Glucose-Induced Cyclic Lipopeptides Resistance in Bacteria via ATP Maintenance through Enhanced Glycolysis

• Published in: iScience Vol. 21; pp. 135 - 144
• Main Authors: Yu, Wen-Bang, Pan, Qian, Ye, Bang-Ce
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 22.11.2019; Elsevier
• Subjects: Microbial Metabolism; Microbiology; Molecular Mechanism of Behavior; Multi-Drug Resistant Organisms; Molecular Mechanism of Behavior; Microbiology; Microbial Metabolism; Multi-Drug Resistant Organisms
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2019.10.009

Cyclic lipopeptide (CLP) antibiotics have a mechanism that causes membrane malfunction. Thus mechanisms of bacterial resistance to CLPs are thought to modify cell surfaces. However, we found that bacterial resistance to CLPs was strongly related to energy metabolism. Using polymyxin B (PB) as a model of CLPs, we showed that PB causes malfunction of respiration and serious depletion of ATP, contributing to PB-induced cell death and carbon starvation. Glucose addition could maintain the intracellular ATP level and reverse the carbon starvation response resulting from PB treatment. Another study revealed that glycolysis was stimulated by the presence of PB and glucose. The mechanism underlying glucose-enabled CLPs' resistance suggests that glucose could maintain the ATP level in PB-treated bacteria by enhancing glycolysis. Similar results were observed in Staphylococcus aureus, where daptomycin resistance was enhanced by glucose. These findings provide insight into the mode of action of CLPs and resistance to these antibiotics. [Display omitted] •Glucose induces the drug resistance to CLPs•CLPs significantly inhibit energy metabolism and result in ATP depletion•Glucose maintains the intracellular ATP level in CLP-treated bacteria Multi-Drug Resistant Organisms; Molecular Mechanism of Behavior; Microbiology; Microbial Metabolism