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反对使用抗生素而支持抗毒力疗法的理由。

The Case against Antibiotics and for Anti-Virulence Therapeutics.

作者信息

Hotinger Julia A, Morris Seth T, May Aaron E

机构信息

Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23219, USA.

出版信息

Microorganisms. 2021 Sep 28;9(10):2049. doi: 10.3390/microorganisms9102049.

Abstract

Although antibiotics have been indispensable in the advancement of modern medicine, there are downsides to their use. Growing resistance to broad-spectrum antibiotics is leading to an epidemic of infections untreatable by first-line therapies. Resistance is exacerbated by antibiotics used as growth factors in livestock, over-prescribing by doctors, and poor treatment adherence by patients. This generates populations of resistant bacteria that can then spread resistance genes horizontally to other bacterial species, including commensals. Furthermore, even when antibiotics are used appropriately, they harm commensal bacteria leading to increased secondary infection risk. Effective antibiotic treatment can induce bacterial survival tactics, such as toxin release and increasing resistance gene transfer. These problems highlight the need for new approaches to treating bacterial infection. Current solutions include combination therapies, narrow-spectrum therapeutics, and antibiotic stewardship programs. These mediate the issues but do not address their root cause. One emerging solution to these problems is anti-virulence treatment: preventing bacterial pathogenesis instead of using bactericidal agents. In this review, we discuss select examples of potential anti-virulence targets and strategies that could be developed into bacterial infection treatments: the bacterial type III secretion system, quorum sensing, and liposomes.

摘要

尽管抗生素在现代医学的发展中不可或缺,但它们的使用也存在弊端。对广谱抗生素的耐药性不断增加,导致一线治疗无法治愈的感染流行。家畜中用作生长因子的抗生素、医生的过度开方以及患者治疗依从性差,都加剧了耐药性。这产生了耐药细菌群体,然后这些细菌可以将耐药基因水平转移到其他细菌物种,包括共生菌。此外,即使抗生素使用得当,它们也会损害共生细菌,导致二次感染风险增加。有效的抗生素治疗可以诱导细菌的生存策略,如毒素释放和增加耐药基因转移。这些问题凸显了治疗细菌感染新方法的必要性。目前的解决方案包括联合疗法、窄谱疗法和抗生素管理计划。这些措施缓解了问题,但没有解决其根本原因。针对这些问题的一个新兴解决方案是抗毒力治疗:预防细菌发病机制而不是使用杀菌剂。在这篇综述中,我们讨论了一些潜在的抗毒力靶点和策略的选定例子,这些靶点和策略可以发展成为细菌感染治疗方法:细菌III型分泌系统、群体感应和脂质体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2427/8537500/9ce3e80a20d7/microorganisms-09-02049-g001.jpg

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