Resistance to β-lactam antibiotics

Description β-lactam antibiotics are a broad class of antibiotics that are used on a large-scale. We are studying the enzyme TEM-1 β-lactamase which plays a major role in the development of antibiotic resistance. Bacteria that carry the original enzyme TEM-1 are highly resistant to penicillin. New antibiotics have been developed to which TEM-1 does not confer clinical resistance. One of these is the antibiotic cefotaxime. Several mutations in TEM-1 are known to increase cefotaxime resistance. We would like to study whether (1) these mutations have a trade-off with the original function of the enzyme (breaking down penicillin) and (2) whether resistance to other β-lactams increases or decreases after the incorporation of these mutations.

Used skills: Basic molecular techniques, including PCR, cloning into expression vectors, transformation to bacterial hosts, restriction and sequence analysis; MIC assays; simple bioinformatics and statistical analysis to interpret evolved enzymes.

Requirements: Molecular and Evolutionary Ecology (GEN20304) and Genetic Analyses Tools and Concepts (GEN30306) are a good preparation.

Reference: Soskine M, Tawfik DS (2010) Mutational effects and the evolution of new protein functions. Nat Rev Genet 11: 572-582.