Antagonism correlates with metabolic similarity in diverse bacteria

Abstract

In the Origin of Species, Charles R. Darwin [Darwin C (1859) On the Origin of Species] proposed that the struggle for existence must be most intense among closely related species by means of their functional similarity. It has been hypothesized that this similarity, which results in resource competition, is the driver of the evolution of antagonism among bacteria. Consequently, antagonism should mostly be prevalent among phylogenetically and metabolically similar species. We tested the hypothesis by screening for antagonism among all possible pairwise interactions between 67 bacterial species from 8 different environments: 2,211 pairs of species and 4,422 interactions. We found a clear association between antagonism and phylogenetic distance, antagonism being most likely among closely related species. We determined two metabolic distances between our strains: one by scoring their growth on various natural carbon sources and the other by creating metabolic networks of predicted genomes. For both metabolic distances, we found that the probability of antagonism increased the more metabolically similar the strains were. Moreover, our results were not compounded by whether the antagonism was between sympatric or allopatric strains. Intriguingly, for each interaction the antagonizing strain was more likely to have a wider metabolic niche than the antagonized strain: that is, larger metabolic networks and growth on more carbon sources. This indicates an association between an antagonistic and a generalist strategy.

Keywords: antagonism; antibiotics; bacteria; competition; competition-relatedness hypothesis.

Fig. 1.

(A) Bacteria mainly antagonize closely related genotypes; the probability of inhibition increases with decreasing 16S rRNA gene phylogenetic distance. The red line is a logistic regression and the gray shaded area denotes the 95% confidence interval. (P < 0.001, n = 2,211). (B) Few strains inhibit many others, but these superkillers are randomly distributed across the phylogeny.

Fig. S1.

Heatmap of all interactions ordered by the phylogenetic tree. Antagonistic interactions are shown in blue.

Fig. 2.

(A) A functional distance was calculated between all strain pairs by overlapping the compounds (nodes) in their metabolic networks. (B) The probability of inhibition increases with decreasing functional distance. The red line is a logistic regression and the gray shaded area denotes the 95% confidence intervals (P < 0.001, n = 2,211). (C) The probability of inhibition increases with decreasing metabolic distance as calculated from their growth patterns on BiOLOG Ecoplates. The red line is a logistic regression and the gray shaded area denotes the 95% confidence intervals (P = 0.0023, n = 1,770).

Fig. S2.

(A) Correlation between functional distance and phylogenetic distance. The red line is a linear regression. (B) Correlation between metabolic distance and phylogenetic distance. The red line is a linear regression.

Fig. 3.

(A) The ratios between metabolic network sizes of the antagonists compared with the antagonized are larger than 1 when antagonism was observed (P = 0), but not different from 1 for the remaining interactions (P = 0.99). (B) The log₂ ratios between the number of carbon sources antagonists grow on compared with how many the antagonized grow on are larger than 0 when antagonism was observed (P = 0.03), but not different from 0 for the remaining interactions (P = 1). P values are one-tailed tests of whether medians are larger than 1 (A) or 0 (B) estimated from 1,000 bootstrap realizations. Points are medians and error bars are 90% bootstrapped confidence limits of the medians (equivalent to 5% one-tailed test of the median). (n = 148 and n = 4,274 for “antagonism” and “no antagonism,” respectively).

Fig. 4.

(A) The proportion of inhibitory interactions is no different whether the strains were sympatric or allopatric (OR = 0.97, P = 0.90, Fisher’s exact test). (B and C) There is no difference in the distribution of phylogenetic or functional distances between sympatric and allopatric strains, but there is an overrepresentation of sympatric strains that are (D) metabolically similar.