Antibiotic assault leads to the competitive release of the resistant lineage when susceptible and resistant cells are competitors but to a mutualistic suppression when they are mutualists.
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Abstract
<p><b>A.</b> We consider four types of metabolic interactions between the resistant (R) and susceptible (S) strains. R and S compete for shared limiting nutrients and release a toxin that harms the other type (interference competition). R and S compete for shared limiting nutrients (exploitation competition). R and S may compete for space as they grow and divide but no direct competition for shared nutrients (non cross-feeding). R and S feed on each other metabolic by-products (cross-feeding). Open arrows represent a positive effect whereas oval arrows represent a negative effect upon the species they are pointing toward. <b>B.</b> For each scenario above, shown is the outcome of ecological interaction after 36h of growth either without (baseline) or with antibiotics. For this, we plot the number of R cells in coculture minus R cells in monoculture (R<sub>co</sub> -R<sub>mono</sub>) and the number of S cells in coculture minus S cells in monoculture (S<sub>co</sub>—S<sub>mono</sub>). When above (below) the 0 dashed line, a strain does better (worse) in coculture than in monoculture. When R and S grow better together than alone, they are mutualists. When they grow worse together than alone, they are competitors. When one type grows better but the other grows worse, the former exploits the latter. <b>C.</b> Shown is the number of R and S cells after 36h of coculture growth. Competitive release of R occurs when <i>R</i><sub>co</sub> [antibiotic>0]—<i>R</i><sub>co</sub> [antibiotic = 0] > 0. Mutualistic suppression occurs when <i>R</i><sub>co</sub> [antibiotic>0]—<i>R</i><sub>co</sub> [antibiotic = 0] <0. Cross-species phenotypic resistance is defined as <i>S</i><sub>co</sub> [antibiotic>0]—<i>S</i><sub>mono</sub> [antibiotic>0] >0 (see <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1006179#pcbi.1006179.s001" target="_blank">S1 Fig</a> for time series). <b>D.</b> The images show examples of simulations at t = 24h. Resistance is cost-free (assumption relaxed later). R and S are randomly seeded at 1:1.</p
