The effect of cross-feeding on mutant fitness in microbial communities

The distribution of fitness effects (DFE) is key to predicting evolution in microbial populations and a popular readout in microbial ecology. Empirical measurements based on transposon-insertion mutant libraries show that the DFE reshuffles with the presence of additional strains in the environment, sometimes reducing the overall speed of adaptation. However, the mechanisms by which microbial interactions affect the DFE remain unclear. Here we use in-silico fitness assays with genome-scale metabolic models to estimate the effect of nutrient exchange on mutant fitness. We present a pipeline to quantify the speed of invasion for gene knockouts in the community setting, building on the asymmetry of the invasion to disentangle the inference of the community state from the inference of the mutant growth rate. We apply this approach to estimate DFEs for a synthetic community of E.coli auxotrophs that cross-feed essential amino acids. We find that the community provides a lower level of nutrients and this, suprisingly, restores fitness of deleterious gene knockouts. We conceptualize these changes in the DFE across environments in terms of nutrient limitation and take a closer look at metabolic cheaters as another way of rescue. Altogether, these results suggest explicit mechanisms for mutant rescue in the context of microbial communities and demonstrate how simple metabolic models can be used to probe the DFE and its environmental dependence.