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Grant support

This study was partially supported by grants PID2021-125801OB-100, PLEC2022-009356, and PDC2022-133577-I00 to E.T., PID2020-112783GB-C21 to A.J., and PID2020-112783GB-C22 to A.R., funded by the Spanish Ministry of Science and Innovation MCIN/AEI/10.13039/501100011033 and "ERDF A way of making Europe," the CERCA programme and AGAUR-Generalitat de Catalunya (2021SGR01545), the European Regional Development Fund (FEDER), and Catalan Cystic Fibrosis association. The project that gave rise to these results received the support of a fellowship from "la Caixa" Foundation (ID 100010434). The fellowship code is "LCF/BQ/DI20/11780040."

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Salinas-Pena, MonicaAuthor

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November 12, 2024
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Antimicrobial and antibiofilm activity of human recombinant H1 histones against bacterial infections

Publicated to:Msystems. 9 (11): e00704-24- - 2024-11-19 9(11), DOI: 10.1128/msystems.00704-24

Authors: Arévalo-Jaimes, BV; Salinas-Pena, M; Ponte, I; Jordan, A; Roque, A; Torrents, E

Affiliations

Bacterial Infections: Antimicrobial Therapies. Institute for Bioengineering of Catalonia - Author
Barcelona Inst Sci & Technol, Inst Bioengn Catalonia IBEC, Bacterial Infect & Antimicrobial Therapies Grp, Barcelona, Spain - Author
Mol Biol Inst Barcelona IBMB CSIC, Barcelona, Spain - Author
Univ Autonoma Barcelona, Biochem & Mol Biol Dept, Barcelona, Spain - Author
Univ Barcelona, Fac Biol, Dept Genet Microbiol & Stat, Microbiol Sect, Barcelona, Spain - Author
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Abstract

Histones possess significant antimicrobial potential, yet their activity against biofilms remains underexplored. Moreover, concerns regarding adverse effects limit their clinical implementation. We investigated the antibacterial efficacy of human recombi nant histone H1 subtypes against Pseudomonas aeruginosa PAO1, both planktonic and in biofilms. After the in vitro tests, toxicity and efficacy were assessed in a P. aeruginosa PAO1 infection model using Galleria mellonella larvae. Histones were also evaluated in combination with ciprofloxacin (Cpx) and gentamicin (Gm). Our results demonstrate antimicrobial activity of all three histones against P. aeruginosa PAO1, with H1.0 and H1.4 showing efficacy at lower concentrations. The bactericidal effect was associated with a mechanism of membrane disruption. In vitro studies using static and dynamic models showed that H1.4 had antibiofilm potential by reducing cell biomass. Neither H1.0 nor H1.4 showed toxicity in G. mellonella larvae, and both increased larvae survival when infected with P. aeruginosa PAO1. Although in vitro synergism was observed between ciprofloxacin and H1.0, no improvement over the antibiotic alone was noted in vivo. Differences in antibacterial and antibiofilm activity were attributed to sequence and structural variations among histone subtypes. Moreover, the efficacy of H1.0 and H1.4 was influenced by the presence and strength of the extracellular matrix. These findings suggest histones hold promise for combating acute and chronic infections caused by pathogens such as P. aeruginosa.

Keywords

Antimicrobial peptideAntimicrobial peptidesBindingBiofilmGalleria mellonellaHost-defensePeptidProteinProteinsToxicityTreatment

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Msystems 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, 2024 there are still no calculated indicators, but in 2023, it was in position 34/163, thus managing to position itself as a Q1 (Primer Cuartil), in the category Microbiology.

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 2025-11-06:

  • 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: 5.
  • 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: 4 (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: 24.75.
  • The number of mentions on the social network X (formerly Twitter): 3 (Altmetric).
  • The number of mentions in news outlets: 3 (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:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.