Approach

The approach we have adopted in the ANTIRESDEV project is to carry out longitudinal intervention studies using antibiotics with different modes of action, antimicrobial spectra and pharmacokinetic properties and to identify the antibiotic-resistant strains that arise from their use. The studies involve healthy volunteers and the dynamics (emergence and persistence) of the antibiotic-resistant strains isolated from them and the ecological impact of antibiotic administration on the indigenous microbiota will be subjected to statistical modelling. The genetic basis of resistance in these isolates will be identified using state-of-the-art microarrays and the genetic elements mediating the spread of some of these will be further investigated in order to help characterise their likely mode of transmission. The biological cost to the organisms of developing resistance to one or more antibiotics will be determined as this impinges on the dynamics and transmission of antibiotic resistance throughout the population. In parallel with these culture-based studies, a culture-independent approach (454 pyrosequencing) will also be used to determine the composition of the oral and faecal microbiotas (including not-yet-cultivated members), the full complement of antibiotic resistance determinants (the "resistome") in these communities and the effect of antibiotic administration on these.