Figure 6. The TEM-family of $\beta$-lactamase contributes to antibiotic resistance problems in hospitals.

The fitness graph shows a four-locus system consisting of the wild type, TEM-1, the quadruple mutant, TEM-50, and all intermediate mutants, including six clinically found mutants in the TEM family. The mutation M69L corresponds to $1000$, E104K to $0100$, G238S to $0010$, and N276D to $0001$. Growth rates were measured for the 16 genotypes under exposure to the antibiotic FEP Cefepime, and the fitness graph was determined accordingly (Mira et al., 2015). The graph reveals higher order epistasis.