title: Impact of multidrug resistance on the pathogenicity of Pseudomonas aeruginosa: in vitro and in vivo studies.
abstract: 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±0.08h vs. 0.55±0.14h; 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 48h 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.
authors.affiliation: Infectious Diseases Service, Hospital Universitari de Bellvitge, Bellvitge Biomedical Research Institute (IDIBELL), University of Barcelona, Feixa Llarga s/n 08907, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Gómez-Zorrilla
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, IDIBELL, University of Barcelona, Feixa Llarga s/n 08907, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Mariana
authors.initials: M
authors.lastname: Camoez
authors.affiliation: Microbiology Service, Hospital Universitari de Bellvitge, IDIBELL, University of Barcelona, Feixa Llarga s/n 08907, L'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, IDIBELL, University of Barcelona, Feixa Llarga s/n 08907, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: M 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, L'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, L'Hospitalet de Llobregat, Barcelona, Spain. Electronic address: cpena@bellvitgehospital.cat.
authors.forename: Carmen
authors.initials: C
authors.lastname: Peña
mesh_terms: D000818:Animals; D058491:Bacterial Load; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D024901:Drug Resistance, Multiple, Bacterial; D004705:Endocytosis; D005260:Female; D008810:Mice, Inbred C57BL; D010538:Peritonitis / Q000382:microbiology / Q000473:pathology; D011552:Pseudomonas Infections / Q000382:microbiology / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism / Q000472:pathogenicity*; D018805:Sepsis / Q000382:microbiology / Q000473:pathology; D016019:Survival Analysis; D000069296:Type III Secretion Systems / Q000378:metabolism; D014774:Virulence
chemical_list: D000069296:Type III Secretion Systems
keywords: Animal models; Antibiotic resistance; Biological cost; Epidemic clones; High-risk clones; Pseudomonas aeruginosa