Emergence of Novel Pathogenic Streptomyces Species by Site-Specific Accretion and cis-Mobilization of Pathogenicity Islands

Abstract

The main pathogenicity factor of Streptomyces species associated with the potato common scab disease is a nitrated diketopiperazine called thaxtomin A (ThxA). In Streptomyces scabiei (syn. S. scabies), which is thought to be the most ancient pathogenic Streptomyces species, the ThxA biosynthetic cluster is located within a mobile genomic island called the toxicogenic region (TR). Three attachment (att) sites further separate TR into two subregions (TR1 and TR2). TR1 contains the ThxA biosynthetic cluster and is conserved among several pathogenic Streptomyces species. However, TR2, an integrative and conjugative element, is missing in most pathogenic species. In our previous study, we demonstrated the mobilization of the whole TR element or TR2 alone between S. scabiei and nonpathogenic Streptomyces species. TR1 alone did not mobilize in these experiments. These data suggest that TR2 is required for the mobilization of TR1. Here, we show that TR2 can self mobilize to pathogenic Streptomyces species harboring only TR1 and integrate into the att site of TR1, leading to the tandem accretion of resident TR1 and incoming TR2. The incoming TR2 can further mobilize resident TR1 in cis and transfer to a new recipient cell. Our study demonstrated that TR1 is a nonautonomous cis-mobilizable element and that it can hijack TR2 recombination and conjugation machinery to excise, transfer, and integrate, leading to the dissemination of pathogenicity genes and emergence of novel pathogenic species. Additionally, comparative genomic analysis of 23 pathogenic Streptomyces isolates from ten species revealed that the composite pathogenicity island (PAI) formed by TR1 and TR2 is dynamic and various compositions of the island exist within the population of newly emerged pathogenic species, indicating the structural instability of this composite PAI.