RESEARCH SUMMARY

The major interest of the group is to understand the bacterial responses to stress. We specifically study hypermutation and hyperrecombination as bacterial “strategies” to speed adaptation to environmental stresses.

One of the models used here is antibiotic stress and the development of antibiotic resistance. Our work is focused on both stable and inducible hypermutation/hyperrecombination in E. coli, P. aeruginosa and M. smegmatis/tuberculosis.

We are currently studying:

1.- Compensation of stable hypermutation. Once adapted, hypermutable bacteria must decrease (compensate) the high mutation rate to avoid accumulation of deleterious mutations. Our study aims to unveil the molecular mechanisms involved in such a compensation.

2.- Regulation of stress responses and inducible hypermutation.

• Environmental regulation of mutagenesis.

• Transcriptional regulation of specialized DNA-polymerases (belonging to the SOS regulon).

• Effect of antibiotics on mutation and recombination. Antibiotics as promoters of antibiotic resistance.

3.- Hypermutation in bacteria lacking Mismatch Repair System (MMR) such as Mycobacterium and Streptomyces. This will allow the use of hypermutant/hyperrecombinant bacteria of industrial interest as biotechnological tools to produce modified biosynthetic pathways.

4.- Evolution of resistance to beta-lactam antibiotics and the development of new inhibitors of beta-lactamases.

5.- Molecular bases of bacterial evolution. Combating antibiotic resistance by preventing evolution (mutation, recombination and horizontal transfer).