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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.