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细菌素、强效抗菌肽与对抗多重耐药菌:耐药是否徒劳?

Bacteriocins, Potent Antimicrobial Peptides and the Fight against Multi Drug Resistant Species: Resistance Is Futile?

作者信息

Meade Elaine, Slattery Mark Anthony, Garvey Mary

机构信息

Department of Life Science, Sligo Institute of Technology, F91 YW50 Sligo, Ireland.

Mark Anthony Slattery MVB, Veterinary Practice, Manorhamilton, F91 DP62 Leitrim, Ireland.

出版信息

Antibiotics (Basel). 2020 Jan 16;9(1):32. doi: 10.3390/antibiotics9010032.

Abstract

Despite highly specialized international interventions and policies in place today, the rapid emergence and dissemination of resistant bacterial species continue to occur globally, threatening the longevity of antibiotics in the medical sector. In particular, problematic nosocomial infections caused by multidrug resistant Gram-negative pathogens present as a major burden to both patients and healthcare systems, with annual mortality rates incrementally rising. Bacteriocins, peptidic toxins produced by bacteria, offer promising potential as substitutes or conjugates to current therapeutic compounds. These non-toxic peptides exhibit significant potency against certain bacteria (including multidrug-resistant species), while producer strains remain insusceptible to the bactericidal peptides. The selectivity and safety profile of bacteriocins have been highlighted as superior advantages over traditional antibiotics; however, many aspects regarding their efficacy are still unknown. Although active at low concentrations, bacteriocins typically have low in vivo stability, being susceptible to degradation by proteolytic enzymes. Another major drawback lies in the feasibility of large-scale production, with these key features collectively limiting their current clinical application. Though such limitations require extensive research, the concept of expanding bacteriocins from food preservation to human health opens many fascinating doors, including novel drug delivery systems and anticancer treatment applications.

摘要

尽管当今有高度专业化的国际干预措施和政策,但耐药细菌种类在全球范围内仍在迅速出现和传播,威胁着医疗领域抗生素的使用寿命。特别是,由多重耐药革兰氏阴性病原体引起的医院感染问题给患者和医疗系统都带来了重大负担,年死亡率不断上升。细菌素是细菌产生的肽类毒素,作为当前治疗化合物的替代品或共轭物具有广阔的潜力。这些无毒肽对某些细菌(包括多重耐药菌)具有显著的效力,而产生菌对这些杀菌肽仍不敏感。细菌素的选择性和安全性已被视为优于传统抗生素的显著优势;然而,关于其疗效的许多方面仍不清楚。尽管细菌素在低浓度下具有活性,但它们通常在体内稳定性较低,容易被蛋白酶降解。另一个主要缺点在于大规模生产的可行性,这些关键特性共同限制了它们目前的临床应用。尽管这些限制需要广泛的研究,但将细菌素从食品保鲜扩展到人类健康的概念打开了许多迷人的大门,包括新型药物递送系统和抗癌治疗应用。

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