Chapter 15. Transport of Antibiotics into Bacteria

Abstract

This chapter discusses the recent researches on transport of antibiotics into bacteria. The aminoglycoside-aminocyclitol (AGAC), a group of antibiotics, comprises a large number of clinically useful drugs that are able to enter both gram-positive and gram-negative bacteria to interfere with protein synthesis. The beta-lactams antibiotics are located on the surface of bacterial cytoplasmic membranes. Therefore, in gram-negative organisms, these antibiotics must cross the bacterial outer membrane to exert their inhibitory effects. The majority of beta-lactams cross the outer membrane by passive diffusion through porin channels. Pseudomonas aeruginosa is intrinsically resistant to most beta-lactams, a situation resulting from poor uptake of drug molecules, across the outer membrane. On the other hand the cephalosporin E-0702 and other catechol bearing structures are transported across the bacterial outer membrane by the tonB-dependent iron transport system. Structure-activity studies have showed that the tonB-dependent transport system is relatively tolerant of chemical variability in the substrate. Transport of mupirocin antibiotic into B. subtilis and S. aureus has been recently investigated. Most quinolones are low molecular-weight hydrophilic molecules. These properties imply that the drugs could well cross the outer membrane through porin channels. Quinolones are indeed known to penetrate the outer membrane of E. coli through OmpF and OmpC porins. The design of novel antibacterial agents that can utilize existing bacterial transport systems for entry into bacteria is an attractive prospect for the therapy of infectious diseases.