Interplay among Resistance Profiles, High-Risk Clones, and Virulence in the Caenorhabditis elegansPseudomonas aeruginosa Infection Model

Abstract

The increasing prevalence of nosocomial infections produced by multidrug-resistant (MDR) or extensively drug-resistant (XDR) is frequently linked to widespread international strains designated high-risk clones. In this work, we attempted to decipher the interplay between resistance profiles, high-risk clones, and virulence, testing a large ( = 140) collection of well-characterized isolates from different sources (bloodstream infections, nosocomial outbreaks, cystic fibrosis, and the environment) in a infection model. Consistent with previous data, we documented a clear inverse correlation between antimicrobial resistance and virulence in the model. Indeed, the 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 sequence type 111 (ST111) and ST235 but very low for ST175. The highest virulence of ST235 could be attributed to its type III secretion system (TTSS) genotype, which was found to be linked with higher virulence in our model. Other markers, such as motility or pigment production, were not essential for virulence in the model but seemed to be related with the higher values of the statistical normalized data. In contrast to ST235, the ST175 high-risk clone, which is widespread in Spain and France, seems to be associated with a particularly low virulence in the 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 resistance profiles, high-risk clones, and virulence.

ThePseudomonas aeruginosaaccessory genome elements influence virulence towardsCaenorhabditis elegans

“…chosen for this study have undergone selection in the wild through direct interaction with C. elegans. We observed that 62 amongst our 52-strain panel, environmental strain isolates exhibited on average greater virulence against C. elegans than 63 did clinical isolates (Supplemental figure 1B), consistent with previous findings (Sánchez-Diener et al, 2017). This 64…”

A Case-Control Study of Real-Life Experience with Ceftolozane-Tazobactam in Patients with Hematologic Malignancy and Pseudomonas aeruginosa Infection

“…Multidrug-resistant strains were more frequent among the cases. It has been documented that XDR strains show a lower virulence, particularly ST175, which is the XDR clone most frequent in Spain (15). But the association between XDR and mortality is not straight forward, as inappropriate therapy is more common for XDR strains.…”

High prevalence of atypical virulotype and genetically diverse background among Pseudomonas aeruginosa isolates from a referral hospital in the Brazilian Amazon

“…The exoU gene is found less frequently due to its presence being associated to the PAPI-2 in the accessory genome of P. aeruginosa, however, its presence and the secretion of its respective protein are markers of very highly cytotoxic phenotype and associated with several types of acute infections, antimicrobial resistance phenotype, polymicrobial infections and early mortality individuals [18,31,71,72]. Moreover, exoS/exoU genes tend to be mutually exclusive, being observed a higher prevalence of the invasive virulotype (exoS + /exoU -) among P. aeruginosa strains worldwide [16,19,23,59].…”