Understanding the acute inflammatory response to Pseudomonas aeruginosa infection: differences between susceptible and multidrug-resistant strains in a mouse peritonitis model.

The increasing emergence of multidrug-resistant (MDR) Pseudomonas aeruginosa strains is associated with the spread of a few international epidemic clones called high-risk clones. The existence of a fitness cost associated with multidrug resistance remains unclear, and little is known about the host inflammatory response in acute P. aeruginosa infections. This study aimed to investigate how the inflammatory response occurs in the most relevant high-risk clones and to compare the process with that recorded in clinical susceptible isolates. Nine P. aeruginosa strains were studied, including the most relevant MDR high-risk clones (ST111, ST175 and ST235) circulating worldwide. The inflammatory response in terms of the release of interleukins in serum was investigated in a mouse peritonitis-sepsis model at three time points (4, 8 and 12 h). TNFα and interleukin-10 (IL-10) levels were significantly higher at all time points in mice inoculated with clinical susceptible strains compared with those inoculated with MDR strains. IL-6 levels were significantly higher in the clinical susceptible strain group at 8 h and 12 h (P = 0.036 and P = 0.007, respectively). Bacterial counts (log CFU/mL) in peritoneal fluid were higher in the clinical susceptible strain group compared with the MDR strain group at 8 h [6.00 (4.30-6.90) vs. 4.46 (3.30-5.34); P = 0.005] and 12 h [7.75 (4.00-7.97) vs. 4.04 (2.58-4.94); P = 0.003]. MDR P. aeruginosa strains elicited a weaker inflammatory response than susceptible strains in an experimental mouse model, suggesting the existence of a fitness cost associated with multidrug resistance.