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A peroxide‐induced zinc uptake system plays an important role in protection against oxidative stress in Bacillus subtilis
Author(s) -
Gaballa Ahmed,
Helmann John D.
Publication year - 2002
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1046/j.1365-2958.2002.03068.x
Subject(s) - bacillus subtilis , regulon , catalase , biology , oxidative stress , biochemistry , hydrogen peroxide , efflux , zinc , mutant , oxidative phosphorylation , chemistry , bacteria , gene , genetics , organic chemistry
Summary In Bacillus subtilis , hydrogen peroxide (H 2 O 2 ) induces expression of the PerR regulon including catalase (KatA), alkyl hydroperoxide reductase and the DNA‐binding protein MrgA. We have identified the P‐type metal‐transporting ATPase ZosA (formerly YkvW) as an additional member of the perR regulon. Expression of zosA is induced by H 2 O 2 and repressed by the PerR metalloregulatory protein, which binds to two Per boxes in the promoter region. Physiological studies implicate ZosA in Zn(II) uptake. ZosA functions together with two Zur‐regulated uptake systems and one known efflux system to maintain Zn(II) homeostasis. ZosA is the major pathway for zinc uptake in cells growing with micromolar levels of Zn(II) that are known to repress the two Zur‐regulated transporters. A perR mutant is sensitive to high levels of zinc, and this sensitivity is partially suppressed by a zosA mutation. ZosA is important for resistance to both H 2 O 2 and the thiol‐oxidizing agent diamide. This suggests that increased intracellular Zn(II) may protect thiols from oxidation. In contrast, catalase is critical for H 2 O 2 resistance but does not contribute significantly to diamide resistance. Growth of cells with elevated zinc significantly increases resistance to high concentrations of H 2 O 2 , and this effect requires ZosA. Our results indicate that peroxide stress leads to the upregulation of a dedicated Zn(II) uptake system that plays an important role in H 2 O 2 and disulphide stress resistance.