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毒力与抗生素抗性的复杂关系

发布者:抗性基因网 时间:2018-04-28 浏览量:845


摘要

由过度使用抗生素引起的抗生素抗性可能来自多种机制,特别是毒力和抗生素抗性基因的水平基因转移,这通常由生物膜形成促进。在导致基因型改变的生物膜中看到的表型变化的重要性不能被夸大。无论生物膜是单一微生物还是多种微生物,受外部环境保护的生物膜内的细菌通过信号转导途径(例如,群体感应或双组分系统)进行通信,导致基因表达的全球变化,增强毒力,并加速获得抗生素耐药性。因此,我们必须检查毒力和抗性的遗传变化,不仅在生物膜的情况下,而且还作为不可分割的相关病理学。从观察上看,显然增加的毒力和抗生素抗性的出现常常几乎同时出现;然而,它们的遗传关系相对被忽略。虽然多物种群体中遗传调控的复杂性可能会掩盖致病关系,但发现生物膜细菌中毒力和抗性之间的关键遗传相互作用对于确定新的药物靶标至关重要,最终提供药物发现和开发途径以改善慢性和反复感染。


Antibiotic resistance, prompted by the overuse of antimicrobial agents, may arise from a variety of mechanisms, particularly horizontal gene transfer of virulence and antibiotic resistance genes, which is often facilitated by biofilm formation. The importance of phenotypic changes seen in a biofilm, which lead to genotypic alterations, cannot be overstated. Irrespective of if the biofilm is single microbe or polymicrobial, bacteria, protected within a biofilm from the external environment, communicate through signal transduction pathways (e.g., quorum sensing or two-component systems), leading to global changes in gene expression, enhancing virulence, and expediting the acquisition of antibiotic resistance. Thus, one must examine a genetic change in virulence and resistance not only in the context of the biofilm but also as inextricably linked pathologies. Observationally, it is clear that increased virulence and the advent of antibiotic resistance often arise almost simultaneously; however, their genetic connection has been relatively ignored. Although the complexities of genetic regulation in a multispecies community may obscure a causative relationship, uncovering key genetic interactions between virulence and resistance in biofilm bacteria is essential to identifying new druggable targets, ultimately providing a drug discovery and development pathway to improve treatment options for chronic and recurring infection.

http://www.mdpi.com/2073-4425/8/1/39/htm