Biophysical studies of membrane proteins/peptides. Interaction with ...

BINDING OF A QUINOLONE ANTIBIOTIC TO BACTERIAL
PORIN OmpF
IV
BINDING OF A QUINOLONE
ANTIBIOTIC TO BACTERIAL
PORIN OmpF
1. Introduction
Fluoroquinolones (quinolones) have been shown to present broad-spectrum
antimicrobial activity and are currently one of the most successful classes of drugs.
They are reported as relatively well tolerated drugs with reasonably few undesirable
effects (Albini and Monti, 2003; Stahlmann and Lode, 1999), and as a consequence
their therapeutic application is increasing. The antibiotic activity of quinolones is the
outcome of inhibition of a series of important enzymes for chromosome function and
topology (homologous type II topoisomerases, DNA gyrase, and DNA topoisomerase
IV) (Pestova et al., 2000).
First generation quinolones (nalidixic acid) were used in the treatment of
infections caused by Gram-negative bacteria. More recently, new derivatives were
developed with enhanced antibiotic activity against Gram-positive bacteria, namely
Streptococus pneumoniae, responsible for infections in the respiratory system and other
pathologies (Quiniliani et al., 1999). Some of the new generation quinolones are also
apparently effective against multidrug resistant Mycobacterium tuberculosis and were
shown to be useful in the treatment of AIDS patients infected with this pathogen
(Houston and Farming, 1994; Hooper and Wolfson, 1995). These bacteria are resistant
to a wide range of aggressive agents (acid/alcohol) due to the presence of a complex
permeability barrier (Nikaido et al., 1993).
The possible strategies for quinolones entry through the outer and inner
membranes of bacteria are via porin channels (Dechené et al., 1990; Chevalier et al.,
2000), or hydrophobic diffusion through the lipid bilayer. The porin pathway is
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