Abstract
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.
Highlights
Streptococcus pneumoniae is the most common pathogenic bacterium in community-acquired pneumonia [1,2,3,4,5]
This bacterium colonizes the upper respiratory tract and sometimes causes pneumonia, but it is responsible for acute otitis media, bacteremia, and bacterial meningitis [10]. b-lactams and macrolides are usually used to treat S. pneumoniae infections, but the recent increase in the prevalence of antibiotic-resistant S. pneumoniae is a serious problem in clinical sites worldwide [8,11,12,13,14,15,16]
Functional Cloning of pdrM We cloned genes relating to drug resistance from S. pneumoniae
Summary
Streptococcus pneumoniae is the most common pathogenic bacterium in community-acquired pneumonia [1,2,3,4,5]. Several mechanisms contribute to bacterial resistance to drugs: 1) inactivation of drugs by degradation or modification, 2) modification of drug targets, 3) emergence of a bypass mechanism that is not inhibited by drugs, 4) changes in membrane permeability for drugs, and 5) drug efflux from cells. Among these five mechanisms, drug efflux, especially multidrug efflux, is known to play an important role in multidrug resistance in bacteria [19,20,21,22]
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