Project A2

Predicting evolutionary pathways to β-lactam

Joachim Krug, U Cologne | web | email

Arjan de Visser, Wageningen University | web | email

This project has a multi-level research agenda on drug resistance evolution. By a combination of theoretical modeling and laboratory evolution experiments, we aim at making concrete predictions about the evolution of resistance to β-lactam antibiotics. We focus on the relationship between genotype, phenotype, and fitness, including social interactions influencing resistance evolution.

Predictability in Evolution

Collaborative Research Center 1310


Population size mediates the contribution of high-rate and large-benefit mutations to parallel evolution

Schenk M.F., Zwart M.P., Hwang S., Ruelens P., Severing E., Krug J., de Visser J.A.G.M., Nat Ecol Evol, 3. March 2022,

Antibiotic Breakdown by Susceptible Bacteria Enhances the Establishment of β-Lactam Resistant Mutants

Saebelfeld M., Das S.G., Brink J., Hagenbeek A., Krug J., de Visser J.A.G.M., Frontiers in Microbiology, 12: 698970., 19. Auguts 2021,

Choice of β-Lactam Resistance Pathway Depends Critically on Initial Antibiotic Concentration

Ruelens P., de Visser J.A.G.M., Antimicrob. Agents Chemother. 65:e00471-21, 16. July 2021,

Clonal Interference and Mutation Bias in Small Bacterial Populations in Droplets

Ruelens P., de Visser J.A.G.M., Genes 2021, 12(2), 223, 4. February 2021,

The fitness landscapes of translation

Josupeit M., Krug J., Physica A 569, 125768 (2021), 18. January 2021,

Distribution of the number of fitness maxima in Fisher's geometric model

Park S.C., Hwang S. and Krug J., J. Phys. A: Math. Theor. 53 385601, 21. August 2020,

Predictable properties of fitness landscapes induced by adaptational tradeoffs

Das S.G., Direito S.O.L., Waclaw B., Allen R.J., Krug J., elife 9, e55155 (2020), 19. May 2020,

Recombination and mutational robustness in neutral fitness landscapes

Klug A., Park S.C, Krug J., PLoS Comput Biol 15(8): e1006884., 15. August 2019,

Rare beneficial mutations cannot halt Muller's ratchet in spatial populations

Park S.-C., Klatt P., Krug J., EPL 123: 48001, 3. September 2018,

The utility of fitness landscapes and big data for predicting evolution

de Visser, J. A. G. M., Santiago F. E., Fragata I., Matuszewski S., Heredity 121: 401–405, 20. August 2018,

Ecology dictates evolution? About the importance of genetic and ecological constraints in adaptation

de Vos M. G. J., Schoustra S. E., de Visser J. A. G. M., EPL 122: 58002, 17. July 2018,

Unraveling the causes of adaptive benefits of synonymous mutations in TEM-1 β-lactamase

Zwart M. P., Schenk M. F., Hwang S., Koopmanschap B., de Lange N., van de Pol L., Nga T. T. T., Szendro I. G., Krug J., de Visser J. A. G. M., Heredity 121: 406–421, 2. July 2018,

Universality Classes of Interaction Structures for NK Fitness Landscapes

Hwang S., Schmiegelt B., Ferretti L., Krug J., J Stat Phys 172: 226, 13. February 2018,

Local Fitness Landscapes Predict Yeast Evolutionary Dynamics in Directionally Changing Environments

Gorter F. A., Aarts M. G. M, Zwaan B. J., de Visser J. A. G. M., Genetics 208: 307-322, 1. January 2018,

Adaptive benefits from small mutation supplies in an antibiotic resistance enzyme

Salverda M. L. M., Koomen J., Koopmanschap B., Zwart M. P., de Visser J. A. G. M., Proc. Natl. Acad. Sci. USA 114: 12773-12778, 13. November 2017,