Carbon monoxide releasing molecule-2 (CORM-2) inhibits growth of multidrug-resistant uropathogenic Escherichia coli in biofilm and following host cell colonization

Abstract

BackgroundIncreased 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.ResultsThe 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.ConclusionThis 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.

Emerging Delivery Strategies of Carbon Monoxide for Therapeutic Applications: from CO Gas to CO Releasing Nanomaterials

“…Recently, Gandra et al constructed a stable Mn(I) tricarbonyl complex with turn‐on fluorescence response upon release of CO, which has been utilized to track and confirm CO delivery in cellular matrices. Overall, the controlled release of CO from a few selected photoCORMs under light illumination was shown to play a beneficial therapeutic role in cancer and bacterial infection . But the limited tissue penetration depth of UV‐vis light accompanied by the presence of phototoxicity would confine the clinical application of photoCORMs.…”

“…Benefiting from the protective characteristics of the matrix, bacteria implanted in biofilms are 1000 times more resistant to antibiotics than their planktonic counterparts . CORMs have been shown to attenuate the biofilm‐related infections due to the good ability to penetrate cell membranes . But the poor water solubility, the short half‐life of CO release and the rapid diffusion inevitably decreased the concentration of CO in target tissues, leading to low efficacy of antibacterial therapy .…”

Impact of Proinflammatory Cytokines on the Virulence of Uropathogenic Escherichia coli

“…The plate was left to dry overnight after 4 additional washes with RO-water. The crystal violet was then destained with 95% ethanol and the absorbance was quantified at 540 nm by spectrophotometry (Sahlberg Bang et al, 2016) (Multiskan Ascent, Thermo Labsystems, Helsinki, Finland). The data is presented as % of unstimulated CFT073.…”

Global gene expression profiling and antibiotic susceptibility after repeated exposure to the carbon monoxide-releasing molecule-2 (CORM-2) in multidrug-resistant ESBL-producing uropathogenic Escherichia coli

“…coli isolate 7 (ESBL7) and the non-ESBL-producing isolate UPEC2, were subjected to primary susceptibility testing through the disk diffusion method at the Department of Laboratory Medicine, Microbiology, Örebro University Hospital. ESBL7 was confirmed as ESBL-producing by detecting clavulanic acid reversible resistance for oxyiminocephalosporins and found to belong to the CTX-M-15 enzyme type and sequence type 131 [ 19 ]. ESBL7 showed resistance to cefotaxime (CTX), ceftazidime (CAZ), trimethoprim (TMP), ciprofloxacin (CIP) and mecillinam (MEL).…”