阿斯珀吉洛马拉斯明A克服了金属β-乳糖酶抗生素耐药性的作用
Andrew M King1, Sarah A Reid-Yu2, Wenliang Wang3
11] M.G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario L8S 4K1, Canada [2] Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
Nature
|June 27, 2014
概括
一种新的真菌化合物阿斯伯吉洛马拉斯A (AMA) 有效地抑制金属β-乳酸酶 (MBLs). AMA恢复了对耐药格拉姆阴性病原体的卡巴胺抗生素的有效性,提供了潜在的新疗法.
科学领域:
- 微生物学 微生物学
- 传染性疾病 传染性疾病
- 药物发现 药物发现 药物发现
背景情况:
- 耐卡巴胺的格拉姆阴性病原体对全球健康构成重大威胁.
- 金属β-乳酸酶 (MBLs),像NDM-1,是关键的酶赋予耐药性至关重要的抗生素.
- 现有的治疗方法是有限的,因为广泛的耐药性.
研究的目的:
- 为了确定MBL酶的新型抑制剂.
- 评估这些抑制剂在恢复抗生素对抗耐药细菌的活性方面的潜力.
- 在临床前模型中评估治疗疗效.
主要方法:
- 查真菌天然产品的MBL抑制活性.
- 生物化学测试以确定酶抑制功效.
- 在实验室测试抗生素再敏感性在耐药的阴性细菌.
- 在小鼠感染模型中的体内疗效研究.
主要成果:
- 阿斯伯吉洛马拉斯A (AMA) 被确定为NDM-1和VIM-2MBLs的强有力的抑制剂.
- 亚马恢复了对各种格拉姆阴性病原体的美罗胺活性,包括肠杆菌,阿辛托巴克特菌种类和伪杆菌种类.
- 与AMA和美罗的联合治疗在Klebsiella肺炎感染的小鼠模型中显示出治疗潜力.
结论:
- 阿斯珀吉洛马拉斯A是一种有前途的MBL抑制剂,具有对抗卡巴胺耐药性的潜力.
- 亚马可以使抗卡巴胺的抗性格拉姆阴性病原体重新敏感.
- 联合治疗AMA和卡巴胺为治疗由MBL产生细菌引起的感染提供了一种可行的策略.
相关概念视频
01:25Mechanism of Antibiotic Resistance in MRSA
211
Antibiotic resistance in bacteria arises when microorganisms evolve the ability to withstand drugs designed to kill them or inhibit their growth, rendering once-effective treatments useless. This phenomenon, driven by genetic change and selection under antibiotic exposure, poses a profound threat to modern medicine. Mechanisms include drug-inactivating enzymes (e.g., β-lactamases), efflux pumps that eject antibiotics, mutations altering antibiotic targets, decreased drug uptake, and...
211
01:30Development of Antibiotic Resistance
2.0K
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...
2.0K
01:25Clinical Significance of Antibiotic Resistance
85
Methicillin-resistant Staphylococcus aureus (MRSA) presents a critical public health threat, arising from its capacity to resist β-lactam antibiotics due to acquisition of the mecA gene within the staphylococcal cassette chromosome mec (SCCmec). This gene encodes penicillin-binding protein 2a (PBP2a), which impairs binding efficacy of methicillin and other β-lactams. MRSA has evolved into distinct clonal lineages impacting humans and animals alike, reinforcing its significance within...
85
00:57Antibiotic Selection
48.8K
Overview
48.8K
01:28Antimicrobial Effectiveness
2.3K
The effectiveness of antimicrobial agents depends on various factors influencing their ability to eliminate microbial populations. Larger microbial populations require more time for complete eradication, emphasizing the importance of population size analysis when evaluating antimicrobial efficacy.Microbial resistance to antimicrobial agents varies significantly. Highly resilient microorganisms include endospores, gram-negative bacteria, and non-enveloped viruses, while prions are exceptionally...
2.3K
01:25Inhibitors of Bacterial Protein Synthesis
102
Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, specifically disrupting protein synthesis. These polycationic molecules consist of amino-modified sugars linked via glycosidic bonds to an aminocyclitol core such as 2-deoxystreptamine or streptamine. Their strong positive charges facilitate tight binding to the negatively charged phosphate backbone of ribosomal RNA (rRNA), primarily at the 16S...
102