
Among the three main modes of HGT—transformation, conjugation, and transduction—transduction is unique in that it is mediated by bacteriophages, or bacterial viruses.Transduction occurs in two ways. Generalized transduction occurs during the lytic cycle of a bacteriophage infection. In this process, bacteriophages infect bacterial cells, replicate within them, and ultimately cause cell lysis, releasing newly assembled virions. Occasionally, random fragments of the bacterial genome...
49


