At the top, H-NS positively controls motility and represses acid stress

resistance. Genes in cross symbol are directly activated by H-NS; in rectangle: GANT61 cell line directly repressed by H-NS; in circle: indirectly repressed by H-NS. Regulatory proteins are indicated with upper case. Orange filling: flagellum synthesis process; Pink filling: glutamate-dependent acid resistance process; Blue filling: arginine-dependent acid resistance process; Red filling: lysine-dependent acid resistance process; Green filling: genes involved in three different acid resistance processes. Gene names in yellow indicate the direct targets of RcsB-P/GadE complex placed at the centre of this regulatory cascade. A positive effect on transcription is indicated by arrows and a negative regulatory effect is indicated by blunt ended lines. Direct regulation is indicated by solid lines. Indirect regulation is indicated by dashed lines. BIX 1294 concentration Previously published results are included in the scheme: [1–3, 5–7, 10, 16, 32–40]. Among the H-NS-regulated genes, we showed that the acid stress chaperones HdeA and HdeB that solubilized periplasmic protein aggregates at acid pH [26] are

involved in all three pathways check details of acid stress response. However, their impact is low in the arginine- and lysine-dependent pathways (Table 3), while they are essential in the glutamate-dependent pathway [27]. This could be explained by the fact that arginine and lysine amino acids are able to strongly oppose protein aggregation [28]. By contrast, Oxaprozin we found that the expression of the dps gene, directly regulated by H-NS and known to protect cells against multiple stresses [29], is essential to lysine- and arginine-dependent responses to acid stress, while its role

is less important during the glutamate-dependent response (Table 2 and 3). This implies that the induced glutamate-dependent response provides sufficient cell protection, restricting Dps to a marginal role. This is consistent with the observation that glutamate is widely distributed amino acid representing approximately 15–45% in the dietary protein content and plays a key physiological role in gastrointestinal tract [30]. Within this frame of thought, the glutamate decarboxylase system would be the most efficient acid resistance mechanism [31]. This could also explain why three regulators H-NS, HdfR and RcsB are directly involved in the control of both glutamate-dependent acid stress response and the flagellum biosynthesis. Indeed, as flagellum is a high consumer of ATP and leads to proton entrance during its motor functioning, it is necessary to stop this process to limit cytoplasmic acidification in bacteria and to redirect energy to mechanisms of resistance to stress. Furthermore, the flagellar filaments bear strong antigenic properties in contact with host.