Interplay among resistance profiles, high-risk clones and virulence in the Caenorhabditis elegans Pseudomonas aeruginosa infection model [PublishAheadOfPrint]

The increasing prevalence of nosocomial infections produced by multidrug-resistant (MDR) or extensively drug-resistant (XDR) Pseudomonas aeruginosa is frequently linked to widespread international strains designated as high-risk clones. In this work we attempted to decipher the interplay between resistance profiles, high-risk clones and virulence, testing a large (n=140) collection of well characterized P. aeruginosa isolates from different sources (bloodstream infections, nosocomial outbreaks, cystic fibrosis and environment) in a Caenorhabditis elegans infection model. Consistently with previous data, we documented a clear inverse correlation between antimicrobial resistance and virulence in the C. elegans model. Indeed, lowest virulence was linked to XDR profiles, which were typically linked to defined high-risk clones. However, virulence varied broadly depending on the involved high-risk clone; it was high for ST111 and ST235 but very low for ST175. The highest virulence of ST235 could be attributed to its ExoU+ Type III secretion system (TTSS) genotype, found to be linked with higher virulence in our C. elegans model. Other markers, such as motility or pigment production were not essential for virulence in the C. elegans model, but seemed to be related with the higher values of the statistical normalized data. Opposite to ST235, the ST175 high-risk clone, widespread in Spain and France, seems to be associated with a particularly low virulence in the C. elegans model. Moreover, the previously described G154R AmpR mutation, prevalent in ST175, was found to contribute to the reduced virulence, although it was not the only factor involved. Altogether, our results provide a major step forward for understanding the interplay between P. aeruginosa resistance profiles, high-risk clones and virulence.

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