Simulating Multilevel Dynamics of Antimicrobial Resistance in a Membrane Computing Model

Abstract

[EN] Membrane computing is a bio-inspired computing paradigm whose devices are the so-called membrane systems or P systems. The P system designed in this work reproduces complex biological landscapes in the computer world. It uses nested "membrane-surrounded entities" able to divide, propagate, and die; to be transferred into other membranes; to exchange informative material according to flexible rules; and to mutate and be selected by external agents. This allows the exploration of hierarchical interactive dynamics resulting from the probabilistic interaction of genes (phenotypes), clones, species, hosts, environments, and antibiotic challenges. Our model facilitates analysis of several aspects of the rules that govern the multilevel evolutionary biology of antibiotic resistance. We examined a number of selected landscapes where we predict the effects of different rates of patient flow from hospital to the community and vice versa, the cross-transmission rates between patients with bacterial propagules of different sizes, the proportion of patients treated with antibiotics, and the antibiotics and dosing found in the opening spaces in the microbiota where resistant phenotypes multiply. We also evaluated the selective strengths of some drugs and the influence of the time 0 resistance composition of the species and bacterial clones in the evolution of resistance phenotypes. In summary, we provide case studies analyzing the hierarchical dynamics of antibiotic resistance using a novel computing model with reciprocity within and between levels of biological organization, a type of approach that may be expanded in the multilevel analysis of complex microbial landscapes.