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Akerman-Arad, A.

Publications and source records attributed to Akerman-Arad, A..

3 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↗

Conserved inhibitory mechanisms of root-associated bacteria towardsArabidopsis thaliana and Chlamydomonas reinhardtii

Soil bacteria colonize plants without causing visible disease, yet many suppress host growth. The prevalence and evolutionary reach of this cryptic inhibition are unknown, because phenotyping hundreds of isolates in plants is prohibitively slow. Here we use the unicellular algae Chlamydomonas reinhardtii as a scalable proxy for the green lineage. We screened 148 plant-associated bacteria on Chlamydomonas lawns. Seven of eight Chlamydomonas inhibitors also inhibited the vascular model plant Arabidopsis thaliana. In one of these dual inhibitors, Burkholderia sola MF6, transposon screening and proteomics implicated type VI secretion and tight-adherence pili, and over half the non-inhibitory mutants also failed against Arabidopsis. In the algae, infection triggers rapid deflagellation, then non-lytic regulated cell death. The algal zinc/iron transporter ZIP3 promotes inhibition, whereas the cathepsin X protease CEP12 restrains it, and ZIP3 is epistatic to CEP12. Cryptic inhibition is thus ancient and widespread, and a unicellular algae uncovers it at scale.

plant biology↗

The Genetic Basis of Bacterial Adaptation to Hosts

Microbes colonize and interact with diverse multicellular hosts using specialized genes, many of which remain unidentified. Better understanding of host-associated gene functions is a key aspect of microbial ecology. We utilized a large-scale comparative genomics approach to identify and characterize host-associated functions by comparing 72,079 high-quality bacterial genomes from host and non-host environments using five enrichment tests for high accuracy. We uncovered over 3,000 protein domains, 16,000 AlphaFold protein clusters, and 1,500 operons enriched in host-associated bacteria. Additionally, we identified proteins and domains that are enriched in animal- or plant-associated bacteria. These include new functions such as mercury detoxification in hosts and animals in particular, and numerous proteins and domains of unknown function. We validated our results by genetically disrupting five poorly annotated host-associated genes in plant-associated bacteria, resulting in a substantial reduction in rice root colonization. One of the new colonization factors strongly affected bacterial motility and resistance of oxidative stress. Our findings, presented in a new database, GOTHAM DB, reveal the genetic basis of bacterial host association, including new functions underlying host-microbe interactions, and advance our understanding of microbial evolution.

microbiology↗