All living organisms from bacteria to mammals extrude noxious compounds to the external medium. When exposed to antibiotics, bacteria actively extrude intracellular antibiotic and develop resistance to the drug. Nosocomial Staphylococcus aureaus, Pseudomonas aeruginosa and other bacteria are resistant to a broad range of antibiotics and to structurally and functionally diverse chemotherapeutic agents and disinfectants. For this reason nosocomial infections are especially hard to treat in immunocompromised patients who may be infected by low-virulence bacteria. Extrusion-related antibiotic resistance in P. aeruginosa arises by the expression of Mex-extrusion pumps, including genetically distinct mexA-mexB-oprM, mexC-mexD-oprj, and mexE-mexF-oprN systems, each encoding two inner membrane proteins and one outer membrane protein. S. aureus becomes resistant to fluoroquinolone by expressing NorA extrusion proteins and to disinfectants by expressing Qac extrusion proteins. The drug extrusion machinery may be classified into several categories according to the number of transmembrane segments it exhibits. The proteins that belong to a major facilitator super family have 12 or 14 transmembrane segments. The extrusion proteins with molecular weight of 12,000 to 15,000 span the membrane 4 times and are collectively called small multidrug resistance proteins. The extrusion proteins that transport substrate across the inner and outer membrane of gram-negative bacteria are in the resistance nodulation cell division family.
Keywords: MDR; antibiotic; bacterial membrane; diffusion; drug resistance; efflux; extrusion; membrane protein.
Copyright © 1997 Japanese Society of Chemotherapy and the Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.