Biosynthetic gene cluster profiling predicts the positive association between antagonism and phylogeny in Bacillus

Liming Xia,Ruifu Zhang,A’Li Cao,Qirong Shen,Yansheng Xue,Zhihui Xu,Nan Zhang,Zihao Liu,Weibing Xun,Youzhi Miao,Yan Liu,Xinli Sun

doi:10.1038/s41467-022-28668-z

Abstract

Understanding the driving forces and intrinsic mechanisms of microbial competition is a fundamental question in microbial ecology. Despite the well-established negative correlation between exploitation competition and phylogenetic distance, the process of interference competition that is exemplified by antagonism remains controversial. Here, we studied the genus Bacillus, a commonly recognized producer of multifarious antibiotics, to explore the role of phylogenetic patterns of biosynthetic gene clusters (BGCs) in mediating the relationship between antagonism and phylogeny. Comparative genomic analysis revealed a positive association between BGC distance and phylogenetic distance. Antagonistic tests demonstrated that the inhibition phenotype positively correlated with both phylogenetic and predicted BGC distance, especially for antagonistic strains possessing abundant BGCs. Mutant-based verification showed that the antagonism was dependent on the BGCs that specifically harbored by the antagonistic strain. These findings highlight that BGC-phylogeny coherence regulates the positive correlation between congeneric antagonism and phylogenetic distance, which deepens our understanding of the driving force and intrinsic mechanism of microbial interactions.

Highlights

Understanding the driving forces and intrinsic mechanisms of microbial competition is a fundamental question in microbial ecology
Based on comparative genomic analysis, antagonistic assessments, and mutant-based verification, we show that the distribution profile of Biosynthetic gene clusters (BGCs) within Bacillus genomes is consistent with their phylogenetic relationship; the congeneric antagonism among Bacillus strains positively correlates with phylogenetic distance, and this inhibition is dependent on the BGCs that harbored by the antagonistic strain
Phylogenetic analysis based on the sequences of 120 ubiquitous single-copy proteins[27] showed that the 139 species could be generally clustered into four clades (Fig. 1 and Supplementary Data 2; the phylogenetic tree including all the detailed species information is shown in Supplementary Fig. 1), including a subtilis clade that includes species from diverse niches and can be further divided into the subtilis and pumilus subclades, a cereus clade that contains typical pathogenic species (B. cereus, B. anthracis, B. thuringiensis, etc.), a megaterium clade, and a circulans clade

Summary

Introduction

Understanding the driving forces and intrinsic mechanisms of microbial competition is a fundamental question in microbial ecology. Antagonistic tests demonstrated that the inhibition phenotype positively correlated with both phylogenetic and predicted BGC distance, especially for antagonistic strains possessing abundant BGCs. Mutantbased verification showed that the antagonism was dependent on the BGCs that harbored by the antagonistic strain. Mutantbased verification showed that the antagonism was dependent on the BGCs that harbored by the antagonistic strain These findings highlight that BGC-phylogeny coherence regulates the positive correlation between congeneric antagonism and phylogenetic distance, which deepens our understanding of the driving force and intrinsic mechanism of microbial interactions. The relationship between antagonism and phylogenetic distance with regard to microbes from different taxonomical scales or groups, as well as the involved biological mechanism, is still under debate, which limits both our understanding and application of these microbial interactions. We hypothesize that the correlation between BGC and phylogenetic distance can predict the pattern of congeneric antagonism among different taxonomic groups, as strains possessing higher

Methods

Results

Conclusion