The Antimicrobial Activity of a Carbon Monoxide Releasing Molecule (EBOR-CORM-1) Is Shaped by Intraspecific Variation within <i>Pseudomonas aeruginosa</i> Populations



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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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
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