biostudies-literatureChen XWResearch Council of NorwayNational Natural Science Foundation of ChinaThe Youth Talent Support Program of Guangdong Province2180938https://www.ebi.ac.uk/biostudies/studies/S-EPMC9980678biostudies-literatureUnknown14(1)<i>Streptococcus agalactiae</i> (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 <i>Staphylococcus aureus</i> (MRSA) and NDM-1 expressing <i>Escherichia coli</i>. 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.VirulenceFructose promotes ampicillin killing of antibiotic-resistant <i>Streptococcus agalactiae</i>.PMC99806782017GC01061732069232061133007Munang'andu HMLiu YLPeng BChen XWWu JHfalseFructose promotes ampicillin killing of antibiotic-resistant <i>Streptococcus agalactiae</i>.<i>Streptococcus agalactiae</i> (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 <i>Staphylococcus aureus</i> (MRSA) and NDM-1 expressing <i>Escherichia coli</i>. 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.2023-01-01T00:00:00Z2023 Dec2024-11-09T06:04:12.766Z2024-11-09T06:04:12.766ZS-EPMC99806783680352810.1080/21505594.2023.2180938