Govindan, J. A. | Search bioRxiv

bioRxiv2020

Bacterial carotenoids suppress Caenorhabditis elegans surveillance and defense of translational dysfunction

Microbial toxins and virulence factors often target the eukaryotic translation machinery. Caenorhabditis elegans surveils for such microbial attacks by monitoring translational competence, and if a deficit is detected, particular drug detoxification and bacterial defense genes are induced. The bacteria Kocuria rhizophila has evolved countermeasures to animal translational surveillance and defense pathways. Here, we used comprehensive genetic analysis of Kocuria rhizophila to identify the bacterial genetic pathways that inhibit C. elegans translational toxin surveillance and defense. Kocuria rhizophila mutations that disrupt its ability to disable animal immunity and defense map to multiple steps in the biosynthesis of a 50-carbon bacterial carotenoid from 5 carbon precursors. Extracts of the C50 carotenoid from wild type K. rhizophila could restore this bacterial anti-immunity activity to K. rhizophila carotenoid biosynthetic mutant. Corynebacterium glutamicum, also inhibits the C. elegans translation detoxification response by producing the C50 carotenoid decaprenoxanthin, and C. glutamicum carotenoid mutants are defective in this suppression of C. elegans detoxification. Consistent with the salience of these bacterial countermeasures to animal drug responses, bacterial carotenoids sensitize C. elegans to drugs that target translation and inhibit food aversion behaviors normally induced by protein translation toxins or mutations. The surveillance and response to toxins is mediated by signaling pathways conserved across animal phylogeny, suggesting that these bacterial carotenoids may also suppress such human immune and toxin responses.

genomics↗

bioRxiv2019

Interkingdom competition for Fe(III) revealed by a synthetic lethal interaction between Caenorhabditis elegans mitochondrial electron transport and Escherichia coli siderophore iron release mutations

C. elegans consumes bacteria which can supply essential vitamins and cofactors especially for mitochondrial functions ancestrally related to bacteria. Therefore, we screened the Keio E. coli knockout library for mutations that induce a C. elegans mitochondrial damage response gene. We identified 45 E. coli mutations that induce a the C. elegans hsp-6::gfp response gene. Surprisingly, four of these E. coli mutations that disrupt the import or removal of iron from the bacterial siderophore enterobactin were lethal in combination with C. elegans mutations that disrupt particular iron-sulfur proteins of the electron transport chain. Bacterial mutations that fail to synthesize enterobactin are not synthetic lethal with these C. elegans mitochondrial mutants; it is the enterobactin-iron complex that is lethal in combination with the C. elegans mitochondrial mutations. Antioxidants suppress this inviability, suggesting that reactive oxygen species (ROS) are produced by the mutant mitochondria in combination with the bacterial enterobactin-iron complex.\n\nSignificance StatementThe animal mitochondrion has a bacterial origin and continues to have a dialogue with the bacterial metabolisms of their microbiome. We identified 45 E. coli gene disruptions that induce a C. elegans mitochondrial damage response gene. Four of these E. coli mutations that disrupt the import or retrieval of iron from the siderophore enterobactin were synthetic lethal with C. elegans mitochondrial mutants. Antioxidants strongly suppressed the inviability of C. elegans mitochondrial mutants grown on the E. coli enterobactin siderophore utilization or import mutants. We hypothesize that reactive oxygen species are produced by C. elegans mitochondrial mutations and that this non-lethal ROS triggers ferric-chelated enterobactin to induce dramatically increased ROS, which leads to lethality.

genetics↗