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Danov, A.

Publications and source records attributed to Danov, A..

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Toxinome - The Bacterial Protein Toxin Database

Protein toxins are key molecular weapons in biology that are used to attack neighboring cells. Bacteria use protein toxins to kill or inhibit growth of prokaryotic and eukaryotic cells using various modes of action that target essential cellular components. The toxins are responsible for shaping microbiomes in different habitats, for abortive phage infection, and for severe infectious diseases of animals and plants. Although several toxin databases have been developed, each one is devoted to a specific toxin family and they encompass a relatively small number of toxins. Antimicrobial toxins are often accompanied by antitoxins (or immunity proteins) that neutralize the cognate toxins. Here, we combined toxins and antitoxins from many resources and created Toxinome, a comprehensive and updated bacterial protein toxin database. Toxinome includes a total of 1,483,028 toxins and 491,345 antitoxins encoded in 59,475 bacterial genomes across the tree of life. We identified a depletion of toxin and antitoxin genes in bacteria that dwell in extreme temperatures. We defined 5,161 unique Toxin Islands within phylogenetically diverse bacterial genomes, which are loci dense in toxin and antitoxin genes. By focusing on the unannotated genes within these islands, we characterized a number of these genes as toxins or antitoxins. Finally, we developed an interactive Toxinome website (http://toxinome.pythonanywhere.com) that allows searching and downloading of our database. The Toxinome resource will be useful to the large research community interested in bacterial toxins and can guide toxin discovery and function elucidation, and infectious disease diagnosis and treatment. ImportanceMicrobes use protein toxins as important tools to attack neighboring cells, microbial or eukaryotic, and for self-killing when attacked by viruses. These toxins work by different mechanisms to inhibit cell growth or kill cells. Microbes also use antitoxin proteins to neutralize the toxin activities. Here, we developed a comprehensive database called Toxinome of nearly two million toxin and antitoxins that are encoded in 59,475 bacterial genomes. We described the distribution of bacterial toxins and identified that they are depleted from bacteria that live in hot and cold temperatures. We find 5,161 cases in which toxins and antitoxins are densely clustered in bacterial genomes and termed these areas "Toxin Islands". The Toxinome database is a useful resource for anyone interested in toxin biology and evolution, and it can guide discovery of new toxins.

microbiology↗

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

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.

microbiology↗