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Multidrug efflux pumps play an important role as a self-defense system in bacteria. Bacterial multidrug efflux pumps are classified into five families based on structure and coupling energy: resistance−nodulation−cell division (RND), small multidrug resistance (SMR), major facilitator (MF), ATP binding cassette (ABC), and multidrug and toxic compounds extrusion (MATE). We cloned a gene encoding a MATE-type multidrug efflux pump from  Streptococcus pneumoniae  R6, and designated it  pdrM . PdrM showed sequence similarity with NorM from  Vibrio parahaemolyticus , YdhE from  Escherichia coli,  and other bacterial MATE-type multidrug efflux pumps. Heterologous expression of PdrM let to elevated resistance to several antibacterial agents, norfloxacin, acriflavine, and 4′,6-diamidino-2-phenylindole (DAPI) in  E. coli  KAM32 cells. PdrM effluxes acriflavine and DAPI in a Na + - or Li + -dependent manner. Moreover, Na +  efflux via PdrM was observed when acriflavine was added to Na + -loaded cells expressing  pdrM . Therefore, we conclude that PdrM is a Na + /drug antiporter in  S. pneumoniae . In addition to  pdrM , we found another two genes, spr1756 and spr1877,that met the criteria of MATE-type by searching the  S. pneumoniae  genome database. However, cloned spr1756 and spr1877 did not elevate the MIC of any of the investigated drugs. mRNA expression of spr1756, spr1877, and  pdrM  was detected in  S. pneumoniae  R6 under laboratory growth conditions. Therefore, spr1756 and spr1877 are supposed to play physiological roles in this growth condition, but they may be unrelated to drug resistance.

Functionally Cloned pdrM from Streptococcus pneumoniae Encodes a Na+ Coupled Multidrug Efflux Pump