Increasing antibiotic resistance in Gram-negative bacteria has mandated the development of both novel antibiotics and alternative therapeutic strategies. Evidence of interplay between several gastrointestinal peptides and the gut microbiota led us to investigate potential and broad-spectrum roles for the incretin hormone, human glucose-dependent insulinotropic polypeptide (GIP) against the Enterobacteriaceae bacteria, Escherichia coli and Erwinia amylovora . GIP had a potent disruptive action on drug efflux pumps of the multidrug resistant bacteria E. coli TG1 and E. amylovora 1189 strains. The effect was comparable to bacterial mutants lacking the inner and outer membrane efflux pump factor proteins AcrB and TolC. While GIP was devoid of direct antimicrobial activity, it has a potent membrane depolarizing effect, and at low concentrations, it significantly potentiated the activity of eight antibiotics and bile salt by reducing MICs by 4-8-fold in E. coli TG1 and 4-20-fold in E. amylovora 1189 . GIP can thus be regarded as an antimicrobial adjuvant with potential for augmenting the available antibiotic arsenal.

中文翻译：

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人葡萄糖依赖性促胰岛素多肽 (GIP) 是一种抗菌佐剂，可使多重耐药革兰氏阴性菌重新敏化


革兰氏阴性细菌中抗生素耐药性的增加要求开发新型抗生素和替代治疗策略。几种胃肠道肽和肠道微生物群之间相互作用的证据促使我们研究肠促胰岛素激素、人葡萄糖依赖性促胰岛素多肽（GIP）对抗肠杆菌科细菌、大肠杆菌和解淀粉欧文氏菌的潜在和广谱作用。 GIP 对多重耐药细菌 E. coli TG1 和 E. amylovora 1189 菌株的药物流出泵具有有效的破坏作用。该效果与缺乏内膜和外膜流出泵因子蛋白 AcrB 和 TolC 的细菌突变体相当。虽然 GIP 缺乏直接抗菌活性，但它具有有效的膜去极化作用，并且在低浓度下，它可将大肠杆菌 TG1 和 4- 中的 MIC 降低 4-8 倍，从而显着增强八种抗生素和胆盐的活性。第 1189 章因此，GIP 可以被视为一种抗菌佐剂，具有扩大可用抗生素库的潜力。