Pseudomonas aeruginosa killing of Caenorhabditis elegans used to identify P. aeruginosa virulence factors

Abstract

We reported recently that the human opportunistic pathogen Pseudomonas aeruginosa strain PA14 kills Caenorhabditis elegans and that many P. aeruginosa virulence factors (genes) required for maximum virulence in mouse pathogenicity are also required for maximum killing of C. elegans. Here we report that among eight P. aeruginosa PA14 TnphoA mutants isolated that exhibited reduced killing of C. elegans, at least five also exhibited reduced virulence in mice. Three of the TnphoA mutants corresponded to the known virulence-related genes lasR, gacA, and lemA. Three of the mutants corresponded to known genes (aefA from Escherichia coli, pstP from Azotobacter vinelandii, and mtrR from Neisseria gonorrhoeae) that had not been shown previously to play a role in pathogenesis, and two of the mutants contained TnphoA inserted into novel sequences. These data indicate that the killing of C. elegans by P. aeruginosa can be exploited to identify novel P. aeruginosa virulence factors important for mammalian pathogenesis.

Caenorhabditis elegans mom-4 is required for the activation of the p38 MAPK signaling pathway in the response to Pseudomonas aeruginosa infection

“…Slow killing P. aeruginosa assays were performed using the P. aeruginosa strain as described (Tan et al, 1999). All assays performed using L4 or young adult stage hermaphrodites, unless noted.…”

Exploiting Quorum Sensing To Confuse Bacterial Pathogens

“…It has become apparent, however, that this is not always the case. For example, P. aeruginosa QS systems have been demonstrated to be important for pathogenesis in multiple animal infection models (325)(326)(327)(328), and AHLs and QS-regulated genes have been demonstrated to be expressed in vivo (329)(330)(331). However, analyses of clinical P. aeruginosa isolates have revealed that lasR, and less frequently rhlR, can be mutated during infection (332)(333)(334)(335)(336).…”

Pseudomonas aeruginosa las and rhl quorum-sensing systems are important for infection and inflammation in a rat prostatitis model

“…aeruginosa virulence has been shown in numerous model systems. These include the Caenorhabditis elegans model (Tan et al, 1999), the acute pneumonia model (Pearson et al, 2000), and the chronic pneumonia agar bead model (Wu et al, 2001). Since the absence of quorum sensing reduced virulence in all models, including the lung model, we believed that quorum sensing may likewise affect the severity of prostate disease.…”