Formation of persister cells is one of the most important survival mechanism of bacterial population. This mechanism allows a small fraction of cells to enter a dormant state and thus save themselves and the whole population from antibiotic stress. Different Toxin Anti-toxin (TA) modules seem to play an important role in the formation of persister cells, HipAB being the first one directly correlated to the this phenotype. Ectopic expression of HipA arrests cell growth and mediates, in an unclear mechanism, the formation of persister cells. This dormant state of the cells was also related to the stringent response. In this response the synthesis of the signal molecule (p)ppGpp during starvation or at the entrance to stationary phase, changes the transcriptional profile of the cells and causes growth arrest, so the cells can overcome stress conditions. Cells lacking the ability to synthesize (p)ppGpp would produce less persisters. The onset of the stringent response, which triggers polyphosphate accumulation, seems to trigger persistent formation, probably by leading to the degradation of antitoxins in the cell by Lon protease. HipB is one of the antitoxins that are degraded by Lon, leading to free HipA in the cell. We propose a novel target of HipA, GltX, which uncovers another piece in the persisters puzzle.
