Efflux Mechanisms of Fluoroquinolones and beta-lactams

Table of Contents

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Why efflux ?

Why efflux ?

Why efflux ?

Why efflux ?

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Most antibiotics are amphiphilic !

Most antibiotics are amphiphilic !

Most antibiotics are amphiphilic !

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Identification of efflux pumpsbased on genome sequencing data

Structure of pumps in eucaryotic cells

Structure of pumps in procaryotic cells

Efflux pumps in bacteria:what does it mean for resistance ?

P. aeruginosa seems to be constitutively resistant to many antibiotics ...

Disruption of MexAB-OprM restores the activity of several antibiotics against P. aeruginosa

Efflux pumps in bacteria:what does it mean for resistance ?

Overexpression of efflux pumps in P. aeruginosa upon exposure to fluoroquinolones in CF patients

Overexpression of efflux pumps in P. aeruginosa upon exposure to fluoroquinolones in CF patients

Efflux pumps in bacteria:what does it mean for resistance ?

Efflux in cooperation with other resistance mechanisms

Efflux in cooperation with other resistance mechanisms

Efflux in cooperation with other resistance mechanisms

Overexpression of efflux pumps in P. aeruginosa upon exposure to fluoroquinolones in CF patients

Cooperation of efflux pumps and target mutation in P. aeruginosa in CF patients

PPT Slide

Cooperation of efflux pumps and target mutation in P. aeruginosa in CF patients

Efflux pumps in bacteria:what does it mean for resistance ?

Efflux and selection of resistance to FQ

Efflux and selection of resistance to FQ

Efflux and selection of resistance to FQ

How to cope with efflux pumps in anti-infective therapy ?

MIC considerations ...

Enters the quinolone pmrA efflux pump ...

MIC considerations ...

PK / PD considerations ...

Optimisation based on pharmacodynamics

Optimisation based on pharmacodynamics

How to cope with efflux pumps in anti-infective therapy ?

Topology of the wide spectrum Mex pumps in Pseudomonas (RND superfamily)

Functionning of the wide spectrum Mex pumps in Pseudomonas

Wide spectrum pumps in Pseudomonas

Wide spectrum pumps in Pseudomonas

Wide spectrum pumps in Pseudomonas

Pseudomonas and quinolone efflux

Pseudomonas and penem efflux

Pseudomonas and penem efflux

Pseudomonas and penem efflux

Combined mechanisms of resistance in Pseudomonas

Combined mechanisms of resistance in Pseudomonas

Combined mechanisms of resistance in Pseudomonas

Combined mechanisms of resistance in Pseudomonas

Contribution of resistance mechanisms to carbapenem resistance in Pseudomonas

Contribution of resistance mechanisms to carbapenem resistance in Pseudomonas

Contribution of resistance mechanisms to carbapenem resistance in Pseudomonas

Contribution of resistance mechanisms to carbapenem resistance in Pseudomonas

Contribution of resistance mechanisms to carbapenem resistance in Pseudomonas

Contribution of resistance mechanisms to carbapenem resistance in Pseudomonas

Contribution of resistance mechanisms to carbapenem resistance in Pseudomonas

Contribution of resistance mechanisms to carbapenem resistance in Pseudomonas

An what about ertapenem ?

A burning question ...

Fluoroquinolones-exposed P. aeruginosa overexpress wide spectrum efflux pumps

Mex-expressing strains become highly resistant to many antibiotics

Perspectives:strategies to overcome resistance by efflux: en route to a rational design of efflux pump inhibitors ?

High throughput screening for the discovery of inhibitors of ‘large spectrum’ transporters

High throughput screening for the discovery of inhibitors of ‘large spectrum’ transporters

Shall we have a better future ?

Thank you for your attention ...

Additional questions ….

Why is IMI more affected than MERO by ?OprD ?

Why is MERO more affected than IMI by MexAB ?

Email: tulkens@facm.ucl.ac.be

Home Page: http://www.md.ucl.ac.be/facm/facm-conferences.htm

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