Penetration through Outer Membrane and Efflux Potential in Pseudomonas aeruginosa of Bulgecin A as an Adjuvant to β-Lactam Antibiotics.

Penetration through Outer Membrane and Efflux Potential in Pseudomonas aeruginosa of Bulgecin A as an Adjuvant to β-Lactam Antibiotics.
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DOI:
10.3390/antibiotics12020358
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发表时间:
2023-02-09
期刊:
影响因子:
4.8
通讯作者:
Mobashery, Shahriar
Mobashery, Shahriar
中科院分区:
医学3区
文献类型:
--
作者:
Kim, Choon;Tomoshige, Shusuke;Lee, Mijoon;Zgurskaya, Helen I.;Mobashery, Shahriar

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革兰氏阴性菌感染的治疗仍然是一个艰巨的临床挑战。鉴于缺乏发现新的抗生素,正在探索的一种策略是使用佐剂来增强现有抗生素的抗菌活性。一种这样的佐剂是Bulgecin A,它允许降低β-内酰胺类抗生素的最低抑菌浓度。我们已经证明,灯盏花素A在其作用模式中抑制三种假单胞裂解糖基酶,但增强活性需要较高的浓度。在这里,我们的文件表明,灯盏花素A不是假单胞外排泵的底物,其功能可能是需要高浓度的罪魁祸首。我们提出的证据表明,渗透到周质的屏障是需要高浓度的Bulgecin A来增强β-内酰胺类抗生素的根源。
The treatment of infections by Gram-negative bacteria remains a difficult clinical challenge. In the light of the dearth of discovery of novel antibiotics, one strategy that is being explored is the use of adjuvants to enhance antibacterial activities of existing antibiotics. One such adjuvant is bulgecin A, which allows for the lowering of minimal-inhibitory concentrations for β-lactam antibiotics. We have shown that bulgecin A inhibits three of the pseudomonal lytic transglycosylases in its mode of action, yet high concentrations are needed for potentiation activity. Herein, we document that bulgecin A is not a substrate for pseudomonal efflux pumps, whose functions could have been a culprit in the need for high concentrations. We present evidence that the penetration barrier into the periplasm is at the root of the need for high concentrations of bulgecin A in its potentiation of β-lactam antibiotics.
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