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Novel appproaches to detect and circumvent antibiotic resistance in Pseudomonas aeruginosa

Applicant Van Delden Christian
Number 63239
Funding scheme NRP 49 Antibiotic resistance
Research institution Service des Maladies Infectieuses Département de Médecine Interne Hôpital Cantonal - HUG
Institution of higher education University of Geneva - GE
Main discipline Molecular Biology
Start/End 01.10.2001 - 30.09.2006
Approved amount 571'855.00
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Lay Summary (English)

Lay summary
Antibiotic resistance: Detection and circumvention

Pseudomonas aeruginosa is an opportunistic pathogen in humans, notorious for its resistance to antibiotics and dreaded in hospitals. This project is developing new methods for investigating its resistance mechanisms and for novel treatment approaches that weaken its virulence determinants.

Pseudomonads are common inhabitants of soil and water. P. aeruginosa is also an opportunistic pathogen in humans that is primarily a nocosomial pathogen, colonizing intubated and cystic fibrosis patients and able to cause life threatening blood stream infections. Due to its ability to develop resistance to a variety of antibiotics, P. aeruginosa is difficult to treat. New approaches are needed to investigate the emergence of these resistances at the molecular level and to limit the risk of infection.

We are using DNA microarrays (chips) and quantitative PCR-based methods with the aim to trace the resistance mechanisms in P. aeruginosa. Comparison of clinical isolates from patients infected with P. aeruginosa with the corresponding antibiotic treatment will allow us to derive the relationship between the appearance of a resistance mechanism and a particular antibiotic therapy. P. areuginosa produces a great number and a wide array of virulence determinants. In vitro examinations have shown that the production of these factors can be blocked by means of synthetic compounds. We are examining the mechanisms underlying this blocking and seeking to optimise these compounds to reduce the virulence of P. aeruginosa.

Knowledge gained on the resistance mechanisms at the molecular level will be applicable to other pathogens. The results of the study will provide valuable information as to selecting appropriate therapies. This novel approach of seeking to reduce virulence rather than to destroy the pathogens circumvents the antibiotic selection pressure towards resistance development caused by conventional antibiotictreatments. Our work will contribute to lessening the risks of infection and reducing the costs of antibiotic therapies.

Direct link to Lay Summary Last update: 21.02.2013

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