{rfName}
Cr

Indexed in

APC

9 750,00 Euros

Citations

3

Altmetrics

Impact on the Sustainable Development Goals (SDGs)

Analysis of institutional authors

Zahia Inssaf, NedjariAuthorDabos, LauraCorresponding AuthorCouce, AlejandroCorresponding Author

Share

August 14, 2025
Publications
>
Article
No

Cryptic phenotypic variation emerges rapidly during the adaptive evolution of a carbapenemase

Publicated to: Nature Ecology & Evolution. - 2025-07-30 (), DOI: 10.1038/s41559-025-02804-6

Authors:

Dabos; L; Nedjari; I; Couce; A
[+]

Affiliations

CNRS, Paris, France - Author
Sorbonne Univ, Univ PSL, Univ Paris Cite, Lab Phys Ecole Normale Super, F-75005 Paris, France - Author
Univ Politecn Madrid, Ctr Biotecnol & Genomica Plantas, Madrid, Spain - Author
See more

Abstract

Interactions among beneficial mutations (that is, epistasis) are often strong enough to direct adaptation through alternative mutational paths. Although alternative solutions should display similar fitness under the primary selective conditions, their properties across secondary environments may differ widely. The extent to which these cryptic differences are to be expected is largely unknown, despite their importance-for example, in identifying exploitable collateral sensitivities among mutations conferring antibiotic resistance. Here we use directed evolution to characterize the diversity of mutational paths through which the prevalent carbapenemase Klebsiella pneumoniae carbapenemase-2 can evolve high activity against the clinically relevant antibiotic ceftazidime, an initially poor substrate. We identified 40 different substitutions-including many that are common in clinical settings-spread among 18 different mutational trajectories. Initial mutations determined four major groups into which the trajectories can be classified, a signature of strong epistasis. Despite similar final ceftazidime resistance, groups diverged markedly across multiple phenotypic dimensions, from molecular traits, such as in-cell stability and catalytic efficiency, to macroscopic traits, such as growth rate and activity against other beta-lactam antibiotics. Our results indicate that cryptic yet consequential phenotypic differences can accumulate rapidly under strong selection, unpredictably shaping the long-term success of resistance enzymes in their journey across hosts and environments.
[+]

Keywords

Antibiotic-resistanceBeta-lactamaseCeftazidime-avibactamDrug-resistanceFitnessKlebsiella-pneumoniaeMolecular population-geneticsMutationSensitivitSoft sweepsZero hunger

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Nature Ecology & Evolution due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2025, it was in position 2/200, thus managing to position itself as a Q1 (Primer Cuartil), in the category Ecology. Notably, the journal is positioned above the 90th percentile.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2026-04-25:

  • WoS: 1
  • Scopus: 2
[+]

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2026-04-25:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 8.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 8 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 6.
  • The number of mentions on the social network X (formerly Twitter): 4 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • Assignment of a Handle/URN as an identifier within the deposit in the Institutional Repository: https://oa.upm.es/93353/

As a result of the publication of the work in the institutional repository, statistical usage data has been obtained that reflects its impact. In terms of dissemination, we can state that, as of

  • Views: 36
  • Downloads: 10
Continuing with the social impact of the work, it is important to emphasize that, due to its content, it can be assigned to the area of interest of ODS 2 - End hunger, achieve food security and improved nutrition and promote sustainable agriculture, with a probability of 50% according to the mBERT algorithm developed by Aurora University.
[+]

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: France.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (DABOS, MARIA LAURA BELEN) and Last Author (COUCE IGLESIAS, ALEJANDRO).

the authors responsible for correspondence tasks have been DABOS, MARIA LAURA BELEN and COUCE IGLESIAS, ALEJANDRO.

[+]

Awards linked to the item

We thank L. J. Gonzalez and A. J. Vila for valuable experimental suggestions and J. Barber and L. Lopez-Merino for proofreading the manuscript. L.D. acknowledges support from the European Commission under the Horizon 2020 Framework Programme (Marie Sklodowska-Curie Individual Fellowship 101029953). A.C. acknowledges support from the Agencia Estatal de Investigacion (Proyectos de Investigacion, Desarrollo e Innovacion (PID2019-110992GA-I00 and PID2022-142857NB-I00) and Centros de Excelencia Severo Ochoa (SEV-2016-0672 and CEX2020-000999-S)) and a Comunidad de Madrid Talento Fellowship (2019-T1/BIO-12882 and 2023-5A/BIO-28940).
[+]