摘要

    伯克霍尔德氏菌病原体中高度保守的PenI型A类β-内酰胺酶可以进化为广谱β-内酰胺酶（ESBL），对第三代头孢菌素表现出水解活性，而对原始的青霉素底物却失去活性。 我们描述了ArgS精氨酸-tRNA合成酶中的三个单氨基酸取代突变，这些突变赋予ESBL生产Burkholderia thailandensis额外的抗生素耐受性保护。 在开发针对伯克霍尔德氏菌的治疗措施时，可以利用该途径来逃避抗生素耐受性诱导，靶向其必需的氨酰基-tRNA合成酶。

    Highly conserved PenI-type class A β-lactamase in pathogenic members of Burkholderia species can evolve to extended-spectrum β-lactamase (ESBL), which exhibits hydrolytic activity toward third-generation cephalosporins, while losing its activity toward the original penicillin substrates. We describe three single-amino-acid-substitution mutations in the ArgS arginine-tRNA synthetase that confer extra antibiotic tolerance protection to ESBL-producing Burkholderia thailandensis. This pathway can be exploited to evade antibiotic tolerance induction in developing therapeutic measures against Burkholderia species, targeting their essential aminoacyl-tRNA synthetases.

    https://aac.asm.org/content/64/6/e02252-19.abstract