Lsr2 of Mycobacterium Represents a Novel Class of H-NS-Like Proteins

Lsr2 is a small, basic protein present in Mycobacterium and related actinomycetes. Our previous in vitro biochemical studies showed that Lsr2 is a DNA-bridging protein, a property shared by H-NS-like proteins in gram-negative bacteria. Here we present in vivo evidence based on genetic complementation experiments that Lsr2 is a functional analog of H-NS, the first such protein identified in gram-positive bacteria. We show that lsr2 can complement the phenotypes related to hns mutations in Escherichia coli , including β-glucoside utilization, mucoidy, motility, and hemolytic activity. We also show that Lsr2 binds specifically to H-NS-regulated genes and the repression of hlyE by Lsr2 can be partially eliminated by overexpression of slyA , suggesting that the molecular mechanisms of Lsr2 repression and depression are similar to those of H-NS. The functional equivalence of these two proteins is further supported by the ability of hns to complement the lsr2 phenotype in Mycobacterium smegmatis . Taken together, our results demonstrate unequivocally that Lsr2 is an H-NS-like protein.