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Oppenheimer-Shaanan, Y.

Publications and source records attributed to Oppenheimer-Shaanan, Y..

5 recordsLinked to original sources

Kingdom-wide Discovery of Type VI Secretion Effectors via AI Uncovers Three New Bacterial Toxins

The type VI secretion system (T6SS) is a molecular harpoon used by 19% of bacteria to inject toxic proteins into microbial or host cells. Despite its widespread distribution, many T6SS effector (T6Es) genes remain unidentified. Here, we developed an XGBoost classifier integrating 42 genetic and biochemical features to identify novel T6Es. Applying our model to 2,559 T6SS-encoding bacterial genomes revealed 19,958 T6E candidates. We validated our computational predictions and confirmed that three effector candidates, having new 3D structures, demonstrated cytotoxicity to bacteria and yeast, mostly in the bacterial periplasm. For two of these, cognate immunity proteins neutralizing toxicity have been validated. T6EC11, a new peptidoglycan degrading effector, quickly leads to spherical E. coli, with inner membrane separation, and gradual peptidoglycan degradation in a unipolar manner, demonstrating an intriguing moon-like structural phenotype. T6EC12, an effector toxic to bacteria and yeast, carries a conserved zinc-binding motif. Mutations the motif markedly reduced toxicity, suggesting that T6EC12 represents a novel metalloprotease. Our study expands the known T6E repertoire, and provides thousands of T6E predictions in all T6SS-encoding bacteria.

microbiology↗

Plasmids, Prophages and Defense Systems are Depleted from Plant Microbiota Genomes

Plant-associated bacteria significantly impact plant growth and health. Understanding how bacterial genomes adapt to plants can provide insights into their growth promotion and virulence functions. Here, we compared 38,912 bacterial genomes and 6,073 metagenomes to explore the distribution of mobile genetic elements and defense systems in plant-associated bacteria. We reveal a consistent taxon-independent depletion of prophages, plasmids, and defense systems in plant-associated bacteria, particularly in the phyllosphere, compared to other ecosystems. The mobilome depletion suggests the presence of unique ecological constraints or molecular mechanisms exerted by plants to control the bacterial mobilomes independently of the bacterial defense.

bioinformatics↗

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↗

A dynamic rhizosphere interplay between tree roots and soil bacteria under drought

O_LIRoot exudates are thought to play an important role in plant-microbial interactions. In return for nutrition, soil bacteria can increase the bioavailability of soil minerals. However, root exudates typically decrease in situations such as drought, calling into question the efficacy of bacteria-dependent mineral uptake in such stress. C_LIO_LIHere we tested the hypothesis of exudate-driven microbial priming on Cupressus saplings grown in forest soil in custom-made rhizotron boxes. A 1-month imposed drought and concomitant inoculations with Bacillus subtilis and Pseudomonas stutzeri, bacteria species isolated from the forest soil, were applied using factorial design. C_LIO_LIDirect bacteria counts and visualization by confocal microscopy showed that both bacteria associated with Cupressus roots. Interestingly, root exudation rates increased with bacteria under drought. Forty four metabolites in exudates were significantly different in concentration between irrigated and drought trees, including phenolic acid compounds and quinate, that were shown to be used as carbon and nitrogen sources by both bacterial species. Importantly, soil phosphorous bioavailability was maintained only in inoculated trees, mitigating drought-induced decrease in leaf phosphorus and iron. C_LIO_LIOur observations of increased root exudation rate when drought and inoculation regimes were combined, support the idea of root recruitment of beneficial bacteria. C_LI

ecology↗

Bacterial gasdermins reveal an ancient mechanism of cell death

Gasdermin proteins form large membrane pores in human cells that release immune cytokines and induce lytic cell death. Gasdermin pore formation is triggered by caspase-mediated cleavage during inflammasome signaling and is critical for defense against pathogens and cancer. Here we discover gasdermin homologs encoded in bacteria that execute prokaryotic cell death. Structures of bacterial gasdermins reveal a conserved pore-forming domain that is stabilized in the inactive state with a buried lipid modification. We demonstrate that bacterial gasdermins are activated by dedicated caspase-like proteases that catalyze site-specific cleavage and removal of an inhibitory C-terminal peptide. Release of autoinhibition induces the assembly of >200 [A] pores that form a mesh-like structure and disrupt membrane integrity. These results demonstrate that caspase-mediated activation of gasdermins is an ancient form of regulated cell death shared between bacteria and animals.

microbiology↗