Protein Structure-Function and Research Unit, School of Molecular and Cell Biology, Faculty of Science, University of the Witwatersrand, Braamfontein, Johannesburg, 2050, South Africa; Department of Medical Biochemistry, Alex Ekwueme Federal University Ndufu-Alike, Ebonyi State, Nigeria.
Protein Structure-Function and Research Unit, School of Molecular and Cell Biology, Faculty of Science, University of the Witwatersrand, Braamfontein, Johannesburg, 2050, South Africa.
Microb Pathog. 2023 Feb;175:105963. doi: 10.1016/j.micpath.2022.105963. Epub 2022 Dec 27.
Globally, the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are the major cause of nosocomial infections. These pathogens are multidrug resistant, and their negative impacts have brought serious health challenges and economic burden on many countries worldwide. Thus, this narrative review exploits different emerging alternative therapeutic strategies including combination antibiotics, antimicrobial peptides ((AMPs), bacteriophage and photodynamic therapies used in the treatment of the ESKAPE pathogens, their merits, limitations, and future prospects. Our findings indicate that ESKAPE pathogens exhibit resistance to drug using different mechanisms including drug inactivation by irreversible enzyme cleavage, drug-binding site alteration, diminution in permeability of drug or drug efflux increment to reduce accumulation of drug as well as biofilms production. However, the scientific community has shown significant interest in using these novel strategies with numerous benefits although they have some limitations including but not limited to instability and toxicity of the therapeutic agents, or the host developing immune response against the therapeutic agents. Thus, comprehension of resistance mechanisms of these pathogens is necessary to further develop or modify these approaches in order to overcome these health challenges including the barriers of bacterial resistance.
在全球范围内,ESKAPE 病原体(屎肠球菌、金黄色葡萄球菌、肺炎克雷伯菌、鲍曼不动杆菌、铜绿假单胞菌和肠杆菌属)是医院感染的主要原因。这些病原体具有多重耐药性,它们的负面影响给世界上许多国家带来了严重的健康挑战和经济负担。因此,本叙述性评论探讨了不同新兴的替代治疗策略,包括联合抗生素、抗菌肽 (AMPs)、噬菌体和光动力疗法在治疗 ESKAPE 病原体中的应用,以及它们的优点、局限性和未来前景。我们的研究结果表明,ESKAPE 病原体表现出对药物的耐药性,其机制包括不可逆酶裂解使药物失活、药物结合部位改变、药物通透性降低或药物外排增加以减少药物积累以及生物膜的产生。然而,科学界对这些新策略表现出了极大的兴趣,尽管它们存在一些局限性,包括但不限于治疗剂的不稳定性和毒性,或者宿主对治疗剂产生免疫反应,但它们具有许多益处。因此,了解这些病原体的耐药机制对于进一步开发或改进这些方法以克服这些健康挑战包括细菌耐药性的障碍是必要的。