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-orderof-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.

LITERATURE REVIEW Bacterial Persistence Characterization of persistent cells Growth phase effect on persistence Persistence as an evolutionary adaptation Possible explanations of persistence Additional explanations of persistence Research to understand persistence High persistence mutants of E. coli hip A 7 phenotype Growth phase effect on E. coli hipA 7 mutant persistence The hip operon hip operon deletions HipA and HipB proteins hipA7 production of persistent cells Cellular action of hipAB and the mutant hipA 7 hipQ Why study persistence? Salmonella ISOLATION AND CHARACTERIZATION OF HIGH PERSISTENCE MUTANTS OF SALMONELLA ENTER/CA SEROTYPE TYPHIMURIUM Abstract Introduction Materials and Methods Results Discussion Table and figure titles Tables and figures GENERAL CONCLUSIONS REFERENCES 1 2 2