The Sulfide-Responsive SqrR/BigR Homologous Regulator YgaV of Escherichia coli Controls Expression of Anaerobic Respiratory Genes and Antibiotic Tolerance

Compositions and activities of bacterial flora in the gastrointestinal tract significantly influence the metabolism, health, and disease of host humans and animals. These enteric bacteria can switch between aerobic and anaerobic growth if oxygen tension becomes limited. Interestingly, the switching mechanism is important for preventing reactive oxygen species (ROS) production and antibiotic tolerance. Studies have also shown that intracellular and extracellular sulfide molecules are involved in this switching control, although the mechanism is not fully clarified. Here, we found that YgaV, a sulfide-responsive transcription factor SqrR/BigR homolog, responded to sulfide compounds in vivo and in vitro to control anaerobic respiratory gene expression. YgaV also responded to H₂O₂ scavenging in the enteric bacterium Escherichia coli. Although the wild-type (WT) showed increased antibiotic tolerance under H₂S-atmospheric conditions, the ygaV mutant did not show such a phenotype. Additionally, antibiotic sensitivity was higher in the mutant than in the WT of both types in the presence and absence of exogenous H₂S. These results, therefore, indicated that YgaV-dependent transcriptional regulation was responsible for maintaining redox homeostasis, ROS scavenging, and antibiotic tolerance.