title: Energy production genes sucB and ubiF are involved in persister survival and tolerance to multiple antibiotics and stresses in Escherichia coli.
abstract: Persisters are a small population of slowly growing or nongrowing bacteria that are phenotypically resistant to antibiotics, but the mechanisms involved are not well understood. The aim of this study is to determine new mechanisms underlying antibiotic-tolerant persisters. The Escherichia coli deletion mutant library was screened to identify mutants that had a defect in persister survival after exposure to ampicillin for 24 h or 5 days. The identified mutants and the parent strain were subjected to minimum inhibitory concentration (MIC) and minimum bactericidal tests and antibiotic or stress conditions in exposure assays. sucB and ubiF mutants deficient in energy production were identified from the mutant screens to have defective persister survival as demonstrated by higher susceptibility to various antibiotics, including ampicillin, norfloxacin, tetracycline and gentamicin, and different stresses such as oxidative stress, acid pH and weak acid compared with the parent strain. In addition, both sucB and ubiF had a twofold lower MIC than the parent strain. The above sucB and ubiF mutant phenotypes could be complemented by their respective functional genes. Defective energy production through mutations in sucB and ubiF affects persister survival and could serve as new drug targets for persister bacteria.
authors.affiliation: Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Ma
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Sim
authors.forename: Wanliang
authors.initials: W
authors.lastname: Shi
authors.forename: Lijun
authors.initials: L
authors.lastname: Du
authors.forename: Dongming
authors.initials: D
authors.lastname: Xing
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000143:Acids / Q000494:pharmacology; D000667:Ampicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D005816:Genetic Complementation Test; D007655:Ketoglutarate Dehydrogenase Complex / Q000235:genetics / Q000502:physiology*; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000502:physiology*; D018384:Oxidative Stress; D013312:Stress, Physiological
chemical_list: D000143:Acids; D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins; D000667:Ampicillin; D006899:Mixed Function Oxygenases; C410160:UbiF protein, E coli; D007655:Ketoglutarate Dehydrogenase Complex; C553252:sucB protein, E coli