New agents against multiresistant gram-negative bacteria

Duration

Jan 01, 2015 - Dec 31, 2018

Coordinator

Jordi Vila

Funded by

Ministerio de Ciencia, Innovación y Universidades. Instituto de Salud Juan Carlos III, Unión Europea. This project is co-funded by the Fondo Europeo de Desarrollo Regional (FEDER). “Una manera de hacer Europa”.

Currently a large partion of available antibiotics are not suitable for the treatment of multiresistant pathogens. Sometimes the choice of treatment is reduced to a single drug, such as colistin for P. aeruginosa and Acinetobacter. The lack of profitability has led to a decline in R+D for new antibiotics by the pharmaceutical industry. There is therefore a clear need for new antibacterial agents, mainly against multi-resistant Gram-negative bacilli. 

The main objective of this project is the design of new antibacterial agents against P. aeruginosa, A. baumannii and K. pneumoniae by various approaches: 

1. Characterization of potential inhibitors of efflux systems, we have found by docking, 50 compounds (from two libraries of compounds) that potentially can inhibit efflux pumps. These compounds will be characterized in detail. 

2. To optimize peptides with activity against the organisms being studied. We have 18 antibacterial peptides with potential capacity and its stability and toxicity will be studied. Of those the three peptides with increased activity and stability and less toxicity, the "in vivo" activity will be investigated; 

3. Characterization of two-component systems (TCS). By analysis "in silico" found 41 potential TCS in A. baumannii. The aim is to study its involvement in virulence and essentiality, in order to find possible inhibitors that would have antibacterial activity and antivirulencia; 

4. Design and study of the antibacterial activity of peptide-oligonucleotide and siderophore-oligonucleotide hybrids. Oligonucleotides inhibit mRNA expression of some essential genes, whereas either peptide or siderophor will be used as transport systems across the cell wall. Once designed these hybrids will be tested both "in vitro" and "in vivo".

Total funding

184,827.50 €

Project Code

PI14/00755