## 3 Protective and Repair Mechanisms against Acid Stress
Similarly, the chaperonin DnaK has been associated with acid tolerance in _L. monocytogenes_. A mutant strain lacking a functional _dnaK_ gene exhibits reduced survival at low pH and high temperatures [70]. Dps is a DNA-binding protein expressed predominantly in starved _E. coli_ cells and is highly conserved and broadly distributed throughout the bacterial domain of life [71]. In _E. coli_, Dps is one of the most abundant proteins during stationary growth and it protects cells against an array of stresses, including oxidative stress, starvation, heat shock and extreme pHs [72; 73; 74]. Dps expression is independently regulated by OxyR in exponentially growing cells and by the alternative sigma factor, sigma S (RpoS or \(\sigma^{8}\)) and the histone-like integration host factor (IHF) during stationary phase [75]. Dps assembles into a dodecameric cage-like structure [76] and its protective effects are a consequence of three distinct biochemical mechanisms: Dps can bind and shield DNA from chemical damage, sequestrate Fe\({}^{2+}\) ions in its core and oxidize iron by means of its 'ferritin-like' ferrooxidase activity [77; 78; 79; 74]. Under acid stress conditions, _dps_' mutants show 100-fold-greater sensitivity after 30 min at pH 2 [73] and DNA damage resulting from acid stress is greater in _dps_ and _recA_ mutants, highlighting also the importance of DNA repair in acid tolerance mechanisms [74]. In _L. monocytogenes_, the Dps homologue, Fri, is a major cold shock protein [80] that contributes to virulence and plays a role against multiple stresses [81; 82; 83; 84] and whose expression is induced by low iron growth conditions [85]. Growth rate of a _fri_' mutant strain is slightly reduced under hyperosmotic stress but is severely affected under acidic conditions (pH 5, HCI) [84]. These observations are similar to the results obtained in _E. coli_, suggesting an analogous role for both ferritin-like proteins in acid stress resistance in these bacteria. Bacteria are able to respond to DNA-damaging agents by activating the SOS response, an inducible system that is involved in DNA repair. Two proteins play relevant regulatory roles in the SOS response: LexA, a repressor of the SOS regulon and RecA, a multifunctional protein involved in DNA recombination and repair that mediates auto-cleavage of LexA and induction of the SOS regulon [86; 87]. In _E. coli_, acid stress produces DNA damage and _recA_ mutants have a highly acid-sensitive phenotype [74]. The intracellular signal for the activation of this pathway includes the generation of single stranded DNA (ssDNA). However, not all the mechanisms that lead to the formation of ssDNA, and thus to SOS response induction, are well understood. Under acidic conditions, the mechanism resulting in the expression of SOS genes in _E. coli_ might be explained by an alteration of the structure of LexA that leads to the formation of aggregates, degradation and de-repression of the SOS regulon genes [88]. In _L. monocytogenes_, a _recA_' mutant was also more sensitive to acid stress than the wild type strain [89], supporting the hypothesis that the SOS response plays an important role in the resistance of _L. monocytogenes_ to acidic conditions.