Simulating multi-level dynamics of antimicrobial resistance in a membrane computing model

Abstract

Membrane Computing is a bio-inspired computing paradigm, whose devices are the socalled membrane systems or P systems. The P system designed in this work reproduces complex biological landscapes in the computer world. It uses nested "membranesurrounded entities" able to divide, propagate and die, be transferred into other membranes, exchange informative material according to flexible rules, mutate and being 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 multi-level evolutionary biology of antibiotic resistance. We examine a number of selected landscapes where we predict the effects of different rates of patient flow from hospital to the community and viceversa, crosstransmission rates between patients with bacterial propagules of different sizes, the proportion of patients treated with antibiotics, antibiotics and dosing in opening spaces in the microbiota where resistant phenotypes multiply. We can also evaluate the selective strength 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 multi-level analysis of complex microbial landscapes.

Allogenous Selection of Mutational Collateral Resistance: Old Drugs Select for New Resistances Within Antibiotic Families

“…That difference suggests to us and others (Karen Bush, personal communication) that aminopenicillins might be sufficiently hydrolyzed by ESBLs to select for ESBL-containing organisms. However, most ESBL-containing organisms retain early aminopenicillin-hydrolyzing TEM or SHV enzymes even in the presence of ESBLs, which probably minimizes specific selection of ESBL-only strains, as has been indicated by membrane-computational models (Campos et al, 2019). In any case, the frequent coexistence of genes encoding early TEM-1 or SHV-1 beta-lactamases with ESBLs ensures that strains with ESBLs are also selected with aminopenicillins or first-generation cephalosporins.…”