Translation initiation or elongation inhibition triggers contrasting effects onCaenorhabditis eleganssurvival during pathogen infection

Abstract

AbstractDiverse 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 ofCaenorhabditis elegansexposed toPseudomonas aeruginosa. Intriguingly, we observe contrasting effects onC. eleganssurvival duringP. aeruginosaexposure 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 theC. elegansgut byP. aeruginosa, inhibiting initiation factors proves beneficial, whereas inhibiting elongation factors proves detrimental toC. eleganssurvival. 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 inC. eleganssurvival duringP. aeruginosainfection, with the same transcription factor, ZIP-2, orchestrating these opposing effects.