The Antimicrobial Activity of a Carbon Monoxide Releasing Molecule (EBOR-CORM-1) Is Shaped by Intraspecific Variation within Pseudomonas aeruginosa Populations
Lindsey Flanagan, Rachel R. Steen, Karinna Saxby, Mirre Klatter, Benjamin J. Aucott, Craig Winstanley, Ian J. S. Fairlamb, Jason M. Lynam, Alison Parkin, Ville-Petri Friman
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 ([NEt4][MnBr2(CO)4]) capable of water-triggered CO-release, and tested its efficacy against a collection of clinicalPseudomonas aeruginosastrains that differ in infection-related virulence traits. We found that while EBOR-CORM-1 was effective in clearing planktonic and biofilm cells ofP. aeruginosastrain PAO1 in a concentration dependent manner, this effect was less clear and varied considerably between differentP. aeruginosacystic 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 attenuatedin vivovirulence 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 anin vivowax 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 diverseP. aeruginosapopulations 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.
Pharmacology, Toxicology and Pharmaceutical Science
1
3%
Immunology and Microbiology
1
3%
Other
3
9%
Unknown
11
32%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 24 February 2018.
All research outputs
#7,561,603
of 26,239,624 outputs
Outputs from Frontiers in Microbiology
#7,508
of 30,428 outputs
Outputs of similar age
#141,611
of 452,523 outputs
Outputs of similar age from Frontiers in Microbiology
#201
of 508 outputs
Altmetric has tracked 26,239,624 research outputs across all sources so far. This one has received more attention than most of these and is in the 71st percentile.
So far Altmetric has tracked 30,428 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.5. This one has gotten more attention than average, scoring higher than 74% of its peers.
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We're also able to compare this research output to 508 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 60% of its contemporaries.
