title: Isolation of highly persistent mutants of Salmonella enterica serovar typhimurium reveals a new toxin-antitoxin module.
abstract: Bacterial persistence is characterized by the ability of a subpopulation within bacterial cultures to survive exposure to antibiotics and other lethal treatments. The surviving persisters are not the result of genetic changes but represent epigenetic variants that are in a physiological state where growth is inhibited. Since characterization of persisters has been performed mainly in Escherichia coli K-12, we sought to identify mechanisms of persistence in the pathogen Salmonella enterica serovar Typhimurium. Isolation of new highly persistent mutants revealed that the shpAB locus (Salmonella high persistence) imparted a 3- to 4-order-of-magnitude increase in survival after ampicillin exposure throughout its growth phase and protected the population against exposure to multiple antibiotics. Genetic characterization revealed that shpAB is a newly discovered toxin-antitoxin (TA) module. The high-persistence phenotype was attributed to a nonsense mutation in the 3' end of the shpB gene encoding an antitoxin protein. Characteristic of other TA modules, shpAB is autoregulated, and high persistence depends on the Lon protease.
authors.affiliation: Department of Veterinary Microbiology, Iowa State University, Ames, IA, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Slattery
authors.forename: Alec H
authors.initials: AH
authors.lastname: Victorsen
authors.forename: April
authors.initials: A
authors.lastname: Brown
authors.forename: Kai
authors.initials: K
authors.lastname: Hillman
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Phillips
mesh_terms: D000595:Amino Acid Sequence; D000667:Ampicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000992:Antitoxins / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism*; D002874:Chromosome Mapping; D024881:Drug Resistance, Bacterial / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D005818:Genetic Engineering; D016680:Genome, Bacterial; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D010957:Plasmids; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D000900:Anti-Bacterial Agents; D000992:Antitoxins; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D000667:Ampicillin