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EC-sponsored Research on Safety of Genetically Modified Organisms - A Review of Results
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image Prevention of the appearance of resistance to beta-lactam antibiotics in Streptococcus pneumoniae: exploring strategies based on microbial ecology

Background and objectives

Penicillins and other beta-lactam antibiotics have made an enormous contribution to human health. However, vast quantities of these antibiotics have been and are continuing to be consumed (more than 1 ton every day in some European countries). This is leading to substantial changes in microbial ecology, with the selection and spread of resistant strains of bacteria. Furthermore, no new family of antibiotics has been brought to routine clinical application during the last 20 years. The result is that there are a growing number of cases of bacterial infection resistant to treatment with known antibiotics, and no new antibiotics becoming available which can be used to replace the now less effective older drugs. In addition, vaccination against bacterial diseases, for example against respiratory pathogens, may also have undesirable ecological consequences. Indeed, it can be argued that because it has produced useful and widely used drugs, the pharmaceutical industry has created an environmental health problem. New innovative strategies are required to control these antibiotic-resistant pathogens. In line with the proposals concerning the new "industrial ecology", work is required to develop measures to counteract environmental damage, and the measures need to be applied urgently.

Approach and methodology

This project aims to explore the some of the possibilities afforded by biotechnology in the field of microbial ecology. One of the most pressing problems in current antibiotic therapy is being used as an example: infections caused by the ubiquitous Streptococcus pneumoniae. Despite its clinical importance, the microbial ecology of streptococcal populations remains poorly understood. This project is investigating the ecological and environmental factors regulating clonal selection, colonisation, bacterial interference and horizontal gene transfer.

Main findings and outcome

The project, in its early stages, will provide a better description of the microbial ecology of Streptococcus pneumoniae. It will generate a collection of minimal Streptococcus genomes, and analyse their characteristics and fate in various animal models, using a marker gene (the gene for green fluorescent protein). In this way, the characteristics and properties of colonisation and horizontal gene transfer will be elucidated


A thorough understanding of the genetics and ecology of a bacterium causing respiratory disease, Streptococcus pneumoniae, will help in the fight against the growing problem of antibiotic resistance in clinical practice. The project may identify new targets allowing the development of novel antibiotics, particularly those interfering with the acquisition of antibiotic resistance. It could also lead to the possibility of creating biotherapeutic or biorestorative strains of non-pathogenic bacteria.

Major publications

Hakenbeck R., “Transformation in Streptococcus pneumoniae”.
Res. Microbiol.,
151, 2000, pp.453-456.

Reichmann P. and Hakenbeck R., “Allelic Variation in a Peptide-Inducible Two-Component System of Streptococcus pneumoniae”.
FEMS Microbiol Lett.,
190, 2000, pp. 231-236.

Nieto C., Acebo P., Frenández de Palencia P., Corrales M.A., Espinosa M. and López P., Procedimiento de obtención y detección de bacterias gram-positivas fluorescentes, Spanish Patent Application n° 9901813, CSIC, Spain, 1999.

Nieto C., Frenández de Palencia P., López P. and Espinosa M., “Construction of a tightly regulated plasmid vector for Streptococcus pneumoniae: Controlled Expression of the Green Fluorescent Protein”.
43, 2000, pp. 205-213.

Acebo P., Nieto C., Corrales M.A., Espinosa M. and López P., “Quantitative detection of Streptococcus pneumoniae cells harbouring single or multiple copies of the gene encoding the green fluorescent protein”.
Microbiology, 146, 2000, pp. 1267-1273.
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Contract number

October 1998 – September 2000

F. Baquero
Instituto Nacional de la Salud
Madrid (ES)



P. Lopez,
J.C. Alonso

Consejo Superior de Investigaciones Científicas
Madrid (ES)

H. Mott
Glaxo Wellcome SpA
Verona (IT)

R. Hakenbeck
Universität Kaiserslautern (DE)

J-P. Claverys
Centre National de Recherche Scientifique (CNRS)
Toulouse (FR)

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