Evolutionary origins of multidrug and drug‐specific efflux pumps in bacteria

• Published in: The FASEB journal 1998-03, Vol.12 (3), p.265-274
• Main Authors: Saier, Milton H., Paulsen, Ian T., Marek, K. sliwinski, Pao, Stephanie S., Ronald, A. skurray, Nikaido, Hiroshi
• Format: Article
• Language: English
• Subjects: antibiotics; antimicrobial agents; ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics; ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism; ATP-Binding Cassette Transporters; Bacteria - genetics; Bacteria - metabolism; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Division; Drug Resistance, Microbial - genetics; Drug Resistance, Multiple - genetics; drugs; Escherichia coli; evolution; Evolution, Molecular; Genome, Bacterial; Humans; Methanococcus jannaschii; Pharmaceutical Preparations - metabolism; phylogenetic trees; resistance; transport
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.12.03.265

The available genomic sequences of three pathogenic and three nonpathogenic bacteria were analyzed to identify known and putative drug‐specific and multidrug resistance transport systems. Escherichia coli was found to encode 29 such pumps, and with the exception of the archaebacterium Meth anococcus jannaschii, the numbers of multidrug efflux pumps encoded within genomes of the other organisms were found to be approximately proportional to their total numbers of encoded transport systems as well as to total genome size. The similar numbers of chromosomally encoded multidrug efflux systems in pathogens and nonpathogens suggests that these transporters have not arisen recently in pathogens in response to antimicrobial chemotherapy. Phylogenetic analyses of the four transporter families that contain drug efflux permeases indicate that drug resistance arose rarely during the evolution of each family and that the diversity of current drug efflux pumps within each family arose from just one or a very few primordial systems. However, although the ability to confer drug efflux appears to have emerged on only a few occasions in evolutionary time and was stably maintained as an evolutionary trait, modulation of the substrate specificities of these systems has occurred repeatedly. A speculative model is presented that may explain the apparent capability of these multidrug transport systems to mediate drug transport from the cytoplasm or directly from the phospholipid bilayer.—Saier, M. H. Jr., Paulsen, I. T., Sliwinski, M. K., Pao, S. S., Skurray, R. A., Nikaido, H. Evolutionary origins of multidrug and drug‐specific efflux pumps in bacteria. FASEB J. 12, 265–274 (1998)