Department of Chemistry, Vanderbilt University, Nashville, Tennessee, USA.
Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA.
mBio. 2020 Mar 17;11(2):e00076-20. doi: 10.1128/mBio.00076-20.
Adjuvants can be used to potentiate the function of antibiotics whose efficacy has been reduced by acquired or intrinsic resistance. In the present study, we discovered that human milk oligosaccharides (HMOs) sensitize strains of group B (GBS) to trimethoprim (TMP), an antibiotic to which GBS is intrinsically resistant. Reductions in the MIC of TMP reached as high as 512-fold across a diverse panel of isolates. To better understand HMOs' mechanism of action, we characterized the metabolic response of GBS to HMO treatment using ultrahigh-performance liquid chromatography-high-resolution tandem mass spectrometry (UPLC-HRMS/MS) analysis. These data showed that when challenged by HMOs, GBS undergoes significant perturbations in metabolic pathways related to the biosynthesis and incorporation of macromolecules involved in membrane construction. This study represents reports the metabolic characterization of a cell that is perturbed by HMOs. Group B is an important human pathogen that causes serious infections during pregnancy which can lead to chorioamnionitis, funisitis, premature rupture of gestational membranes, preterm birth, neonatal sepsis, and death. GBS is evolving antimicrobial resistance mechanisms, and the work presented in this paper provides evidence that prebiotics such as human milk oligosaccharides can act as adjuvants to restore the utility of antibiotics.
佐剂可用于增强抗生素的功能，这些抗生素的疗效因获得性或固有耐药性而降低。在本研究中，我们发现人乳寡糖（HMOs）可使 B 群（GBS）对 trimethoprim（TMP）敏感，TMP 是 GBS 固有耐药的抗生素。在不同的分离株中，TMP 的 MIC 降低高达 512 倍。为了更好地了解 HMOs 的作用机制，我们使用超高效液相色谱-高分辨率串联质谱（UPLC-HRMS/MS）分析来表征 GBS 对 HMO 处理的代谢反应。这些数据表明，当受到 HMOs 的挑战时，GBS 在与生物合成和整合涉及膜构建的大分子有关的代谢途径中经历显著的扰动。本研究报告了一种受 HMOs 干扰的细胞的代谢特征。B 群是一种重要的人类病原体，在怀孕期间会引起严重感染，导致绒毛膜羊膜炎、脐带炎、胎膜早破、早产、新生儿败血症和死亡。GBS 正在进化抗微生物耐药机制，本文介绍的工作提供了证据表明，人乳寡糖等益生元可以作为佐剂恢复抗生素的效用。
