The Effect of Horizontal Gene Transfer on the Dynamics of Antibiotic Drug Resistance in a Unicellular Population with a Dynamic Fitness Landscape, Repression and De-repression

Antibiotic drug resistance spreads through horizontal gene transfer (HGT) via bacterial conjugation in unicellular populations of bacteria. Consequently, the efficiency of antibiotics is limited and the expected “grace period” of novel antibiotics is typically quite short. One of the mechanisms that allow the accelerated adaptation of bacteria to antibiotics is bacterial conjugation. However, bacterial conjugation is regulated by several biological factors, with one of the most important ones being repression and derepression. In recent work, we have studied the effects that repression and de-repression on the mutation-selection balance of an HGT-enabled bacterial population in a static environment. Two of our main findings were that conjugation has a deleterious effect on the mean fitness of the population and that repression is expected to allow a restoration of the fitness cost due to plasmid hosting. Here, we consider the effect that conjugation-mediated HGT has on the speed of adaptation in a dynamic environment and the effect that repression will have on the dynamics of antibiotic drug resistance. We find that, the effect of repression is dynamic in its possible outcome, that a conjugators to non-conjugators phase transition exists in a dynamic landscape as we have previously found for a static landscape and we quantify the time required for a unicellular population to adapt to a new antibiotic in a periodically changing fitness landscape. Our results also confirmed that HGT accelerates adaptation for a population of prokaryotes which agrees with current knowledge, that HGT rates increase when a population is put under stress.