Stress and Bacterial Evolution

Research Summary

We try to understand the genetic mechanisms involved in genome stability in bacteria and their roles on evolution and adaptation. Specifically, we study both stable and induced hypermutation/hyper-recombination as “bacterial strategies” to speed adaptation to environmental stress, including antibiotic challenges. This knowledge may be useful to i) prevent the development of antibiotic resistance in bacterial pathogens (e.g. Escherichia coli, Pseudomonas aeruginosa, Mycobacterium tuberculosis, etc) and ii) to improve prokaryotic species of industrial interest (e.g. Streptomyces).

Research Lines

1. Regulation of hypermutation and hyper-recombination.

• Transcriptional regulation of specialised DNA polymerases (SOS regulon)
• Regulation of mismatch repair
• Effect of antibiotics on bacterial mutation and recombination: antibiotics as promoters of antibiotic resistance?

2. Genetic basis of genome stability in prokaryotes lacking a canonical MutS-MutL-based DNA mismatch repair (MMR) system: we study alternative MMR pathways in these organisms, including most Actinobacteria (e.g. Mycobacterium, Streptomyces, etc) and their effect on the evolvability, including acquisition of antibiotic resistance.
3. Development of hypermutant/hyper-recombinant prokaryotes of industrial interest as biotechnological tools to produce improved biosynthetic or degrading pathways.
4. Preventing emergence and evolution of antibiotic resistance: search and characterize compounds able to inhibit the development of antibiotic resistance (by mutation, recombination and horizontal transfer).

A strain of Mycobacterium in which nucS gene has been eliminated (1) produces a high number of mutants resistant to the antibiotic present in the Petri dish (rifampicin). However, the parental strain (with nucS active) produces much less mutants (2)./ Alfredo Castañeda and Jesús Blázquez, CNB-CSIC.

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