Fructose promotes ampicillin killing of antibiotic-resistant Streptococcus agalactiae
Xuan-Wei Chen,
Jia-Han Wu,
Ying-Li Liu,
Hetron Mweemba Munang’andu,
Bo Peng
Affiliations
Xuan-Wei Chen
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
Jia-Han Wu
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
Ying-Li Liu
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
Hetron Mweemba Munang’andu
Faculty of Biosciences and Aquaculture, Nord University, Bodo, Norway
Bo Peng
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
ABSTRACTStreptococcus agalactiae (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 Staphylococcus aureus (MRSA) and NDM-1 expressing Escherichia coli. 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.
