NorM of Vibrio parahaemolyticus apparently is a new type of multidrug efflux protein, with no significant sequence similarity to any known transport proteins. Based on the following experimental results, we conclude that NorM is an Na+-driven Na+/drug antiporter. (i) Energy-dependent ethidium efflux from cells possessing NorM was observed in the presence of Na+ but not of K+. (ii) An artificially imposed, inwardly directed Na+ gradient elicited ethidium efflux from cells. (iii) The addition of ethidium to cells loaded with Na+ elicited Na+ efflux. Thus, NorM is an Na+/drug antiporting multidrug efflux pump, the first to be found in the biological world. Judging from the similarity of the NorM sequence to those of putative proteins in sequence databases, it seems that Na+/drug antiporters are present not only in V. parahaemolyticus but also in a wide range of other organisms.
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