Metabolic aspects of bacterial persisters.
Persister cells form a multi-drug tolerant subpopulation within an isogenic culture of bacteria that are genetically susceptible to antibiotics. Studies with different Gram negative and Gram positive bacteria have identified a large number of genes associated with the persister state. In contrast, the revelation of persister metabolism has only been addressed recently. We here summarize metabolic aspects of persisters, which includes an overview about the bifunctional role of selected carbohydrates as both triggers for the exit from the drug tolerant state and metabolites which persisters feed on. Also alarmones as indicators for starvation have been shown to influence persister levels via different signaling cascades involving the activation of toxin-antitoxin systems and other regulatory factors. Finally, recent data obtained by (13)C-isotopolog profiling demonstrated an active amino acid anabolism in Staphylococcus aureus cultures challenged with high drug concentrations. Understanding the metabolism of persister cells poses challenges but also paves the way for the development of anti-persister compounds.
Department of Microbial Genetics, Faculty of Science, Interfaculty Institute of Microbiology and Infection Medicine Tübingen (IMIT), University of Tübingen Tübingen, Germany.
Marcel
M
Prax
Department of Microbial Genetics, Faculty of Science, Interfaculty Institute of Microbiology and Infection Medicine Tübingen (IMIT), University of Tübingen Tübingen, Germany.
Ralph
R
Bertram
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D018407:Bacterial Physiological Phenomena / Q000187:drug effects / Q000235:genetics; D050260:Carbohydrate Metabolism; D024881:Drug Resistance, Bacterial / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects
D000900:Anti-Bacterial Agents
Staphylococcus aureus; biofilm; metabolism; persisters; ppGpp; toxin-antitoxin system