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Dotan, N.

Publications and source records attributed to Dotan, N..

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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↗

Systematic Discovery of Antimicrobial Polymorphic Toxins

Microbes employ toxins to kill competing microbes or eukaryotic host cells. Polymorphic toxins are proteins that encode C-terminal toxin domains. Here, we developed a computational approach to discover novel toxin domains of polymorphic toxins within 105,438 microbial genomes. We validated nine short novel toxins ("PTs") that cause bacterial or yeast cell death. The novel PTs are encoded by [~]2.2% of the sequenced bacteria, including numerous pathogens. We also identified five cognate immunity genes ("PIMs") that neutralize the toxins. Intriguingly, we observed an antifungal effect of the PTs against various pathogenic fungi. The toxins likely act as enzymes that cause severe damage to cell shape, membrane, and DNA. Finally, we solved the 3D structure of two PTs in complex with their PIMs, and showed that they function as novel DNAses. The new potent toxins likely play key roles in inter-microbial competition and can be utilized in various clinical and biotechnological applications.

microbiology↗