Impact of multidrug resistance on the pathogenicity of Pseudomonas aeruginosa: in vitro and in vivo studies

• The relationship between pathogenicity and resistance in Pseudomonas aeruginosa was evaluated.
• An experimental peritonitis/sepsis model in C57BL/6 mice was conducted.
• Mice inoculated with susceptible strains showed higher mortality.
• These results support that multidrug resistance in P. aeruginosa is associated with a fitness cost.

The biological cost of multidrug resistance in Pseudomonas aeruginosa (PA) remains unclear. This study aimed to evaluate the relationship between pathogenicity and the resistance profile of different PA strains, including the most common epidemic high-risk clones. Nine PA strains were studied, including two reference strains, PAO1 and PA14 [both susceptible to all antipseudomonals (multiS)], and seven clinical strains comprising three clinical multiS strains, a non-clonal multidrug-resistant (MDR) strain and the high-risk MDR clones ST111, ST235 and ST175. In vitro studies were performed to investigate growth rate, type III secretion system (TTSS) genotype, cytotoxicity and invasiveness. Additionally, a peritonitis/sepsis model was used in C57BL/6 mice. The in vitro bacterial duplication time was shorter in clinical multiS strains than in MDR-PA (0.42 ± 0.08 h vs. 0.55 ± 0.14 h; P = 0.023). Among the clinical strains, exoU+ genotype was observed only in the epidemic clone ST235. In the animal model, the probability of mortality at 48 h was 70% for clinical multiS strains vs. 7.5% for clinical MDR-PA (P < 0.001, log-rank). The high-risk clone ST235 was the only MDR strain that was able to cause mortality. Bacterial concentrations in peritoneal fluid were higher in mice inoculated with multiS strains compared with MDR-PA [log CFU/mL, 8.95 (IQR 3.42–9.32) vs. 1.98 (IQR 1.08–2.80); P < 0.001]. These data indicate that MDR profiles are associated with a reduction in virulence of PA in a murine model. Further studies are needed to elucidate the clinical implications of these results.