The AraC/XylS family of transcriptional regulators is one of the most common families of positive regulators in bacteria. Members of this family are widely distributed in diverse prokaryote genera that are broadly distributed in gram-negative and gram-positive bacteria. Members of the AraC/XylS family belong to an ancient lineage, as deduced from the great evolutionary distance between prokaryotes with XylS/AraC proteins, and from the existence of marked differences in their G+C content.

             This family is characterized by significant aminoacid sequence homology extending over a 100-residue stretch constituting the DNA binding domain.

             All the XylS/AraC proteins fulfil the profile PS01124 of PROSITE. The value obtained after matching with the PROSITE profile PS01124 is always above the 12.52 threshold in proteins that belong to the AraC/XylS family.

             The AraC/XylS proteins have a common three-dimensional structure of the DNA-binding domain. This domain corresponds to the stretch defined in the PROSITE profile. It is composed by two Helix-Turn-Helix (H-T-H) motifs that interact with adjacent major grooves corresponding to the DNA-binding sites.

             Although some proteins of the family are uniquely constituted by the DNA-binding domain, the majority of the proteins of the family have a domain of dimerization and binding to the effector.

             All proteins in the AraC/XylS family are positive transcriptional activators except CelD , which seems to act as a repressor. Several members of the family funtion both as a repressor and as a positive regulator. Their double action can be mediated by the binding to two different promoters (AraC) or alternatively by the binding in a different conformational structure to the same promoter. The binding to effectors mediates the conformational change.

             These transcriptional regulators respond to enviromental signals (oxidative stress, temperature, osmolarity, calcium concentration, pH, effectors). One group of these proteins contains a signal-receptor domain in addition to the DNA-binding domain. In other groups, the signal receptor is another protein that controls the syntesis of the AraC/XylS regulator protein.

             The proteins belonging to the family share three main regulatory funtions: carbon metabolism, stress response and pathogenesis.

             The family proteins involved in carbon metabolism control the degradation of sugars, alcohols, alkylbenzoates, p-hydroxyphenylacetic acid and herbicides. These transcriptional regulators stimulate the transcription from cognate promoters in response to the presence of the effector.

             Several regulatory proteins are involved in pathogenesis, producing virulence factors of microorganisms that infect plants and mammals. The AraC/XylS proteins that participate in the virulence of bacteria colonizing the gastrointestinal tract, the respiratory tract and the urinary system are particularly important. Their study can provide new therapeutic tools for the most common human infections.

             Taking into account the functions that the AraC/XylS family of transcriptional proteins regulate, it is reasonable to consider these proteins as possible targets for designing a broad spectrum of applications in the fields of biotechnology and medicine. Thus, their participation in the regulation of the use of C-sources and in the metabolism of recalcitrant pollutants establishes a relation between this family and the catabolism of biogenic and xenobiotic compounds. The involvement of AraC/XylS proteins in antibiotic resistance and in the pathogenesis of common diseases such as enterocolitis as well as respiratory and urinary infections, emphasizes the importance of these regulators as targets for new drugs. In parallel, their role in abiotic stress responses establishes a link with the ecological adaptation of microbes to changing environmental conditions.