Constructs containing all possible combinations of the four mutations found in <i>bla</i>_TEM-50 and <i>bla</i>_TEM-85.

<p>Constructs containing all possible combinations of the four mutations found in <i>bla</i>_TEM-50 and <i>bla</i>_TEM-85.</p

Adaptive landscapes of TEM-85.

<p>These diagrams show the pathways through which the <i>bla</i>_TEM-85 can evolve in a single antibiotic. 1a. (Left) The TEM-85 adaptive landscape in cefotaxime with pathways to TEM-85 indicated. 1b. (Right) The TEM-85 adaptive landscape in ceftazidime with pathways to TEM-85 indicated.</p

The antibiotics used to characterize adaptive landscapes.

<p>While not a comprehensive listing of all β-lactam antibiotics, this set contains many heavily used antibiotics and provides good general coverage of β-lactams.</p

Example of one possible outcome from antibiotic cycling.

<p>These diagrams show that by alternating the antibiotics cefepime, ceftazidime, and cefprozil susceptibility to those antibiotics can be restored in bacterial populations expressing variant alleles present in TEM-50 adaptive landscapes. 2a. (Top left) The TEM-50 adaptive landscape in cefepime. Yellow peaks indicate the adjacent alleles that are important during cefepime selection. 2b. (Top right) The TEM-50 adaptive landscape in ceftazidime. Orange peaks indicate the adjacent alleles that are important during ceftazidime selection. 2c. (Bottom left) The TEM-50 adaptive landscape in cefprozil. Red peaks indicate the adjacent alleles that are important during cefprozil selection. 2d. (Bottom right) Composite cycle: The yellow arrow indicates the direction of selection in the presence of cefepime. The red arrows indicate the direction of selection in the presence of cefprozil. The orange arrow indicates the direction of selection in the presence of ceftazidime. Rotation of these antibiotics results in cyclical renewal of antibiotic susceptibility.</p