Figure 1. Experimental and biological features of effective drug sequences.

(A) Batra et al. applied different sequences of antibiotics to 756 populations of P. aeruginosa (top panel). The bacteria were treated with either a single drug (monotherapy; row 1), or three antibiotics which were switched rapidly (row 2), slowly (row 3) or in a random order (row 4): the three drugs were either from the same class (homogeneous) or from different classes (heterogeneous). This experiment revealed that fast (blue line) and random (green line) switching between three homogeneous beta-lactam drugs reduced bacteria growth and resulted in higher levels of extinction (bottom graph). (B) The effects of the different sequences are also impacted by biological features. (Top panel) When sensitive bacteria (shown in purple) are treated with the first drug, some cells will evolve genetic changes that make them resistant to the antibiotic treatment (shown in green). These evolutionary changes can lead to collateral effects that make the bacteria less (top arrow), equally (middle arrow) or more (bottom arrow) resistant to the second drug. (Bottom panel) Treatment with the first drug may also lead to negative hysteresis, when short-term physiological changes enhance the bacteria’s response to the second drug (right), leading to more cell death in the population compared to bacteria not pre-treated with the first drug (left).

Image credit: Anh Huynh.