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ANTIRESDEV


The effects of antibiotic administration on the emergence and persistence of antibiotic-resistant bacteria in humans and on the composition of the indigenous microbiotas at various body sites
EC contribution
: € 5,368,088
Duration
: 36 months
Starting date
: 01/11/2009
Funding scheme
: Focused research project
Keywords
: antibiotic resistance, genetic determinants, microarrays, fitness cost, ecology, resistome, pyrosequencing, indigenous microbiota, metagenomics
Contract/Grant agreement number :
: 241446
Project web-site
: http://www.ucl.ac.uk/antiresdev

Summary:

The objective of the HEALTH-2009-2.3.1-2 call is to study the impact of different antibiotics on the prevalence of resistant bacteria in the human host. In ANTIRESDEV this objective will be achieved as follows. We will use culture-based and culture-independent approaches to investigate the impact of four different types of antibiotics (with different modes of action, antimicrobial spectra and pharmacokinetic properties) on the emergence of antibiotic-resistant organisms and their persistence at several body sites. Disruption of the indigenous microbiota is recognized as an important factor in the persistence and transmission of antibiotic-resistant organisms, therefore we will also study the ecological impact of the antibiotics on the indigenous microbiotas of several body sites using culture-dependent and -independent techniques. We will then identify, using state-of-the-art microarrays, the genes responsible for resistance in the antibiotic-resistant organisms isolated. The genetic elements involved in resistance transfer by a number of these organisms will also be determined as knowledge of these elements is essential to fully understand the mechanisms underlying resistance transmission. We will use state-of-the-art 454 pyrosequencing to determine the full complement of resistance genes (the resistome) present in cultivable and not-yet-cultivated members of the oral and faecal microbiotas and the effect on these resistomes of antibiotic administration. Another important aspect of the dynamics and transmission of resistance is the fitness cost associated with resistance acquisition by an organism and we will investigate this in a number of clinically-important organisms. We will ensure that the results of this study are made available to appropriate governmental and healthcare agencies so that they can be used to help in the formulation of measures designed to reduce the spread of antibiotic resistance.


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