Molecular characterization of cadmium resistance in Streptococcus thermophilus strain 4134: An example of lateral gene transfer

Two genes (cadC_St and cadA_St [subscript St represents Streptococcus thermophilus]), located on the chromosome of S. thermophilus 4134, were shown to constitute a cadmium/zinc resistance cassette. The genes seem to be organized in an operon, and their transcription is cadmium dependent in vivo. The proposed product of the cadA open reading frame (CadA_St) is highly similar to P-type cadmium efflux ATPases, whereas the predicted protein encoded by cadC_St (CadC_St) shows high similarity to ArsR-type regulatory proteins. The observed homologies and G+C content of this cassette and surrounding regions suggest that this DNA was derived from Lactococcus lactis and may have been introduced relatively recently into the S. thermophilus 4134 genome by a lateral gene transfer event. The complete cassette confers cadmium and zinc resistance to both S. thermophilus and L. lactis, but expression of cadA_St alone is sufficient to give resistance. By using electrophoretic mobility shift assays it was shown that the CadC_St protein is a DNA binding protein that binds specifically to its own promoter region, possibly to two copies of an inverted repeat, and that this CadC_St-DNA interaction is lost in the presence of cadmium. Using lacZ fusion constructs it was shown that the cadmium-dependent expression of CadA_St is mediated by the negative regulator CadC_St. A model for the regulation of the expression of cadmium resistance in S. thermophilus is discussed.