关键词: Antibiotic susceptibility Antimicrobial resistance Gram-negative bacteria Metabolic modulation Metabolism Antibiotic susceptibility Antimicrobial resistance Gram-negative bacteria Metabolic modulation Metabolism

Mesh : Anti-Bacterial Agents / metabolism pharmacology therapeutic use Anti-Infective Agents / metabolism Bacteria / metabolism Gram-Negative Bacteria Metabolomics Anti-Bacterial Agents / metabolism pharmacology therapeutic use Anti-Infective Agents / metabolism Bacteria / metabolism Gram-Negative Bacteria Metabolomics

来  源:   DOI:10.1007/s11306-022-01903-w

Abstract:
The rise of antimicrobial resistance at an alarming rate is outpacing the development of new antibiotics. The worrisome trends of multidrug-resistant Gram-negative bacteria have enormously diminished existing antibiotic activity. Antibiotic treatments may inhibit bacterial growth or lead to induce bacterial cell death through disruption of bacterial metabolism directly or indirectly. In light of this, it is imperative to have a thorough understanding of the relationship of bacterial metabolism with antimicrobial activity and leverage the underlying principle towards development of novel and effective antimicrobial therapies.
Herein, we explore studies on metabolic analyses of Gram-negative pathogens upon antibiotic treatment. Metabolomic studies revealed that antibiotic therapy caused changes of metabolites abundance and perturbed the bacterial metabolism. Following this line of thought, addition of exogenous metabolite has been employed in in vitro, in vivo and in silico studies to activate the bacterial metabolism and thus potentiate the antibiotic activity.
Exogenous metabolites were discovered to cause metabolic modulation through activation of central carbon metabolism and cellular respiration, stimulation of proton motive force, increase of membrane potential, improvement of host immune protection, alteration of gut microbiome, and eventually facilitating antibiotic killing. The use of metabolites as antimicrobial adjuvants may be a promising approach in the fight against multidrug-resistant pathogens.
摘要:
抗菌素耐药性以惊人的速度上升,超过了新抗生素的开发。多药耐药革兰氏阴性菌的令人担忧的趋势极大地削弱了现有的抗生素活性。抗生素治疗可以通过直接或间接破坏细菌代谢来抑制细菌生长或导致细菌细胞死亡。鉴于此,我们必须彻底了解细菌代谢与抗菌活性之间的关系,并利用基本原则开发新型有效的抗菌疗法。
这里,我们探索抗生素治疗后革兰氏阴性病原体代谢分析的研究。代谢组学研究表明,抗生素治疗会引起代谢产物丰度的变化并干扰细菌代谢。遵循这个思路,添加外源代谢物已在体外使用,体内和计算机研究,以激活细菌代谢,从而增强抗生素活性。
发现外源代谢物通过激活中心碳代谢和细胞呼吸引起代谢调节,质子动力的刺激,膜电位的增加,改善宿主免疫保护,肠道微生物组的改变,并最终促进抗生素的杀灭。使用代谢物作为抗微生物佐剂可能是对抗多药耐药病原体的有希望的方法。
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