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Isolation of Highly Persistent Mutants of Salmonella enterica Serovar Typhimurium Reveals a New Toxin-Antitoxin Module
- Slattery, Andrew, Victorsen, Alec H., Brown, April, Hillman, Kai, Phillips, Gregory J.
- Journal of bacteriology 2013 v.195 no.4 pp. 647-657
- Escherichia coli K12, Salmonella enterica subsp. enterica serovar Typhimurium, ampicillin, antitoxins, bacteriology, epigenetics, genes, loci, mutants, nonsense mutation, pathogen survival, phenotype, physiological state, proteinases
- 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.