In the PBE lab we study the role of plasmids as catalysts of bacterial evolution, with a special focus on the evolution of plasmid-mediated antibiotic resistance.

Currently, we have two ongoing projects:

– In vivo evolution of plasmid-mediated resistance.

Conjugative plasmids play a key role in the horizontal spread of antibiotic resistance mechanisms among bacteria. One of the key factors undermining the successful spread of a conjugative plasmid is the initial fitness cost produced by the plasmid in the recipient bacteria. The factors involved in this cost and its potential compensation remain largely unknown. In our lab we are trying to understand the evolutionary and genetic determinants that promote the emergence and establishment of successful associations between bacterial clones and resistance plasmids in vivo.

To do so we study conjugation events between different enterobacteria occurring in the gut of hospitalized patients. We study the cost produced by the plasmids when they first infect the bacterial clone and the coevolution of plasmid and bacteria over time, both in vivo and in vitro. With this work we are trying to understand what determines a successful plasmid-bacteria association. Our results will help to predict and hopefully prevent the spread of clinically relevant plasmid-bacteria associations.

Projects 1

– The role of multicopy plasmids in bacterial evolution.

Plasmids can be generally divided into large plasmids (ca. > 15 kb) that have relatively few copies per bacterial cell, and small plasmids (ca. < 15 kb) that have many copies per cell. Large conjugative plasmids have played an important role in the spread of antibiotic resistance and they have been extensively studied over the last few decades. Small multicopy plasmids are also very common in prokaryotes, but their role in bacterial biology and evolution is poorly understood. The multicopy nature of these plasmids is associated with an increase in gene dosage for the genes they code, and that has at least two relevant outcomes: (i) an increase in gene expression and (ii) an increase in gene evolvability.

In our lab we investigate the possible evolutionary advantages associated with carrying a beneficial gene on a multicopy plasmid, versus to be located on the chromosome. We are using a multidisciplinary approach combining experimental evolution, whole genome sequencing and mathematical modelling to better understand the biological role of these small replicons.

Projects 2