PT - JOURNAL ARTICLE AU - Samir Giri AU - Leonardo Oña AU - Silvio Waschina AU - Shraddha Shitut AU - Ghada Yousif AU - Christoph Kaleta AU - Christian Kost TI - Metabolic dissimilarity determines the establishment of cross-feeding interactions in bacteria AID - 10.1101/2020.10.09.333336 DP - 2021 Jan 01 TA - bioRxiv PG - 2020.10.09.333336 4099 - http://biorxiv.org/content/early/2021/03/05/2020.10.09.333336.short 4100 - http://biorxiv.org/content/early/2021/03/05/2020.10.09.333336.full AB - The exchange of metabolites among different bacterial genotypes profoundly impacts the structure and function of microbial communities. However, the factors governing the establishment of these cross-feeding interactions remain poorly understood. While shared physiological features may facilitate interactions among more closely related individuals, a lower relatedness should reduce competition and thus increase the potential for synergistic interactions. Here we investigate how the relationship between a metabolite donor and recipient affects the propensity of strains to engage in unidirectional cross-feeding interactions. For this, we performed pairwise cocultivation experiments between four auxotrophic recipients and 25 species of potential amino acid donors. Auxotrophic recipients grew in the vast majority of pairs tested (78%), suggesting metabolic cross-feeding interactions are readily established. Strikingly, both the phylogenetic distance between donor and recipient and the dissimilarity of their metabolic networks were positively associated with the growth of auxotrophic recipients. Analysing the co-growth of species from a gut microbial community in-silico also revealed that recipient genotypes benefitted more from interacting with metabolically dissimilar partners, thus corroborating the empirical results. Together, our work identifies the metabolic dissimilarity between bacterial genotypes as key factor determining the establishment of metabolic cross-feeding interactions in microbial communities.HighlightsThe exchange of essential metabolites is common in microbial communitiesMetabolic cross-feeding interactions readily establish between auxotrophic and prototrophic bacterial strainsBoth the phylogenetic and the metabolic dissimilarity between donors and recipients determines the successful establishment of metabolic cross-feeding interactionsCompeting Interest StatementThe authors have declared no competing interest.