title: Multiresistant uropathogenic extended-spectrum β-lactamase (ESBL)-producing Escherichia coli are susceptible to the carbon monoxide releasing molecule-2 (CORM-2).
abstract: Carbon monoxide (CO) releasing molecules (CO-RMs) have been shown to inhibit growth of commensal Escherichia coli (E. coli). In the present study we examined the effect of CORM-2 on uropathogenic E. coli (UPEC) that produces extended-spectrum β-lactamase (ESBL). Viability experiments showed that CORM-2 inhibited the growth of several different ESBL-producing UPEC isolates and that 500 μM CORM-2 had a bactericidal effect within 4 h. The bactericidal effect of CORM-2 was significantly more pronounced than the effect of the antibiotic nitrofurantoin. CORM-2 demonstrated a low level of cytotoxicity in eukaryotic cells (human bladder epithelial cell line 5637) at the concentrations and time-points where the antibacterial effect was obtained. Real-time RT-PCR studies of different virulence genes showed that the expression of capsule group II kpsMT II and serum resistance traT was reduced and that some genes encoding iron acquisition systems were altered by CORM-2. Our results demonstrate that CORM-2 has a fast bactericidal effect against multiresistant ESBL-producing UPEC isolates, and also identify some putative UPEC virulence factors as targets for CORM-2. CO-RMs may be candidate drugs for further studies in the field of finding new therapeutic approaches for treatment of uropathogenic ESBLproducing E. coli.
authors.affiliation: Department of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
authors.forename: Charlotte Sahlberg
authors.initials: CS
authors.lastname: Bang
authors.affiliation: Department of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
authors.forename: Robert
authors.initials: R
authors.lastname: Kruse
authors.affiliation: Department of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
authors.forename: Isak
authors.initials: I
authors.lastname: Demirel
authors.affiliation: Department of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden; Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Onnberg
authors.affiliation: Department of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden; Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Söderquist
authors.affiliation: Department of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden. Electronic address: katarina.persson@oru.se.
authors.forename: Katarina
authors.initials: K
authors.lastname: Persson
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003470:Culture Media / Q000737:chemistry; D004269:DNA, Bacterial / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial; D004847:Epithelial Cells / Q000187:drug effects; D029968:Escherichia coli Proteins / Q000378:metabolism; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism; D050296:Microbial Viability / Q000187:drug effects; D008875:Middle Aged; D009582:Nitrofurantoin / Q000494:pharmacology; D009942:Organometallic Compounds / Q000494:pharmacology*; D001743:Urinary Bladder / Q000166:cytology; D014556:Urine / Q000382:microbiology; D056689:Uropathogenic Escherichia coli / Q000187:drug effects* / Q000201:enzymology; D037521:Virulence Factors / Q000378:metabolism; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D003470:Culture Media; D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D026901:Membrane Transport Proteins; D009942:Organometallic Compounds; C036297:TraT protein, E coli; D037521:Virulence Factors; C447082:tricarbonyldichlororuthenium (II) dimer; C068104:kpsM protein, E coli; C068103:kpsT protein, E coli; D009582:Nitrofurantoin; D001618:beta-Lactamases
keywords: CORM-2; CTX-M; Carbon monoxide; Extended-spectrum β-lactamases; Uropathogenic E. coli