title: Arrested protein synthesis increases persister-like cell formation.
abstract: Biofilms are associated with a wide variety of bacterial infections and pose a serious problem in clinical medicine due to their inherent resilience to antibiotic treatment. Within biofilms, persister cells comprise a small bacterial subpopulation that exhibits multidrug tolerance to antibiotics without undergoing genetic change. The low frequency of persister cell formation makes it difficult to isolate and study persisters, and bacterial persistence is often attributed to a quiescent metabolic state induced by toxins that are regulated through toxin-antitoxin systems. Here we mimic toxins via chemical pretreatments to induce high levels of persistence (10 to 100%) from an initial population of 0.01%. Pretreatment of Escherichia coli with (i) rifampin, which halts transcription, (ii) tetracycline, which halts translation, and (iii) carbonyl cyanide m-chlorophenylhydrazone, which halts ATP synthesis, all increased persistence dramatically. Using these compounds, we demonstrate that bacterial persistence results from halted protein synthesis and from environmental cues.
authors.affiliation: Department of Chemical Engineering, Pennsylvania State University, University Park, PA, USA.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Kwan
authors.forename: John A
authors.initials: JA
authors.lastname: Valenta
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Benedik
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Wood
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects*; D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D061209:Proton Ionophores / Q000494:pharmacology; D012293:Rifampin / Q000494:pharmacology; D013752:Tetracycline / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D029968:Escherichia coli Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D011500:Protein Synthesis Inhibitors; D061209:Proton Ionophores; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D000255:Adenosine Triphosphate; D013752:Tetracycline; D012293:Rifampin