IDENTIFICATION OF A ZINC-SPECIFIC METALLOREGULATORY PROTEIN, ZUR, CONTROLLING ZINC TRANSPORT OPERONS IN BACILLUS-SUBTILIS

Zinc is an essential nutrient for all cells, but remarkably little is known regarding bacterial zinc transport and its regulation. We have i dentified three of the key components acting to maintain zinc homeosta sis in Bacillus subtilis. Zur is a metalloregulatory protein related t o the; ferric uptake repressor (Fur) family of regulators and is requi red for the zinc-specific repression of two operons implicated in zinc uptake, yciC and ycdHIyceA. A zur mutant overexpresses the 45-kDa Yci C membrane protein, and purified Zur binds specifically, and in a zinc -responsive manner, to an operator site overlapping the yciC control r egion. A similar operator precedes the ycdH-containing operon, which e ncodes an ABC transporter. Two lines of evidence suggest that the ycdH operon encodes a high-affinity zinc transporter whereas YeiC may func tion as part of a lower-affinity pathway. First, a ycdH mutant is impa ired in growth in low-zinc medium, and this growth defect is exacerbat ed by the additional presence of a yciC mutation. Second, mutation of ycdH, but not yciC, alters the regulation of both the yciC and ycdH op erons such that much higher levels of exogenous zinc are required for repression. We conclude that Zur is a Fur-like repressor that controls the expression of two zinc homeostasis operons in response to zinc. T hus, Fur-like regulators control zinc homeostasis in addition to their previously characterized roles in regulating iron homeostasis, acid t olerance responses, and oxidative stress functions.