IJUP08 - Universidade do Porto

Microbiological study of the interaction of Outer Membrane
Proteins with antibiotics
M. Garrido 1 , P. Gameiro 1,2 , P.J. Eaton 2 and M. Feio 1,2
1 Department of Chemistry, Faculty of Science, University of Porto, Portugal.
2 REQUIMTE
Pathogen resistance to antibiotics due to their extensive use is posing a major problem to
public health. Research into better and improved drugs is therefore a primary concern in
this filed.
This work is part of a wider project that has the final goal of understanding, at the
molecular level, the uptake of antibiotics through porins – channel proteins – that have a
crucial role not only in the transport of certain antibiotic families but also in the
development of resistance. Specifically, it is intended to obtain detailed information about
the molecular interactions of antibiotics belonging to the fluoroquinolone family and
OmpF. This membrane protein is known to be associated with the transport of these drugs
and it is important to understand the interdependence between the transport mechanism and
the drug’s efficiency 1,3 .
The microbiological study of the effect of fluoroquinolones upon a collection of E. coli
strains 2 with mutations in their OmpF channels is being carried out. The microplate minimum
inhibitory concentrations (MIC) method is being used to screen the effect of moxifloxacin in order
to elucidate the mechanism of cellular transport. Binary and ternary complexes of copper(II) and
1,10-phenantroline with moxifloxacin will also be tested for the improved efficacy attributed to
metalloantibiotics 1 .
Atomic Force Microscopy (AFM) will also be used to complement the study of the action
for the different drugs in the different E. coli strains allowing the observation of their effect
at a morphologic level.
References:
[1] Gameiro, P., Rodrigues, C., Baptista, T., Sousa, I., Castro, B. (2007), Solution studies on binary
and ternary complexes of copper(II) with some fluoroquinolones and 1,10-phenanthroline:
antimicrobial activity of ternary metalloantibiotics, International Journal of Pharmaceutics, 334,
129-136.
[2] Prilipov, A., Phale, P., Van Gelder, P., Rosenbusch, J., Koebnik, R. ( 1998), Coupling sitedirected
mutagenesis with high-level expression: large scale production of mutant porins from E.
coli, FEMS Microbiology Letters, 163, 65-72.
[3] Neves, P., Berkane, E., Gameiro, P., Winterhalter, M., Castro, B. (2005), Interaction between
quinolones antibiotics and bacterial outer membrane porin OmpF, Biophysical Chemistry, 113,
123-128.
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