Understanding drug synergy and rational design of drug combinations: an integrated approach to combat antimicrobial resistance

Dimitrios Evangelopoulos (primary)
Microbial Diseases, Eastman Dental Institute
Teresa Cortes (secondary)
Department of Infection Biology


Antibiotic resistance is one of the biggest public health challenges of our time. With a limited number of new drugs being developed, it is important to identify ways to maximise the lifetime of the existing drugs. The use of combinatory drug regimens has been proposed to be an attractive solution to the treatment of antibiotic resistant infections. This project will investigate the molecular and cellular mechanisms of synergistic drug combinations using a combination of microbiology, omics and bioinformatic approaches to characterise the fundamental aspects of combinatory drug treatment that can then guide rational design of future drug combinations.


1 Tyers M & Wright DG. Drug Combinations: A Strategy to Extend the Life of Antibiotics in the 21st Century. Nat Rev Microbiol, 2019, 17(3):141-155
2 Evangelopoulos D, Prosser GA, Rodgers A, Dagg MB, Khatri B, Ho MM, Gutierrez MG, Cortes T, de Carvalho LPS. Comparative fitness analysis of D-cycloserine resistant mutants reveals both fitness-neutral and high-fitness cost genotypes. Nat Commun 2019, 10, 4177
3 Federico Fenaroli, James D Robertson, Edoardo Scarpa, Virginia M Gouveia, Claudia Di Guglielmo, Cesare De Pace, Philip M Elks, Alessandro Poma, Dimitrios Evangelopoulos, Julio Ortiz Canseco, Helen M Marriott, David H Dockrell, Simon Foster, Timothy D. McHugh, Stephen A. Renshaw, Josep Samitier Marti, Giuseppe Battaglia, and Loris Rizzello. Polymersomes Eradicating Intracellular Bacteria. ACS Nano Just Accepted Manuscript. DOI: 10.1021/acsnano.0c01870
4 Switzer A, Evangelopoulos D, Figueira R, de Carvalho LPS, Brown D, Wigneshweraraj S. A novel regulatory factor affecting the transcription of methionine biosynthesis genes in Escherichia coli experiencing sustained nitrogen starvation. Microbiology 2018, 164(11):1457-1470
5 Chiner-Oms Á, Berney M, Boinett C, González-Candelas F, Young DB, Gagneux S, Jacobs WR, Parkhill J, Cortes T, Comas I. Genome-wide mutational biases fuel transcriptional diversity in the Mycobacterium tuberculosis complex. Nat Commun 2019, 10, 3994

Genes, development and STEM* approaches to biology
Area of Biology
Techniques & Approaches
BiochemistryBioinformaticsGeneticsMathematics / StatisticsMolecular Biology