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Inhibiting Pseudomonas aeruginosa, a multidrug resistant pathogen

Patricia Saenz-Méndez. From: UdelaR, Montevideo, Uruguay, to: University of Gothenburg.

Project abstract

Antibiotic resistance is one of the most serious health threats. Infections from resistant bacteria are increasingly common, and some pathogens have become resistant to multiple types of antibiotics. We need aggressive actions to fight aggressive resistant bacteria. Thus, the current challenge of antimicrobial drug research is the identification of novel drug targets, avoiding the development of resistance. Pseudomonas aeruginosa is a well-known opportunistic multidrug resistant pathogen responsible for millions of deaths per year around the world. Exotoxin A (ETA) is the most potent toxin produced by P. aeruginosa, catalyzing the transfer of an ADP-ribose moiety to the eukaryotic elongation factor 2 (eEF2) in cells of the infected tissue. This modification leads to a dysfunction in the host protein synthesis with eventual cell death. Targeting P. aeruginosa ETA with small molecule inhibitors will disrupt the pathogen´s virulence providing the starting point for new antimicrobial drug development. As the pathogen is not directly attacked, the defense machinery will not be triggered, and hence such new antibiotics will unlikely lead to development of drug resistance. Focusing research efforts on new types of targets (ETA) detached from the pathogen, and using new strategies such as bioinformatics, will allow the generation of new antimicrobial drugs that contributes in the ongoing fight against infectious diseases.

Project Summary Results

Antibiotic resistance is one of the most serious health threats. Infections from resistant bacteria are increasingly common, and some pathogens have become resistant to multiply types of antibiotics. We need aggressive actions to fight aggressive resistant bacteria. Thus, the current challenge of antimicrobial drug research is the identification of novel drug targets, avoiding the development of resistance. Pseudomonas aeruginosa is a well-known opportunistic multidrug resistant pathogen responsible for millions of deaths per year around the world. Exotoxin A (ETA) is the most potent toxin produced by P. aeruginosa, which alters the eukaryotic elongation factor 2 (eEF2) in cells of the infected tissue. This modification leads to a dysfunction in the host protein synthesis with eventual cell death. Targeting P. aeruginosa ETA with small molecule inhibitors will disrupt the pathogen's virulence providing the starting point for new antimicrobial drug development. As the pathogen is not directly attacked, the defense machinery will not be triggered, and hence such new antibiotics will unlikely lead to development of drug resistance.

We have used new strategies such as bioinformatics, focusing our research efforts on developing new antimicrobial drugs against new types of targets (ETA) detached from the pathogen. Also, we have developed a computational methodology allowing for detecting several targets at the same time. This might lead to new antimicrobial agents fighting against different pathogens in addition to Pseudomonas aeruginosa, such as those responsible for diphtheria and cholera. Developing of new potential antibiotics with reduced (or even non-existent) trends to generate resistance will contribute in the ongoing fight against infectious diseases.

Senast uppdaterad: 2018-04-11 13:09