of the appearance of resistance to beta-lactam antibiotics in Streptococcus
pneumoniae: exploring strategies based on microbial ecology
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.
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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
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.
October 1998 September 2000
Instituto Nacional de la Salud
Consejo Superior de Investigaciones Científicas
Glaxo Wellcome SpA
Universität Kaiserslautern (DE)
Centre National de Recherche Scientifique (CNRS)