Redox-Regulated Adaptation of Streptococcus oligofermentans to Hydrogen Peroxide Stress

The catalase-negative streptococci produce as well as tolerate high levels of H 2 O 2 . This work reports the molecular mechanisms of low-H 2 O 2 -concentration-induced adaptation to higher H 2 O 2 stress in a Streptococcus species, in which the peroxide-responsive repressor PerR and its redox regulons play the major role. Distinct from the Bacillus subtilis PerR, which is inactivated by H 2 O 2 through histidine oxidation by the Fe 2+ -triggered Fenton reaction, the streptococcal PerR is inactivated by H 2 O 2 oxidation of the structural Zn 2+ binding cysteine residues and thus derepresses the expression of genes defending against oxidative stress. The reversible cysteine oxidation could provide flexibility for PerR regulation in streptococci, and the mechanism might be widely used by lactic acid bacteria, including pathogenic streptococci, containing high levels of cellular manganese, in coping with oxidative stress. The adaptation mechanism could also be applied in oral hygiene by facilitating the fitness and adaptability of the oral commensal streptococci to suppress the pathogens.