State Key Laboratory of Biocontrol, Guangdong Key Laboratory of Pharmaceutical Functional Genes, School of Life Sciences, Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Sun Yat-sen University, Higher Education Mega Center, Guangzhou, China.
Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China.
Virulence. 2023 Dec;14(1):2180938. doi: 10.1080/21505594.2023.2180938.
(GBS) is an important pathogenic bacteria that infected both aquatic animals and human beings, causing huge economic loss. The increasing cases of antibiotic-resistant GBS impose challenges to treat such infection by antibiotics. Thus, it is highly demanded for the approach to tackle antibiotic resistance in GBS. In this study, we adopt a metabolomic approach to identify the metabolic signature of ampicillin-resistant GBS (AR-GBS) that ampicillin is the routine choice to treat infection by GBS. We find glycolysis is significantly repressed in AR-GBS, and fructose is the crucial biomarker. Exogenous fructose not only reverses ampicillin resistance in AR-GBS but also in clinic isolates including methicillin-resistant (MRSA) and NDM-1 expressing . The synergistic effect is confirmed in a zebrafish infection model. Furthermore, we demonstrate that the potentiation by fructose is dependent on glycolysis that enhances ampicillin uptake and the expression of penicillin-binding proteins, the ampicillin target. Our study demonstrates a novel approach to combat antibiotic resistance in GBS.
（GBS）是一种重要的致病性细菌，可感染水生动物和人类，造成巨大的经济损失。越来越多的耐抗生素 GBS 病例对使用抗生素治疗此类感染提出了挑战。因此，需要采取一种方法来解决 GBS 的抗生素耐药性问题。在这项研究中，我们采用代谢组学方法来鉴定氨苄青霉素耐药性 GBS（AR-GBS）的代谢特征，氨苄青霉素是常规选择来治疗 GBS 感染。我们发现 AR-GBS 中的糖酵解受到显著抑制，而果糖是关键的生物标志物。外源性果糖不仅可以逆转 AR-GBS 中的氨苄青霉素耐药性，还可以逆转包括耐甲氧西林金黄色葡萄球菌（MRSA）和表达 NDM-1 的临床分离株的耐药性。在斑马鱼感染模型中证实了协同作用。此外，我们证明果糖的增效作用依赖于糖酵解，增强了氨苄青霉素的摄取和青霉素结合蛋白的表达，即氨苄青霉素的靶标。我们的研究展示了一种对抗 GBS 抗生素耐药性的新方法。
