Flanagan, Lindsey, Steen, Rachel R, Saxby, Karinna, Klatter, Mirre, Aucott, Benjamin J, Winstanley, Craig ORCID: 0000-0002-2662-8053, Fairlamb, Ian JS, Lynam, Jason M, Parkin, Alison and Friman, Ville-Petri
(2018)
The Antimicrobial Activity of a Carbon Monoxide Releasing Molecule (EBOR-CORM-1) Is Shaped by Intraspecific Variation within <i>Pseudomonas aeruginosa</i> Populations.
FRONTIERS IN MICROBIOLOGY, 9 (FEB).
195-.
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The Antimicrobial Activity of a Carbon Monoxide Releasing Molecule (EBOR-CORM-1) Is Shaped by Intraspecific Variation within Pseudomonas aeruginosa Populations.pdf - Published version Download (1MB) |
Abstract
Carbon monoxide releasing molecules (CORMs) have been suggested as a new synthetic class of antimicrobials to treat bacterial infections. Here we utilized a novel EBOR-CORM-1 ([NEt<sub>4</sub>][MnBr<sub>2</sub>(CO)<sub>4</sub>]) capable of water-triggered CO-release, and tested its efficacy against a collection of clinical <i>Pseudomonas aeruginosa</i> strains that differ in infection-related virulence traits. We found that while EBOR-CORM-1 was effective in clearing planktonic and biofilm cells of <i>P. aeruginosa</i> strain PAO1 in a concentration dependent manner, this effect was less clear and varied considerably between different <i>P. aeruginosa</i> cystic fibrosis (CF) lung isolates. While a reduction in cell growth was observed after 8 h of CORM application, either no effect or even a slight increase in cell densities and the amount of biofilm was observed after 24 h. This variation could be partly explained by differences in bacterial virulence traits: while CF isolates showed attenuated <i>in vivo</i> virulence and growth compared to strain PAO1, they formed much more biofilm, which could have potentially protected them from the CORM. Even though no clear therapeutic benefits against a subset of isolates was observed in an <i>in vivo</i> wax moth acute infection model, EBOR-CORM-1 was more efficient at reducing the growth of CF isolate co-culture populations harboring intraspecific variation, in comparison with efficacy against more uniform single isolate culture populations. Together these results suggest that CORMs could be effective at controlling genetically diverse <i>P. aeruginosa</i> populations typical for natural chronic CF infections and that the potential benefits of some antibiotics might not be observed if tested only against clonal bacterial populations.
Item Type: | Article |
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Uncontrolled Keywords: | biofilms, carbon monoxide releasing molecules, CORM, cystic fibrosis, polymicrobial infections, Pseudomonas aeruginosa, synthetic chemistry, virulence |
Depositing User: | Symplectic Admin |
Date Deposited: | 14 Sep 2018 09:28 |
Last Modified: | 18 Oct 2023 10:35 |
DOI: | 10.3389/fmicb.2018.00195 |
Related URLs: | |
URI: | https://livrepository.liverpool.ac.uk/id/eprint/3018474 |