Abstract
Pathogens such as Pseudomonas aeruginosa advantageously modify animal host physiology, for example, by inhibiting host protein synthesis. Translational inhibition of insects and mammalian hosts by P. aeruginosa utilizes the well-known exotoxin A effector. However, for the infection of Caenorhabditis elegans by P. aeruginosa, the precise pathways and mechanism(s) of translational inhibition are not well understood. We found that upon exposure to P. aeruginosa PA14, C. elegans undergoes a rapid loss of intact ribosomes accompanied by the accumulation of ribosomes cleaved at helix 69 (H69) of the 26S ribosomal RNA (rRNA), a key part of ribosome decoding center. H69 cleavage is elicited by certain virulent P. aeruginosa isolates in a quorum sensing (QS)-dependent manner and independently of exotoxin A-mediated translational repression. H69 cleavage is antagonized by the 3 major host defense pathways defined by the pmk-1, fshr-1, and zip-2 genes. The level of H69 cleavage increases with the bacterial exposure time, and it is predominantly localized in the worm's intestinal tissue. Genetic and genomic analysis suggests that H69 cleavage leads to the activation of the worm's zip-2-mediated defense response pathway, consistent with translational inhibition. Taken together, our observations suggest that P. aeruginosa deploys a virulence mechanism to induce ribosome degradation and H69 cleavage of host ribosomes. In this manner, P. aeruginosa would impair host translation and block antibacterial responses.
Highlights
Pathogens deploy diverse virulence mechanisms to exploit host resources and to counteract or evade host defenses
In order to study the effect of exposure to P. aeruginosa strain PA14 on the worm ribosomes, we analyzed by capillary electrophoresis the total RNA profile of adult hermaphrodites fed either with E. coli or with P. aeruginosa strain PA14
Total RNA extracted from adults after 24 h on PA14-seeded slow killing (SK) plates exhibited 2 prominent RNA bands of Pseudomonas aeruginosa induces helix 69 (H69) cleavage approximately 1,100 nucleotides and 2,300 nt (Fig 1A) that were not observed in the control condition of worms feed with E. coli HB101
Summary
Pathogens deploy diverse virulence mechanisms to exploit host resources and to counteract or evade host defenses. The host translational machinery, including the ribosome and associated factors, is frequently targeted in such host–pathogen interactions [1]. Pathogenic bacteria benefit from repression of host protein synthesis, through accelerated cellular damage and blockage of host immune responses. Instances of host translation targeting by pathogenic bacteria include those elicited by Corynebacterium diphtheriae, Vibrio cholerae, and Pseudomonas aeruginosa, which encode bacterial toxins that ADP-ribosylate and inhibit the eukaryotic translation elongation factor 2 [2,3].
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