Antimicrobial and antibiofilm activity of human recombinant H1 histones against bacterial infections
Arévalo-Jaimes, Betsy Verónica (Universitat de Barcelona)
Salinas-Pena, Mónica (Molecular Biology Institute of Barcelona (IBMB-CSIC))
Ponte Marull, Immaculada (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Jordan, Albert (Molecular Biology Institute of Barcelona (IBMB-CSIC))
Roque Córdova, Alicia (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Torrents, Eduard (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Data:	2024
Descripció:	18 pàg.
Resum:	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 recombinant 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.
Ajuts:	Agencia Estatal de Investigación PID2021-125801OB-I00 Agencia Estatal de Investigación PLEC2022-009356 Agencia Estatal de Investigación PDC2022-133577-I00 Agencia Estatal de Investigación PID2020-112783GB-C21 Agencia Estatal de Investigación PID2020-112783GB-C22 Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-01545 "la Caixa" Foundation LCF/BQ/DI20/11780040
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Biofilm ; Galleria mellonella ; Treatment ; Toxicity ; Proteins ; Antimicrobial peptides
Publicat a:	mSystems, Vol. 9, Núm. 11 (November 2024) , ISSN 2379-5077

DOI: 10.1128/msystems.00704-24
PMID: 39470247

18 p, 2.3 MB

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