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Development of metallo-enzyme inhibitors to overcome Pseudomonas aeruginosa antibiotic-re
Author(s) : Gemma S, Brogi S, Brindisi M, Vallone A, De Luca F, Docquier JD
Address : Department of Biotechnology, Chemistry, and Pharmacy, Department of Medical Biotechnology, University of Siena, Italy.
University of Siena

Background. Pseudomonas aeruginosa is the most dominant pathogen associated with adverse clinical outcomes in patients with cystic fibrosis (CF). Anti-pseudomonal β-lactams are the mainstay of therapy for the treatment of chronic P. aeruginosa lung infections CF patients. Unfortunately, this pathogen becomes increasingly resistant to available antibiotics and the global dissemination of multidrug resistant P. aeruginosa strains with acquired carbapenemase genes is a public health concern. 

Hypothesis and objectives. One important mechanism of resistance to β-lactams is the production of one or more β-lactamase(s), belonging to either the active serine enzymes or the metallo-β-lactamases (MBLs), which efficiently inactivate these antibiotics. Acquired MBLs are important resistance factors in P. aeruginosa, conferring resistance to most β-lactams, including the last-resort carbapenems. Considering the increasing prevalence of MBL-producing strains in CF patients (as high as >50% in some settings), our goal is to perform the preclinical investigation and optimization of MBLs inhibitors to be used in combination with currently-available β-lactam antibiotics

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