2 HIGHLY SIMILAR MULTIDRUG TRANSPORTERS OF BACILLUS-SUBTILIS WHOSE EXPRESSION IS DIFFERENTIALLY REGULATED

The Bacillus subtilis genome encodes two multidrug efflux transporters sharing 51% sequence identity: Bmr, described previously, and Bit, de scribed here, Overexpression of either transporter in B. subtilis lead s to a similar increase in resistance to ethidium bromide, rhodamine a nd acridine dyes, tetraphenylphosphonium, doxorubicin, and fluoroquino lone antibiotics. However, Bit differs widely from Bmr in its expressi on pattern, Under standard cultivation conditions, B. subtilis express es Bmr but Bit expression is undetectable, We have previously shown th at Bmr expression is regulated by BmrR, a member of the family of MerR -like transcriptional activators, Here we show that blt transcription is regulated by another member of the same family, BltR. The DNA-bindi ng domains of BmrR and BltR are related, but their putative inducer-bi nding domains are dissimilar, suggesting that Bmr and Bit are expresse d in response to different inducers, Indeed, rhodamine, a substrate of Bmr and Bit and a known inducer of Bmr expression, does not induce Bi t expression, Bit expression has been observed only in B. subtilis car rying mutation acfA, which, as we show here, alters the sequence of th e bit gene promoter. Unlike bmr, which is transcribed as a monocistron ic mRNA, bit is cotranscribed with a downstream gene encoding a putati ve acetyltransferase, Overall, the differences in transcriptional cont rol and operon organization between bmr and blt suggest that the trans porters encoded by these genes have independent functions involving th e transport of distinct physiological compounds.