Resistant Traits in Digital Organisms Do Not Revert Preselection Status despite Extended Deselection: Implications to Microbial Antibiotics Resistance

Antibiotics resistance is a serious biomedical issue as formally susceptible organisms gain resistance under its selective pressure. There have been contradictory results regarding the prevalence of resistance following withdrawal and disuse of the specific antibiotics. Here, we use experimental evolution in "digital organisms" to examine the rate of gain and loss of resistance under the assumption that there is no fitness cost for maintaining resistance. Our results show that selective pressure is likely to result in maximum resistance with respect to the selective pressure. During deselection as a result of disuse of the specific antibiotics, a large initial loss and prolonged stabilization of resistance are observed, but resistance is not lost to the stage of preselection. This suggests that a pool of partial persists organisms persist long after withdrawal of selective pressure at a relatively constant proportion. Hence, contradictory results regarding the prevalence of resistance following withdrawal and disuse of the specific antibiotics may be a statistical variation about constant proportion. Our results also show that subsequent reintroduction of the same selective pressure results in rapid regain of maximal resistance. Thus, our simulation results suggest that complete elimination of specific antibiotics resistance is unlikely after the disuse of antibiotics once a resistant pool of microorganisms has been established.