An interesting manuscript in bioRxiv describes the computational analysis of fitness peaks in characterised drug-resistant bacteria to iterate the importance of ‘mixed drugs’ treatments. The use of more than one antibiotic is an already established practice as it allows to: i) kill a wider spectrum of microbes by targeting different biological processes and, in a more advance approach, ii) decrease the likelihood of the appearance of drug-resistance mutations in individual proteins.
The Authors of this manuscript offer a third reason for this procedure: a single drug might lead to a very ‘specialised’ response at molecular level that could result in an evolutionary bottleneck, i.e. the protein is unable (less likely) to further evolve to cope with a second drug. So, in addition to choosing a pair of effective drugs, the timing of their use also becomes critical.
A computational analysis that, in the words of the authors, ‘in the absence of experimentally determined landscapes‘ cannot answer all concerns about the validity of this approach, but a intriguing and valid perspective on the development of (multi) drug-resistant bacteria nevertheless.