Final Report Summary - PNEUMOPEP (New methods of treatment of antibiotic-resistant pneumococcal disease)
The project was undertaken in response to the need to find new methods of treatment of disease due to Streptococcus pneumoniae. This bacterium is a major cause of community-acquired pneumonia, meningitis, bacteraemia and otitis media and it exhibits high rates of multi-drug resistance in countries worldwide. More than ever before modern drug discovery is dependent on high-throughput screening. Therefore, the drug discovery process is shifting focus from identifying suitable candidate drugs - which remains an essential but time-consuming goal - to identifying suitable lead compounds in order to maximise the cost-effectiveness and speed of the subsequent lead optimisation process.
Antibiotic resistance in the pneumococcus is a continuing and growing problem. The high rate of mortality and neurological injury in pneumococcal meningitis emphasises the urgency for new powerful therapeutic interventions, in addition to antimicrobial therapy. This project brings together a trans-European multidisciplinary consortium to develop new approaches to these problems. The consortium brings together a collection of complementary skills to provide new lead compounds and new methods of compound delivery in the treatment of pneumococcal diseases.
The innovative aspects of the project were:
Two completely new targets for anti-pneumococcal therapy. These are the pneumococcal toxin, pneumolysin and pneumococcal cell surface proteinases. These proteins have not been used before as targets but there is considerable evidence substantiating their validity as targets and much of this evidence has been gathered in the laboratories of two of the participants in this project (partner 1 and 2):
- peptides as lead compounds for the treatment of pneumococcal diseases;
- small molecules as lead compounds for the treatment of pneumococcal diseases;
- chitosan for the nasal delivery of anti-pneumococcal agents;
- the lead compounds will have the potential to prevent the neurological sequelae associated with pneumococcal meningitis.
The PNEUMOPEP project achieved its overall aim of finding lead compounds for treatment of pneumococcal diseases. Six molecules inhibited pneumolysin and were effective in vivo and on was found that acted against pneumococcal neuraminidase A.
Antibiotic resistance in the pneumococcus is a continuing and growing problem. The high rate of mortality and neurological injury in pneumococcal meningitis emphasises the urgency for new powerful therapeutic interventions, in addition to antimicrobial therapy. This project brings together a trans-European multidisciplinary consortium to develop new approaches to these problems. The consortium brings together a collection of complementary skills to provide new lead compounds and new methods of compound delivery in the treatment of pneumococcal diseases.
The innovative aspects of the project were:
Two completely new targets for anti-pneumococcal therapy. These are the pneumococcal toxin, pneumolysin and pneumococcal cell surface proteinases. These proteins have not been used before as targets but there is considerable evidence substantiating their validity as targets and much of this evidence has been gathered in the laboratories of two of the participants in this project (partner 1 and 2):
- peptides as lead compounds for the treatment of pneumococcal diseases;
- small molecules as lead compounds for the treatment of pneumococcal diseases;
- chitosan for the nasal delivery of anti-pneumococcal agents;
- the lead compounds will have the potential to prevent the neurological sequelae associated with pneumococcal meningitis.
The PNEUMOPEP project achieved its overall aim of finding lead compounds for treatment of pneumococcal diseases. Six molecules inhibited pneumolysin and were effective in vivo and on was found that acted against pneumococcal neuraminidase A.