The extracellular contractile injection system is enriched in environmental microbes and associates with numerous toxins

Abstract

Bacteria employ toxin delivery systems to exclude bacterial competitors and to infect host cells. Characterization of these systems and the toxins they secrete is important for understanding microbial interactions and virulence in different ecosystems. The extracellular Contractile Injection System (eCIS) is a toxin delivery particle that evolved from a bacteriophage tail. Four known eCIS systems have been shown to mediate interactions between bacteria and their invertebrate hosts, but the broad ecological function of these systems remains unknown. Here, we identify eCIS loci in 1,249 prokaryotic genomes and reveal a striking enrichment of these loci in environmental microbes and absence from mammalian pathogens. We uncovered 13 toxin genes that associate with eCIS from diverse microbes and show that they can inhibit growth of bacteria, yeast or both. We also found immunity genes that protect bacteria from self-intoxication, supporting an antibacterial role for eCIS. Furthermore, we identified multiple new eCIS core genes including a conserved eCIS transcriptional regulator. Finally, we present our data through eCIStem; an extensive eCIS repository. Our findings define eCIS as a widespread environmental prokaryotic toxin delivery system that likely mediates antagonistic interactions with eukaryotes and prokaryotes. Future understanding of eCIS functions can be leveraged for the development of new biological control systems, antimicrobials, and cell-free protein delivery tools.

Large-scale discovery of candidate type VI secretion effectors with antibacterial activity

“…Here, we saw the T6SS-encoding genomes are the opposite, with enriched isolation from humans, as well as enriched in a pathogenic lifestyle. Overall, our analysis fits well with previous knowledge about eCIS and T6SS(Alexander Martin Geller et al 2021; L. Chen et al 2019).…”

“…We saw the genera that encoded eCIS and for T6SS were largely non-overlapping, yet we saw exceptions. Dickeya and Xenorhabdus genomes are statistically enriched in both eCIS and T6SS, and Shigella genomes are statistically depleted in both eCIS and T6SS (Figure2) (Alexander MartinGeller et al 2021; L. Chen et al 2019). eCIS-encoding bacteria are mostly found in terrestrial and aquatic environments, and are statistically underrepresented in human isolates, and specifically in human pathogens (A. M Geller et al 2020;Alexander Martin Geller et al 2021)…”

“…is enriched in understudied bacterial genera(Alexander Martin Geller et al 2021; L. Chen et al 2019). eCIS is structurally and evolutionarily related to the T6SS, with the first being extracellular and the second being membrane-bound.…”