title: Carbon monoxide releasing molecule-2 (CORM-2) inhibits growth of multidrug-resistant uropathogenic Escherichia coli in biofilm and following host cell colonization.
abstract: BACKGROUND
  Increased resistance to antimicrobial agents is a characteristic of many bacteria growing in biofilms on for example indwelling urinary catheters or in intracellular bacterial reservoirs. Biofilm-related infections caused by multidrug-resistant bacteria, such as extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, are a major challenge. The aim of this study was to investigate if a carbon monoxide-releasing molecule (CORM-2) has antibacterial effects against ESBL-producing uropathogenic E. coli (UPEC) in the biofilm mode of growth and following colonization of host bladder epithelial cells.
  
  
  RESULTS
  The effect of CORM-2 was examined on bacteria grown within an established biofilm (biofilm formed for 24 h on plastic surface) by a live/dead viability staining assay. CORM-2 (500 μM) exposure for 24 h killed approximately 60 % of the ESBL-producing UPEC isolate. A non-ESBL-producing UPEC isolate and the E. coli K-12 strain TG1 were also sensitive to CORM-2 exposure when grown in biofilms. The antibacterial effect of CORM-2 on planktonic bacteria was reduced and delayed in the stationary growth phase compared to the exponential growth phase. In human bladder epithelial cell colonization experiments, CORM-2 exposure for 4 h significantly reduced the bacterial counts of an ESBL-producing UPEC isolate.
  
  
  CONCLUSIONS
  This study shows that CORM-2 has antibacterial properties against multidrug-resistant UPEC under biofilm-like conditions and following host cell colonization, which motivate further studies of its therapeutic potential.
authors.affiliation: Faculty of Medicine and Health, Örebro University, SE-701 82, Örebro, Sweden.|iRiSC - Inflammatory Responses and Infection Susceptibility Centre, Örebro University, SE-701 82, Örebro, Sweden.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Sahlberg Bang
authors.affiliation: Faculty of Medicine and Health, Örebro University, SE-701 82, Örebro, Sweden.|iRiSC - Inflammatory Responses and Infection Susceptibility Centre, Örebro University, SE-701 82, Örebro, Sweden.
authors.forename: Robert
authors.initials: R
authors.lastname: Kruse
authors.affiliation: Faculty of Medicine and Health, Örebro University, SE-701 82, Örebro, Sweden.
authors.forename: Kjell
authors.initials: K
authors.lastname: Johansson
authors.affiliation: Faculty of Medicine and Health, Örebro University, SE-701 82, Örebro, Sweden. katarina.persson@oru.se.|iRiSC - Inflammatory Responses and Infection Susceptibility Centre, Örebro University, SE-701 82, Örebro, Sweden. katarina.persson@oru.se.
authors.forename: Katarina
authors.initials: K
authors.lastname: Persson
mesh_terms: D058491:Bacterial Load / Q000187:drug effects; D018441:Biofilms / Q000187:drug effects*; D002460:Cell Line; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects; D004927:Escherichia coli Infections / Q000382:microbiology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D009942:Organometallic Compounds / Q000494:pharmacology*; D001743:Urinary Bladder / Q000166:cytology; D056689:Uropathogenic Escherichia coli / Q000187:drug effects / Q000302:isolation & purification / Q000502:physiology*
chemical_list: D009942:Organometallic Compounds; C447082:tricarbonyldichlororuthenium (II) dimer
keywords: Biofilm; CORM-2; Carbon monoxide releasing molecule; Extended-spectrum β-lactamase; Uropathogenic Escherichia coli