了解革兰氏阴性病原体鲍曼不动杆菌的抗菌药耐药性机制和潜在治疗方法。

IF 4.1 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY RSC medicinal chemistry Pub Date : 2024-09-19 DOI:10.1039/d4md00449c
Vishwani Jamwal, Tashi Palmo, Kuljit Singh
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引用次数: 0

摘要

在全球范围内,病原体抗微生物耐药性的出现已严重威胁到人类的健康和福祉。医院中由耐药微生物引起的感染与发病率、死亡率和医疗成本的增加有关。鲍曼不动杆菌(Acinetobacter baumannii)是一种革兰氏阴性细菌,属于 ESKAPE 菌群,广泛与医院内感染有关。它在医院中顽固存在,经抗生素治疗后仍能存活,引发急性感染,如尿路感染、肺炎、菌血症、脑膜炎和伤口相关感染。药物发现方面的创新空白以及缺乏针对鲍曼尼氏菌的新治疗措施,继续困扰着感染控制部门应对不断上升的耐药病例。耐药鲍曼尼氏菌菌株的出现也导致新发现的抗生素不断失效。因此,探索新策略是推动鲍曼不动杆菌药物研发的必要条件。本综述讨论了细菌研究界在鲍曼不动杆菌领域所做的努力,重点关注为确定有效支架和新靶点而采取的策略,以加强和丰富药物发现的化学空间。首先,我们讨论了现有的化疗方法和鲍曼不动杆菌菌株的各种抗微生物耐药机制。接下来,我们阐述了多学科方法和策略,这些方法和策略可能是应对当前耐药鲍曼不动杆菌菌株造成的威胁的出路。综述重点介绍了药物发现领域的最新进展,包括组合疗法、高通量筛选、药物再利用、纳米技术和抗微生物肽,这些都是未来对抗细菌病原体的必要工具。
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Understanding the mechanisms of antimicrobial resistance and potential therapeutic approaches against the Gram-negative pathogen Acinetobacter baumannii.

Globally, the emergence of anti-microbial resistance in pathogens has become a serious threat to human health and well-being. Infections caused by drug-resistant microorganisms in hospitals are associated with increased morbidity, mortality, and healthcare costs. Acinetobacter baumannii is a Gram-negative bacterium belonging to the ESKAPE group and is widely associated with nosocomial infections. It persists in hospitals and survives antibiotic treatment, prompting acute infections such as urinary tract infections, pneumonia, bacteremia, meningitis, and wound-related infections. An innovation void in drug discovery and the lack of new therapeutic measures against A. baumannii continue to afflict infection control against the rising drug-resistant cases. The emergence of drug-resistant A. baumannii strains has also led to the incessant collapse of newly discovered antibiotics. Therefore exploring novel strategies is requisite to give impetus to A. baumannii drug discovery. The present review discusses the bacterial research community's efforts in the field of A. baumannii, focusing on the strategies adapted to identify potent scaffolds and novel targets to bolster and diversify the chemical space available for drug discovery. Firstly, we have discussed existing chemotherapy and various anti-microbial resistance mechanisms in A. baumannii bacterial strains. Next, we elaborate on multidisciplinary approaches and strategies that may be the way forward to combat the current menace caused by the drug-resistant A. baumannii strains. The review highlights the recent advances in drug discovery, including combinational therapy, high-throughput screening, drug repurposing, nanotechnology, and anti-microbial peptides, which are imperative tools to fight bacterial pathogens in the future.

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2.40%
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129
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