title: Understanding the acute inflammatory response to Pseudomonas aeruginosa infection: differences between susceptible and multidrug-resistant strains in a mouse peritonitis model.
abstract: 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.
authors.affiliation: Infectious Diseases Service, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), University of Barcelona, Feixa Llarga s/n 08907, Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Gómez-Zorrilla
authors.affiliation: Microbiology Service, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), University of Barcelona, Feixa Llarga s/n 08907, Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Calatayud
authors.affiliation: Microbiology Service, Hospital Universitario Son Espases, Instituto de Investigación Sanitaria de Palma (IdiSPa), Ctra. Valldemossa 79, 07010 Palma de Mallorca, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Juan
authors.affiliation: Microbiology Service, Hospital Universitario Son Espases, Instituto de Investigación Sanitaria de Palma (IdiSPa), Ctra. Valldemossa 79, 07010 Palma de Mallorca, Spain.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Cabot
authors.affiliation: Microbiology Service, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), University of Barcelona, Feixa Llarga s/n 08907, Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Fe
authors.initials: F
authors.lastname: Tubau
authors.affiliation: Microbiology Service, Hospital Universitario Son Espases, Instituto de Investigación Sanitaria de Palma (IdiSPa), Ctra. Valldemossa 79, 07010 Palma de Mallorca, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Oliver
authors.affiliation: Microbiology Service, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), University of Barcelona, Feixa Llarga s/n 08907, Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Maria Angeles
authors.initials: MA
authors.lastname: Dominguez
authors.affiliation: Infectious Diseases Service, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), University of Barcelona, Feixa Llarga s/n 08907, Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Ariza
authors.affiliation: Infectious Diseases Service, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), University of Barcelona, Feixa Llarga s/n 08907, Hospitalet de Llobregat, Barcelona, Spain. Electronic address: cpena@bellvitgehospital.cat.
authors.forename: Carmen
authors.initials: C
authors.lastname: Peña
mesh_terms: D000818:Animals; D001202:Ascitic Fluid / Q000382:microbiology; D058491:Bacterial Load; D004195:Disease Models, Animal; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D007378:Interleukins / Q000097:blood; D008810:Mice, Inbred C57BL; D010538:Peritonitis / Q000382:microbiology* / Q000473:pathology*; D011552:Pseudomonas Infections / Q000382:microbiology* / Q000473:pathology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D044967:Serum / Q000737:chemistry; D018746:Systemic Inflammatory Response Syndrome / Q000473:pathology*
chemical_list: D007378:Interleukins
keywords: Animal model; Antibiotic resistance; High-risk clone; Interleukin-10; Interleukin-6; Tumour necrosis factor-alpha