Translation initiation or elongation inhibition triggers contrasting effects on Caenorhabditis elegans survival during pathogen infection

Diverse microbial pathogens are known to attenuate host protein synthesis. Consequently, the host mounts a defense response against protein translation inhibition, leading to increased transcript levels of immune genes. The seemingly paradoxical upregulation of immune gene transcripts in response to blocked protein synthesis suggests that the defense mechanism against translation inhibition may not universally benefit host survival. However, a comprehensive assessment of host survival on pathogens upon blockage of different stages of protein synthesis is currently lacking. Here, we investigate the impact of knockdown of various translation initiation and elongation factors on the survival of Caenorhabditis elegans exposed to Pseudomonas aeruginosa . Intriguingly, we observe contrasting effects on C. elegans survival during P. aeruginosa exposure upon inhibition of initiation and elongation factors. While inhibiting both initiation and elongation factors leads to an upregulation of immune gene expression and reduced colonization of the C. elegans gut by P. aeruginosa , inhibiting initiation factors proves beneficial, whereas inhibiting elongation factors proves detrimental to C. elegans survival. We demonstrate that the bZIP transcription factor, ZIP-2, mediates both the advantageous and deleterious effects of inhibiting translation initiation and elongation. Therefore, our findings unveil the opposing roles of translation initiation and elongation in C. elegans survival during P. aeruginosa infection, with the same transcription factor, ZIP-2, orchestrating these opposing effects. ### Competing Interest Statement The authors have declared no competing interest.