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Deciphering β-lactamase-independent β-lactam resistance evolution trajectories in Pseudomonas aeruginosa

Overview of attention for article published in Journal of Antimicrobial Chemotherapy (JAC), September 2018
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  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (90th percentile)
  • High Attention Score compared to outputs of the same age and source (83rd percentile)

Mentioned by

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38 tweeters

Citations

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1 Dimensions

Readers on

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18 Mendeley
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Title
Deciphering β-lactamase-independent β-lactam resistance evolution trajectories in Pseudomonas aeruginosa
Published in
Journal of Antimicrobial Chemotherapy (JAC), September 2018
DOI 10.1093/jac/dky364
Pubmed ID
Authors

Gabriel Cabot, Llorenç Florit-Mendoza, Irina Sánchez-Diener, Laura Zamorano, Antonio Oliver

Abstract

While resistance related to the expression of β-lactamases, such as AmpC from Pseudomonas aeruginosa, has been deeply studied, this work addresses the gap in the knowledge of other potential bacterial strategies to overcome the activity of β-lactams when β-lactamases are not expressed. We analysed β-lactam resistance evolution trajectories in a WT strain and in isogenic mutants either lacking AmpC (AmpC mutant) or unable to express it (AmpG mutant), exposed to increasing concentrations of ceftazidime for 7 days in quintuplicate experiments. Characterization of evolved lineages included susceptibility profiles, whole-genome sequences, resistance mechanisms, fitness (competitive growth assays) and virulence (Caenorhabditis elegans model). Development of resistance was faster for the WT strain but, after 7 days, all strains reached clinical ceftazidime resistance levels. The main resistance mechanism in the WT strain was ampC overexpression, due to mutations in dacB and ampD or mpl. In contrast, ampC overexpression did not evolve in any of the AmpG lineages. Moreover, sequencing of the ΔAmpC and ΔAmpG evolved lineages revealed alternative resistance mutations (not seen in WT lineages) that included, in all cases, large (50-600 kb) deletions of specific chromosomal regions together with mutations leading to β-lactam target [ftsI (PBP3)] modification and/or the overexpression or structural modification of the efflux pump MexAB-OprM. Finally, evolved lineages from the AmpC and, especially, AmpG mutants showed a reduced fitness and virulence. In addition to providing new insights into β-lactam resistance mechanisms and evolution, our findings should be helpful for guiding future strategies to combat P. aeruginosa infections.

Twitter Demographics

The data shown below were collected from the profiles of 38 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 18 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 18 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 4 22%
Student > Ph. D. Student 3 17%
Professor > Associate Professor 3 17%
Student > Doctoral Student 2 11%
Professor 1 6%
Other 5 28%
Readers by discipline Count As %
Medicine and Dentistry 6 33%
Immunology and Microbiology 5 28%
Biochemistry, Genetics and Molecular Biology 4 22%
Unspecified 2 11%
Veterinary Science and Veterinary Medicine 1 6%
Other 0 0%

Attention Score in Context

This research output has an Altmetric Attention Score of 24. 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 21 March 2019.
All research outputs
#641,225
of 13,104,802 outputs
Outputs from Journal of Antimicrobial Chemotherapy (JAC)
#245
of 5,522 outputs
Outputs of similar age
#24,178
of 264,147 outputs
Outputs of similar age from Journal of Antimicrobial Chemotherapy (JAC)
#20
of 123 outputs
Altmetric has tracked 13,104,802 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 95th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 5,522 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.4. This one has done particularly well, scoring higher than 95% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 264,147 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 90% of its contemporaries.
We're also able to compare this research output to 123 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 83% of its contemporaries.