['Bacterial genomes are compacted by association with histone-like proteins to form a complex known as bacterial chromatin. The histone-like protein HU is capable of binding and bending the DNA molecule, a function related to compaction, protection, and regulation of gene expression. In Helicobacter pylori, HU is the only histone-like protein described so far. Proteomic analysis from our laboratory showed that this protein is overexpressed under acidic stress.', 'We used a purified recombinant wild-type protein and two mutant proteins with the amino acid substitutions K3A/S27D and K62R/V63N/P64A to characterize the function of the N-terminal domain and the flexible arm of HU.', 'In vitro assays for DNA protection, bending, and compaction were performed. We also designed a H.\xa0pylori hup::cat mutant strain to study the role of HU in the acid stress response. HUwt protein binds DNA and promotes its bending and compaction. Compared with the wild-type protein, both mutant proteins have less affinity for DNA and an impaired bending and compaction ability. By using qRT-PCR, we confirmed overexpression of two genes related to acid stress response (ureA and speA). Such overexpression was abolished in the hup::cat strain, which shows an acid-sensitive phenotype.'] Does the DNA-binding protein HU have a regulatory role in the acid stress response mechanism in Helicobacter pylori?